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Aims The atherosclerotic profile and advanced plaque subtype burden in symptomatic patients ≤45 years old have not been established. This study aimed to assess the prevalence and predictors of coronary artery calcium (CAC), plaque subtypes, and plaque burden by coronary computed tomography angiography (CCTA) in symptomatic young patients. Methods and results We included 907 symptomatic young patients (18–45 years) from Montefiore undergoing CCTA for chest pain evaluation. Prevalence and predictors of CAC, plaque subtypes, and burden were evaluated using semi-automated software. In the overall population (55% female and 44% Hispanic), 89% had CAC = 0. The likelihood of CAC or any plaque by CCTA increased with >3 risk factors {RFs, odds ratio [OR] 7.13 (2.14–23.7) and OR 10.26 (3.36–31.2), respectively}. Any plaque by CCTA was present in 137 (15%); the strongest independent predictors were age ≥35 years [OR 3.62 (2.05–6.41)] and family history of premature coronary artery disease (FHx) [OR 2.76 (1.67–4.58)]. Stenosis ≥50% was rare (1.8%), with 31% of those having CAC = 0. Significant non-calcified plaque (NCP, 37.2%) and low-attenuation plaque (LAP, 4.24%) burdens were seen, even in those with non-obstructive stenosis. Among patients with CAC = 0, 5% had plaque, and the only predictor of exclusively NCP was FHx [OR 2.29 (1.08–4.86)]. Conclusion In symptomatic young patients undergoing CCTA, the prevalence of CAC or any coronary atherosclerosis was not negligible, and the likelihood increased with RF burden. The presence of coronary stenosis ≥50% was rare and most often accompanied by CAC >0, but there was a significant burden of NCP and LAP even within the non-obstructive group. [ABSTRACT FROM AUTHOR]

Summary: We evaluated the relationship of bone mineral density (BMD) by computed tomography (CT), to predict fractures in a multi-ethnic population. We demonstrated that vertebral and hip fractures were more likely in those patients with low BMD. This is one of the first studies to demonstrate that CT BMD derived from thoracic vertebrae can predict future hip and vertebral fractures. Purpose/Introduction: Osteoporosis affects an enormous number of patients, of all races and both sexes, and its prevalence increases as the population ages. Few studies have evaluated the association between the vertebral trabecular bone mineral density(vBMD) and osteoporosis-related hip fracture in a multiethnic population, and no studies have demonstrated the predictive value of vBMD for fractures. Method: We sought to determine the predictive value of QCT-based trabecular vBMD of thoracic vertebrae derived from coronary artery calcium scan for hip fractures in the Multi-Ethnic Study of Atherosclerosis(MESA), a nationwide multicenter cohort included 6814 people from six medical centers across the USA and assess if low bone density by QCT can predict future fractures. Measures were done using trabecular bone measures, adjusted for individual patients, from three consecutive thoracic vertebrae (BDI Inc, Manhattan Beach CA, USA) from non-contrast cardiac CT scans. Results: Six thousand eight hundred fourteen MESA baseline participants were included with a mean age of 62.2 ± 10.2 years, and 52.8% were women. The mean thoracic BMD is 162.6 ± 46.8 mg/cm3 (95% CI 161.5, 163.7), and 27.6% of participants (n = 1883) had osteoporosis (T-score 2.5 or lower). Over a median follow-up of 17.4 years, Caucasians have a higher rate of vertebral fractures (6.9%), followed by Blacks (4.4%), Hispanics (3.7%), and Chinese (3.0%). Hip fracture patients had a lower baseline vBMD as measured by QCT than the non-hip fracture group by 13.6 mg/cm3 [P < 0.001]. The same pattern was seen in the vertebral fracture population, where the mean BMD was substantially lower 18.3 mg/cm3 [P < 0.001] than in the non-vertebral fracture population. Notably, the above substantial relationship was unaffected by age, gender, race, BMI, hypertension, current smoking, medication use, or activity. Patients with low trabecular BMD of thoracic vertebrae showed a 1.57-fold greater risk of first hip fracture (HR 1.57, 95% CI 1.38–1.95) and a nearly threefold increased risk of first vertebral fracture (HR 2.93, 95% CI 1.87–4.59) compared to normal BMD patients. Conclusion: There is significant correlation between thoracic trabecular BMD and the incidence of future hip and vertebral fracture. This study demonstrates that thoracic vertebrae BMD, as measured on cardiac CT (QCT), can predict both hip and vertebral fractures without additional radiation, scanning, or patient burden. Osteopenia and osteoporosis are markedly underdiagnosed. Finding occult disease affords the opportunity to treat the millions of people undergoing CT scans every year for other indications. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic endocrine disorder that affects more than 20 million people in the United States. DM-related complications affect multiple organ systems and are a significant cause of morbidity and mortality among people with DM. Of the numerous acute and chronic complications, atherosclerosis due to diabetic dyslipidemia is a condition that can lead to many life-threatening diseases, such as stroke, coronary artery disease, and myocardial infarction. The nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway is an emerging antioxidative pathway and a promising target for the treatment of DM and its complications. This review aims to explore the Nrf2 pathway's role in combating diabetic dyslipidemia. We will explore risk factors for diabetic dyslipidemia at a cellular level and aim to elucidate how the Nrf2 pathway becomes a potential therapeutic target for DM-related atherosclerosis. [ABSTRACT FROM AUTHOR]

Summary: Objective: This study sought to systematically compare the efficacy and mechanism of cyclodextrins as drug interventions in lipid metabolism diseases, potentially providing ideas for subsequent research directions and clinical applications. Methods: We used the bibliometric method for feature mining, applied VOSviewer software for clustering analysis, and applied content analysis for objective descriptions and accurate analysis. Results: (1) We collected more than 50 studies, which is the basic database of this study. (2) The academic bubble map showed that this research area was popular in the United States. (3) Cluster analysis showed that the intensively studied diseases in this field were Niemann–Pick type C (NPC), atherosclerosis (AS), and obesity. The hot‐spot cyclodextrin types were HP‐β‐CD. (4) Literature measurement revealed the involvement of 15 types of lipid metabolism diseases. Among them, NPC, diabetes, and obesity were studied in clinical trials. Dyslipidemia and AS have been reported relatively more frequently in animal experiments. The studies of cellular experiments provide insight into the molecular mechanisms that intervene in lipid metabolism diseases from multiple perspectives. The exploration of the molecular mechanisms by which cyclodextrins exert their pharmacological effects mainly revolves around lipid metabolism. Conclusion: It is worthwhile to investigate the role and mechanism of cyclodextrins in other lipid metabolism diseases. The potential efficacy evaluation of cyclodextrins as pharmaceutical drugs for oral or injectable formulations is less studied and may become a new focus in the future. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease (CVD) such as myocardial infarction and stroke. CVD in patients with IBD might occur in those with younger age and active disease, which are not traditional risk factors of CVD. Atherosclerotic CVD (ASCVD) and IBD are both proinflammatory conditions, and the underlying chronic inflammation might drive ASCVD risk. Decreasing inflammation might reduce this risk; however, data are limited. IBD medications can increase or decrease ASCVD risk. There are no specific guidelines or modalities to assess ASCVD in IBD. Early detection and risk stratification strategies have been established in other chronic inflammatory disorders. This article discusses causes of CVD in IBD and strategies to modify the consequences. [ABSTRACT FROM AUTHOR]

BACKGROUND: In contrast to fine particles, less is known of the inflammatory and coagulation impacts of coarse particulate matter (PM10-2.5, particulate matter with aerodynamic diameter ≤10μm and>2.5μm). Toxicological research suggests that these pathways might be important processes by which PM10-2.5 impacts health, but there are relatively few epidemiological studies due to a lack of a national PM10-2.5 monitoring network. OBJECTIVES: We used new spatiotemporal exposure models to examine associations of both 1-y and 1-month average PM10-2.5 concentrations with markers of inflammation and coagulation. METHODS: We leveraged data from 7,071 Multi-Ethnic Study of Atherosclerosis and ancillary study participants 45-84 y of age who had repeated plasma measures of inflammatory and coagulation biomarkers. We estimated PM10-2.5 at participant addresses 1 y and 1 month before each of up to four exams (2000-2012) using spatiotemporal models that incorporated satellite, regulatory monitoring, and local geographic data and accounted for spatial correlation. We used random effects models to estimate associations with interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, and D-dimer, controlling for potential confounders. RESULTS: Increases in PM10-2.5 were not associated with greater levels of inflammation or coagulation. A 10-μg/m³] increase in annual average PM10-2.5was associated with a 2.5% decrease in CRP [95% confidence interval (CI): -5.5, 0.6]. We saw no association between annual average PM10-2.5 and the other markers (IL-6: -0.7%, 95% CI: -2.6, 1.2; fibrinogen: -0.3%, 95% CI: -0.9, 0.3; D-dimer: -0.2%, 95% CI: -2.6, 2.4). Associations consistently showed that a 10-μg/m³ increase in 1-month average PM10-2.5 was associated with reduced inflammation and coagulation, though none were distinguishable from no association (IL-6: -1.2%, 95% CI: -3.0, 0.5; CRP: -2.5%, 95% CI: -5.3, 0.4; fibrinogen: -0.4%, 95% CI: -1.0, 0.1; D-dimer: -2.0%, 95% CI: -4.3, 0.3). DISCUSSION: We found no evidence that PM10-2.5 is associated with higher inflammation or coagulation levels. More research is needed to determine whether the inflammation and coagulation pathways are as important in explaining observed PM10-2.5 health impacts in humans as they have been shown to be in toxicology studies or whether PM10-2.5 might impact human health through alternative biological mechanisms. [ABSTRACT FROM AUTHOR]

We utilized the comprehensive sleep assessment of the Multi-Ethnic Study of Atherosclerosis (2010–2013), a cohort of US White, Black, Chinese, and Hispanic adults and older adults (n  = 1,736; mean age = 68.3 years), to draw 13 sleep dimensions and create composite Sleep Health Scores to quantify multidimensional sleep health disparities. After age and sex adjustment in linear regression, compared with White participants, Black participants showed the greatest global sleep disparity, followed by Hispanic and Chinese participants. We estimated relative "risk" (RR) of obtaining favorable sleep compared with White adults at the component level according to race/ethnicity (lower is worse). The largest disparities were in objectively measured sleep timing regularity (RRBlack = 0.37, 95% confidence interval (CI): 0.29, 0.47; RRHispanic = 0.64, 95% CI: 0.52, 0.78; RRChinese = 0.70, 95% CI: 0.54, 0.90) and duration regularity (RRBlack = 0.55, 95% CI: 0.47, 0.65; RRHispanic = 0.76, 95% CI: 0.66, 0.88; RRChinese = 0.74, 95% CI: 0.61, 0.90) after sex and age adjustment. Disparities in duration and continuity were also apparent, and Black adults were additionally disadvantaged in % slow-wave sleep (N3), sleepiness, and sleep timing (24-hour placement). Sleep timing regularity, duration regularity, duration, and continuity may comprise a multidimensional cluster of targets to reduce racial/ethnic sleep disparities. [ABSTRACT FROM AUTHOR]

Guidelines developed by the American College of Cardiology/American Heart Association (ACC/AHA) recommend lipid-lowering therapies (LLTs) to reduce low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. This study described LLT utilization patterns and LDL-C goal achievement (to <70 mg/dL) among patients with ASCVD in the United States. This retrospective study was conducted using Optum's de-identified Clinformatics Data Mart Database (CDM). Patients with their first ASCVD diagnosis (index date) in the CDM database between July 1, 2015, and December 31, 2018, were followed for ≥12 months to assess LLT utilization patterns and change in LDL-C. LLTs included were statins and non-statin LLTs (ezetimibe, fibrates, and proprotein convertase subtilisin/kexin type 9 inhibitors). Adherence was measured as the proportion of days covered (PDC), defined as the number of days with drug on-hand (or number of days exposed to drug) divided by the 12-month follow-up period. Patients with PDC ≥0.8 were considered adherent. Among the patients with ASCVD (N = 1,424,893) included in this study, only 621,978 (43.7%) had at least one LDL-C measurement at baseline (6 months prior to and 3 months after the index date). The mean age was 71.5 years, and almost half of the patients were female. Patients were followed for a mean (standard deviation [SD]) duration of 30.6 (11.4) months (median of 29.9 months). During the follow-up, about one-quarter of the patients did not receive any LLT. Among treated patients, 89.5% received statins and 10.5% received non-statin LLT. Less than half (47.6%) of the patients were adherent to the index treatment during the 12-month follow-up. Even in patients receiving combination therapy (statin + non-statin LLT), a sizable proportion (35.8%) showed an increase in LDL-C over the follow-up period. This retrospective study highlighted limited LDL-C monitoring in patients with ASCVD, and unmet need in terms of suboptimal utilization of non-stain LLTs, limited adherence to LLTs, and inadequate lipid control after treatment (among those with LDL-C measurements during the follow-up period) need to be addressed to improve outcomes in this patient cohort. International societies of cardiologists recommend use of medications to lower the "bad" cholesterol, and its risk of cardiovascular diseases like stroke. We aimed to describe how those medications are being used and to what extent patients with cardiovascular diseases in the United States have their "bad" cholesterol under control. Results of this study indicate that cholesterol check-up among the patients was limited. Among recommended medications, statins were mostly used, whereas use of other recently approved medications was minimal. One-quarter of patients were not prescribed medications to control their cholesterol. Moreover, patients were not taking the medications as frequently as prescribed. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that periodontal disease (PD) was associated with an increased risk for cardiovascular diseases (CVD), although evidence is inconclusive. Purpose: We first sought to prospectively evaluate the relationship of PD to CVD and all -cause mortality using a national representative sample in the United States. Methods: A prospective study was carried out of 147 patients with a periodontal disease who referred for periodontal consultation. The severity of PD was categorized as non-PD, modest and severe PD based on clinical attachment loss and pocket depth. Results: The levels of inflammation markers (high sensitivity C-reactive protein, white cell count and fibrinogen) were significantly higher in men with severe PD compared to men without PD (p < 0.05). The prospective associations were evaluated using multivariable Cox proportional - hazards models. After adjusting for age, gender, household income and traditional risk factors of CVD, severe PD was associated with an increase risk of CVD mortality and all-cause mortality in men aged 30-64 years (HR = 2.13 with 95% confidence interval of 1.37-3.31 for CVD mortality; HR = 1.64 with 95% confidence interval of 1.25-2.15 for all-cause mortality). In addition, significant linear trends were found in CVD and all-cause mortality across the severity of PD (p < 0.001). However, no significant associations were found in men aged ≥65 and in women. Conclusions: There appears to be prospective associations between PD and CVD and all-cause mortality in men aged 30-64 years. Inflammation may be one possible pathway to link PD with CVD. [ABSTRACT FROM AUTHOR]

South Asians face stressors as a growing immigrant group in America. Work is needed to understand how these stressors impact mental health to identify those at risk of depression and design interventions. This study examined associations of three stressors (discrimination, low social support, limited English proficiency) with depressive symptoms in South Asians. Using cross-sectional data from the Mediators of Atherosclerosis in South Asians Living in America study (N = 887), we fit logistic regression models to evaluate independent/joint effects of three stressors on depression. Overall prevalence of depression was 14.8%; 69.2% of those with all three stressors had depression. The combined effect of high discrimination/low social support was significantly greater than the sum of the individual factors. Experiences of discrimination, low social support, or limited English proficiency, as well as a combination of these factors, should be considered when diagnosing/treating South Asian immigrants in a culturally appropriate manner. [ABSTRACT FROM AUTHOR]

• Among adults 40–75 years of age eligible for statins for primary prevention based on 10-year risk, rates of statin utilization by age are unknown. • Statin use for primary prevention is lower among US adults <65 vs. 65–75 years of age, despite similar predicted 10-year ASCVD risk and a higher burden risk factors. • Adults <65 years are treated less aggressively with statin therapy, leaving this population exposed to greater risk for future ASCVD events. Statin use among younger adults at high atherosclerotic cardiovascular disease (ASCVD) risk compared with older adults at the same risk is unclear. We determined prevalent statin use by 10-year ASCVD risk and age among US participants aged 40–75 eligible for risk-indicated primary prevention statins from the 2013–2020 National Health and Nutrition Examination Survey cycles. Among 3,503 participants, statin use by ASCVD risk (5-<7.5%, 7.5-<20%, and ≥20%) was 9.4%, 9.0%, and 12.2% among those age 40–54 compared to 22.0%, 23.9%, and 14.3% among adults 55–64 years and 39.3%, 33.6%, and 38.1% age 65–75 years. After adjusting for sociodemographic and healthcare access, the prevalence ratio (vs. 65–75 years) for statin use among adults with an ASCVD risk of 7.5-<20% age 40–54 years was 0.40 (95% confidence interval [CI] 0.39,0.41) and 0.87 (95% CI 0.87,0.88) for adults 55–64 years. Among high ASCVD-risk adults aged 40–75 years, primary prevention statin use was lower among adults <65 years despite similar ASCVD risk as older adults. [ABSTRACT FROM AUTHOR]

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In a nationally representative population-based study of US adults, the authors sought to examine the association between body mass index (BMI) and all-cause and cardiovascular disease (CVD) mortality in a nationally representative sample of adults with and without atherosclerotic cardiovascular disease (ASCVD), and further stratified by age, sex, and race/ethnicity. The study used data from 2006 to 2015 National Health Interview Survey and categorized participants into the following BMI categories: normal weight (20–24.9), overweight (25–29.9), obesity class 1 (30–34.9), obesity class 2 (35–39.9), and obesity class 3 (≥40 kg/m2). Multivariable Cox proportional hazards models were used to assess the risk of all-cause and CVD mortality across successively increasing BMI categories overall, and by sociodemographic subgroups. A total of 210,923 individuals were included in the final analysis. In the population without ASCVD, the risk of all-cause and CVD mortality was lower in overweight and higher in obesity classes 2 and 3, compared with normal weight, with the highest risk observed in the young adult (age 18–39) population. Elderly adults (65 and above) and populations with ASCVD exhibited a BMI-mortality paradox. In addition, Hispanic individuals did not show a relationship between BMI and mortality compared with non-Hispanic White and Black adults. In conclusion, being overweight was associated with decreased risk, whereas obesity class 3 was consistently associated with increased risk of all-cause and CVD mortality in adults without ASCVD, particularly young adults. BMI-mortality paradox was noted in ASCVD, elderly, and non-Hispanic adults. [ABSTRACT FROM AUTHOR]

Background: The contemporary uptake of lipid‐lowering therapies (LLT), including more intensive treatment with high‐intensity statins and non‐statin LLT, among U.S. older adults (≥75 years old) with ASCVD is unknown. Methods: In this multicenter retrospective cohort study of a large geographically diverse sample of commercially insured U.S. older adults with ASCVD, we assessed treatment with LLT. Secondary measures included LDL‐C above target ≥70 mg/dl, persistence and adherence to therapy. Results: Treatment with statins, high‐intensity statins, ezetimibe, and PCSK9 inhibitors was assessed in 194,503 older adults (49.9% female) with known ASCVD on January 31st, 2019. 49.3% of older adults with ASCVD were on any statin, with 16.6% receiving a high‐intensity statin and 32.7% on low‐or moderate‐intensity statins. Treatment with ezetimibe (2.4%) or PCSK9 inhibitors (0.24%) was rare and 62.6% of the overall cohort had an LDL‐C above target at ≥70 mg/dl. Patients on high‐intensity statins were more frequently male, had a diagnosis of coronary artery disease, and were more frequently seen by a cardiologist compared with those on low‐or moderate‐intensity statins and untreated individuals (p < 0.0001). The majority of older adults on high‐intensity statins remained on therapy at 12 months (91.9%) and 85.7% had ≥75% adherence to treatment. Conclusions: Less than half of eligible older adults with ASCVD are on statins and only a minority of patients are receiving more intensive lipid‐lowering to improve outcomes. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque. Such distinct phenotypes reflect different pathophysiologic pathways and are associated with different risks for acute ischemic events. Noninvasive coronary imaging techniques, such as computed tomography, positron emission tomography, and coronary magnetic resonance imaging, have major potential to accelerate cardiovascular drug development, which has been affected by the high costs and protracted timelines of cardiovascular outcome trials. This may be achieved through enrichment of high-risk phenotypes with higher event rates or as primary end points of drug efficacy, at least in phase 2 trials, in a manner historically performed through intravascular coronary imaging studies. Herein, we provide a comprehensive review of the current technology available and its application in clinical trials, including implications for sample size requirements, as well as potential limitations. In its effort to accelerate drug development, the US Food and Drug Administration has approved surrogate end points for 120 conditions, but not for CAD. There are robust data showing the beneficial effects of drugs, including statins, on CAD progression and plaque stabilization in a manner that correlates with established clinical end points of mortality and major adverse cardiovascular events. This, together with a clear mechanistic rationale for using imaging as a surrogate CAD end point, makes it timely for CAD imaging end points to be considered. We discuss the importance of global consensus on these imaging end points and protocols and partnership with regulatory bodies to build a more informed, sustainable staged pathway for novel therapies. [ABSTRACT FROM AUTHOR]

Arterial stiffness, echolucency and texture features are altered with hypertension and associated with increased cardiovascular disease risk. The relationship between these markers and structural and load-dependent artery wall changes in hypertension are poorly understood. The Multi-ethnic Study of Atherosclerosis (MESA) is a longitudinal study of 6814 adults from six communities across the United States designed to study subclinical cardiovascular disease. From B-mode imaging of the right common carotid artery at the baseline MESA examination, we calculated carotid artery Young's elastic modulus (YEM, n = 5894) and carotid artery gray-scale texture features (n = 1403). The standard YEM calculation represented total arterial stiffness. Structural stiffness was calculated by adjusting YEM to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. We found that load-dependent YEM was elevated in hypertensive individuals compared with normotensive individuals (35.7 ± 105.5 vs. -62.0 ± 112.4 kPa, p < 0.001) but that structural YEM was similar (425.3 ± 274.8 vs. 428.4 ± 293.0 kPa, p = 0.60). Gray-scale measures of heterogeneity in carotid artery wall texture (gray-level difference statistic contrast) had small but statistically signification correlations with carotid artery stiffness mechanisms. This association was positive for structural YEM (0.107, p < 0.001), while for load-dependent YEM, the association was negative (-0.064, p = 0.02). In conclusion, increased arterial stiffness in hypertension was owing solely to the non-linear mechanics of having higher blood pressure, not structural changes in the artery wall, and high load-dependent stiffness was associated with a more homogenous carotid artery wall texture. This is potentially related to arterial remodeling associated with subclinical atherosclerosis and future cardiovascular disease development. These results also indicate that gray-scale texture features from ultrasound imaging had a small but statistically significant association with load-dependent arterial stiffness and that gray-scale texture features may be partially load dependent. [ABSTRACT FROM AUTHOR]

• Non-statin lipid-lowering therapies reduce residual ASCVD risk. • Utilization of non-statin therapies is low for secondary prevention. • There has been limited uptake of non-statin therapies in the last several years. • Increasing use of these therapies is paramount to improving the treatment gap. Nearly two-thirds of individuals with atherosclerotic cardiovascular disease (ASCVD) do not reach target low-density lipoprotein cholesterol despite statin therapy. Three novel lipid-lowering therapies have proven to further reduce ASCVD beyond statins, including: ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), and icosapent ethyl. This study evaluated the use of these three agents in 728,423 individuals with ASCVD from 89 US health systems from 01/2018 through 03/2021 using the electronic health record. As of 2021, only 6.0% of ASCVD patients were on ezetimibe, 1.6% were on a PCSK9i, and 1.3% on icosapent ethyl, with utilization only marginally increasing over the study period. Addressing the underutilization of non-statin lipid-lowering therapy for secondary prevention is a critical step in improving the treatment gap of patients with residual risk of ASCVD. [ABSTRACT FROM AUTHOR]

Background: Inclisiran is a novel, cholesterol-lowering therapy, with a long duration of effect, administered every 6 months (subcutaneously by a healthcare professional). In the ORION-10 trial in US patients with atherosclerotic cardiovascular disease (ASCVD) in addition to maximum tolerated statins, with or without ezetimibe, inclisiran demonstrated statistically significant reductions in low-density lipoprotein cholesterol (LDL-C) of up to 51%. This is the first peer-reviewed publication to investigate the price at which inclisiran is cost effective in the US. Objective: The aim of this study was to determine the maximum price at which inclisiran is cost effective in addition to standard of care, in US patients with ASCVD, versus standard of care alone, at different willingness-to-pay thresholds. Design, Setting and Participants: A lifetime Markov model from the US health system perspective, including 15 health states, was used to evaluate the cost effectiveness of inclisiran. The following states were separated by time from a previous cardiovascular event (0–1 years, 1–2 years, 2+ years ['stable']): initial, unstable angina, myocardial infarction, and stroke. Additional states included revascularization and death (cardiovascular or non-cardiovascular causes). Baseline risk of cardivoascular events were from US database sources or published literature. Reductions in LDL-C from inclisiran were from the ORION-10 trial. LDL-C reduction was used to adjust baseline risk of cardiovascular events, based on established relationships between 1 mmol/L reduction in LDL-C and decreases in cardiovascular events, from the Cholesterol Treatment Trialists studies. The population included adults with a history of ASCVD, and LDL-C ≥ 70 mg/dL, despite maximum tolerated doses of statin therapy. Interventions: Inclisiran as an adjunct to standard of care, compared with standard of care alone. Main Outcomes and Measures: The threshold price of inclisiran. Results: Inclisiran as an adjunct to standard of care resulted in threshold annual inclisiran prices of $6383, $9973, and $13,563 at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per quality-adjusted life-year, respectively. Probabilistic sensitivity analysis showed that at a threshold of $100,000 per QALY, inclisiran had a 100% probability of being cost effective, with an annual price below $9000. At the publicly available price of $3250 per dose, inclisiran was found to have an incremental cost-effectiveness ratio just above the $50,000 per QALY threshold, of $51,686. Conclusions and Relevance: This study identified the price at which inclisiran is cost effective for the US health system, at generally accepted willingness-to-pay thresholds. [ABSTRACT FROM AUTHOR]

While recent decades have seen substantial reductions in cardiovascular mortality, heart disease remains the number one cause of death both in the United States and globally. This has led many to advocate for prescribing statins even more widely, including to patients with low risk of cardiovascular disease, based on the hypothesis that any reduction in lipid levels will eventually translate to a reduction in the development of atherosclerosis and thus to subsequent mortality. However, empirical evidence to date has not substantiated the hoped for benefits of this strategy. When healthy patients without cardiovascular disease are prescribed statins they do not live longer, and they have only a marginal reduction in the risk of ischemic events. Furthermore, statins cause numerous side effects which substantially limit their net benefit. These tradeoffs are even more lopsided in elderly patients treated for primary prevention, in whom statin therapy does not lead to a reduction in mortality or ischemic events and has the potential for significant harms. Strategies to reduce the risk of cardiovascular disease should therefore avoid a focus on cholesterol levels and subsequent pharmacological therapy and should instead redouble efforts to improve the lifestyle factors that are far more consequential to the development of cardiovascular disease and overall good health. • Statins for primary prevention do not improve survival and leads to small reductions in events. • Statins have significant adverse effects that outweigh these small benefits. • Elderly patients see no benefit and have an even greater risk of harm. • The emphasis on statins shifts focus away the more important healthy eating and physical activity. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a multifactorial, lipoprotein-driven condition that leads to plaque formation within the arterial tree, leading to subsequent arterial stenosis and thrombosis that accounts for a large burden of cardiovascular morbidity and mortality globally. Atherosclerosis of the lower extremities is called peripheral artery disease and is a major cause of loss in mobility, amputation, and critical limb ischemia. Peripheral artery disease is a common condition with a gamut of clinical manifestations that affects an estimated 10 million people in the United States of America and 200 million people worldwide. The role of apolipoprotein B-containing lipoproteins, such as LDL and remnant lipoproteins in the development and progression of atherosclerosis, is well-established. The focus of this paper is to review existing data on lipid-lowering therapies in lower extremity atherosclerotic peripheral artery disease. [ABSTRACT FROM AUTHOR]

Background: Despite guidelines recommending the evaluation of adverse pregnancy outcomes (APOs) as a part of the atherosclerotic cardiovascular disease (ASCVD) risk assessment in women, there is limited awareness of this issue in health care professionals. We sought to evaluate the extent of this gap in knowledge. Methods: An online study using a standardized questionnaire was advertised through newsletters and websites of professional organizations. After a low response rate, the link to the survey was announced on Twitter and via personal email invitations. Differences between groups of respondents were evaluated with z-tests of proportion. Results: Out of 446 complete responses, there were 315 cardiologists and 112 obstetricians and gynecologists (OBGyns). There was an >90% awareness of association of adverse maternal outcomes with gestational hypertension and gestational diabetes with ASCVD, but only <60% awareness of association of adverse maternal outcomes with preterm birth. There were significant differences in ASCVD risk assessment and awareness of the association of APOs with adverse outcomes between cardiologists and OBGyns, and between female and male cardiologists. A greater proportion of female cardiologists thought that the guidelines recommended annual follow-up for high-risk women. Conversely, a greater proportion of male cardiologists were unsure of the frequency of follow-up of such women in the relevant guidelines. A higher proportion of U.K. respondents thought that women with high-risk pregnancies should never be screened for cardiovascular disease postpartum compared with U.S. respondents. Conclusions: In a self-selected group of health care professionals interested in women's cardiovascular health, there remains a large gap in knowledge and awareness of the association of APOs with ASCVD risk, in particular, a lack of awareness of the association of ASCVD risk with preterm delivery. Specific target groups for improving knowledge regarding these sex-specific risk enhancers include male cardiologists and health care professionals practicing in the United Kingdom. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is one of the greatest public health concerns and is the leading cause of morbidity and mortality in the United States and worldwide. CVD is a broad yet complex term referring to numerous heart and vascular conditions, all with varying pathologies. Macrophages are one of the key factors in the development of these conditions. Macrophages play diverse roles in the maintenance of cardiovascular homeostasis, and an imbalance of these mechanisms contributes to the development of CVD. In the current review, we provide an in-depth analysis of the diversity of macrophages, their roles in maintaining tissue homeostasis within the heart and vasculature, and the mechanisms through which imbalances in homeostasis may lead to CVD. Through this review, we aim to highlight the potential importance of macrophages in the identification of preventative, diagnostic, and therapeutic strategies for patients with CVD. [ABSTRACT FROM AUTHOR]

Background: Despite significant morbidity and mortality related to atherosclerotic cardiovascular disease, to date, most major clinical trials studying the effects of statin therapy have excluded older adults. The objective of this analysis was to evaluate the effect of initiating statin therapy on incident dementia and mortality among individuals 75 years of age or older across the complete spectrum of kidney function., Methods: We conducted a retrospective cohort study of 640,191 VA health system patients who turned 75 years of age between 2000 and 2018. Patients on statin therapy received the medication for an average of 6.3 years (standard deviation 4.6 years). The primary outcome of interest included incident dementia diagnosis during the study period. The secondary outcome was all-cause mortality. Cox proportional hazard analysis was used to evaluate the adjusted association of statin initiation with these outcomes., Results: There was a higher rate of incident dementia in the No Statin group (4.7%) vs the Statin group (3.2%). Additionally, we observed a 22% all-cause mortality benefit associated with statin therapy. We did not observe a treatment effect with respect to primary or secondary outcomes across varying levels of kidney function., Conclusion: This large cohort study did not reveal an association between the initiation of statin therapy and incident dementia. A survival benefit was seen in statin users compared with nonusers. Prospective studies in more diverse populations including older adults will be needed to verify these findings., (Copyright © 2024. Published by Elsevier Inc.)

Background: The aim of this study was to assess how early-adulthood body mass index (BMI) and waist circumference (WC) relate to long-term cardiovascular structure, function, and prognosis in individuals without obesity and with low cardiovascular risk factor (CVRF) burden., Methods and Results: A total of 2024 participants aged 18 to 30 from the CARDIA (Coronary Artery Risk Development in Young Adults) study, without obesity and with low CVRFs defined as the absence of cardiovascular disease (CVD), diabetes, hypertension, current smoking, and dyslipidemia were included. A CVRF-optimal subgroup was also defined, with blood pressure<120/80 mm Hg, fasting glucose <100 mg/dL, total cholesterol <200, low-density lipoprotein cholesterol <130, and women with high-density lipoprotein cholesterol ≥50 mg/dL. Coronary artery calcification, carotid intima-media thickness, left ventricular mass, left ventricular ejection fraction, longitudinal peak systolic strain, and diastolic function were assessed in midlife. Cox regression was used to calculate hazard ratios of BMI and WC for all-cause death and CVD events. Logistic regression was used to estimate odds ratios for subclinical CVD. Over 33.9 years (median follow-up), 5.2% (n=105) died, and 2.6% (n=52) had CVD events. Each 1-SD BMI increase was associated with 27% (95% CI, 1.10-1.47), 24% (1.08-1.43), 42% (1.20-1.68), 28% (1.05-1.57), 51% (1.20-1.90), and 49% (1.10-2.02) higher odds of coronary artery calcification presence, increased carotid intima-media thickness, left ventricular hypertrophy, reduced left ventricular ejection fraction, low longitudinal peak systolic strain, and diastolic dysfunction, respectively, in the CVRF-low group. Generally, similar associations were found for WC and in the CVRF-optimal subgroup. No significant associations between BMI and WC with CVD and death were found., Conclusions: Elevations in BMI and WC among young low-risk individuals, even within the nonobesity range, are associated with midlife cardiovascular health.

Background and Aim: Long-term associations between the alternative healthy eating index (AHEI) score and two predictive indicators for CVD, pericardial adipose tissue (PAT) and coronary artery calcification (CAC) volume, are lacking. Our study aims to investigate the longitudinal associations of the AHEI score with measures of CAC and PAT in adults with and without type 1 diabetes (T1D)., Methods and Results: The prospective Coronary Artery Calcification in T1D (CACTI) study included 652 people with T1D and 764 people without diabetes (non-DM) (19-56 years old) and was conducted in 2000-2002, 2003-2004, and 2006-2007. At each visit, food frequency questionnaires were collected and PAT and CAC were measured using electron beam computed tomography. Two variables were used for CAC analyses: a continuous variable for the square-root tranformed volume (SRV) for each visit and a second variable identified CAC progression from baseline to visit 3. Mixed effect models and a logistic regression model were used to conduct statistical analyses. A one-point increase in the AHEI score was significantly associated with a -0.12 cm 3 (95% CI: -0.17, -0.08; p-value<0.0001) decrease in PAT volume in combined analyses, a -0.16 cm 3 (95% CI: -0.22, -0.09; p-value<0.0001) decrease in the non-DM group, a marginally significant -0.07 cm 3 (95% CI: -0.14, 0.002; p-value = 0.0571) decrease in the T1D group, and was not associated with either CAC outcome., Conclusion: The AHEI score is inversely associated with PAT; the association revealed greater magnitude of PAT reduction in the non-DM group. The AHEI score did not associate with CAC progression., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: We examined the relationship of midlife cardiovascular health (CVH) with late-life robustness among men and women and the impact of survivorship bias on sex differences in robustness.Methods: Prospective analysis of 15 744 participants aged 45-64 (visit 1 median age: 54 years, 55% female, 27% Black) in 1987-1989 from the population-based Atherosclerosis Risk in Communities Study. CVH was operationalized according to the Life's Simple 7 (LS7) metric of health behaviors (smoking, weight, physical activity, diet, cholesterol, blood pressure, and glucose); each behavior was scored as ideal (2 points), intermediate (1 point), or poor (0 points) and summed. Late-life robust/prefrail/frailty was defined at visit 5 (2011-2013). Multinomial regression estimated relative prevalence ratios (RPRs) of late-life robustness/prefrailty/frailty/death across overall midlife LS7 score and components, for the full visit 1 sample. Separate analyses considered visit 5 survivors-only.Results: For each 1-unit greater midlife LS7 score, participants had a 37% higher relative prevalence of being robust versus frail (overall RPR = 1.37 [95% confidence interval {CI}: 1.30-1.44]; women = 1.45 [1.36-1.54]; men = 1.24 [1.13-1.36]). Among the full visit 1 sample, women had a similar 1-level higher robustness category prevalence (RPR = 1.35 [95% CI: 1.32-1.39]) than men (RPR = 1.31 [95% CI: 1.27-1.35]) for every 1-unit higher midlife LS7 score. Among survivors, men were more likely to be robust than women at lower LS7 levels; differences were attenuated and not statistically different at higher midlife LS7 levels.Conclusions: Midlife CVH is positively associated with robustness in late life among men and women. Accounting for mortality in part explains documented sex differences in robustness across all levels of LS7. [ABSTRACT FROM AUTHOR]

Background: Preventive therapy among patients with established atherosclerotic cardiovascular disease (ASCVD) is generally underused. Whether new guideline recommendations and a focus on implementation have improved the use of high-intensity statins is unknown.Objectives: This study sought to evaluate the patterns and predictors of statin use among patients with ASCVD.Methods: In this retrospective cohort study, pharmacy and medical claims data from a commercial health plan were queried for patients with established ASCVD between January 31, 2018, and January 31, 2019. Statin use on an index date of January 31, 2019, was evaluated, as was 12-month adherence and discontinuation. Multivariable logistic regression was used to determine independent associations with statin use of varying intensities.Results: Of the 601,934 patients with established ASCVD, 41.7% were female, and the mean age was 67.5 ± 13.3 years. Overall, 22.5% of the cohort were on a high-intensity statin, 27.6% were on a low- or moderate-intensity statin, and 49.9% were not on any statin. In multivariable analysis, younger patients, female patients, and those with higher Charlson comorbidity score were less likely to be prescribed any statin. Among statin users, female patients, older patients, and those with peripheral artery disease were less likely to be on a high-intensity formulation, whereas a cardiology encounter in the prior year increased the odds. The majority of high-intensity stain users achieved high levels of adherence.Conclusions: Substantial underuse of statins persists in a large, insured, and contemporary cohort of patients with ASCVD from the United States. In particular, concerning gaps in appropriate statin use remain among younger patients, women, and those with noncoronary ASCVD. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the association of physical activity (PA) with atrial fibrillation (AF) incidence in an elderly population.Methods: We studied 5166 participants of the Atherosclerosis Risk in Communities cohort examined in 2011-2013 free of AF. Self-reported PA was evaluated with a validated questionnaire. Weekly minutes of leisure-time moderate to vigorous physical activity (MVPA) were calculated and categorized using the 2018 Physical Activity Guidelines for Americans (no activity [0 min/week], low [> 0- < 150 min/week], adequate [150- < 300 min/week], high [≥ 300 min/week]). Incident AF through 2019 was ascertained from hospital discharges and death certificates. Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for AF by levels of physical activity adjusting for potential confounders.Results: The mean (SD) age for the sample was 75 (5) years (59% female, 22% Black). During a mean (SD) follow-up time of 6.3 (2.0) years, 703 AF events were identified. The association of MVPA with AF incidence showed a U-shaped relationship. Compared to those not engaging in MVPA, individuals with low MVPA had a 23% lower hazard of AF (HR = 0.77; 95% CI 0.61, 0.96), while those with adequate MVPA had a 14% lower hazard (HR 0.86; 95% CI 0.69, 1.06). High levels of MVPA were not associated with AF risk (HR 0.97; 95% CI 0.78, 1.20).Conclusion: This study suggests that being involved in low to moderate levels of MVPA is associated with lower AF risk, with no evidence of increased risk of AF in those with higher levels of MVPA. [ABSTRACT FROM AUTHOR]

Objective: To assess lifetime cardiovascular disease (CVD) risk by coronary artery calcium (CAC) score in individuals with diabetes from the Multi-Ethnic Study of Atherosclerosis (MESA) and compare risk with that in individuals without diabetes.Research Design and Methods: We developed a microsimulation model with well, diabetes, post-CVD, and death health states using multivariable time-dependent Cox regression with age as time scale. We initially used 10-year follow-up data of 6,769 MESA participants, including coronary heart disease (CHD) (n = 272), heart failure (n = 201), stroke (n = 186), and competing death (n = 619) and assessed predictive validity at 15 years. We externally validated the model in matched National Health and Nutrition Examination Survey (NHANES) participants. Subsequently, we predicted CVD risk until age 100 years by diabetes, 10-year pooled cohort equations risk, and CAC score category (0, 1-100, or 100+).Results: The model showed good calibration and discriminative performance at 15 years, with discrimination indices 0.71-0.78 across outcomes. In the NHANES cohort, predicted 15-year mortality risk corresponded well with Kaplan-Meier risk, especially for those with diabetes: 29.6% (95% CI 24.9-34.8) vs. 32.4% (95% CI 27.2-37.2), respectively. Diabetes increased lifetime CVD risk, similar to shifting one CAC category upward (from 0 to 1-100 or from 1-100 to 100+). Patients with diabetes and CAC score of 0 had a lifetime CVD risk that overlapped with that of individuals without diabetes who were at low 10-year pooled cohort equations risk (<7.5%).Conclusions: Patients with diabetes carry a spectrum of CVD risk. CAC scoring may improve decisions for preventive interventions for patients with diabetes by better delineating lifetime CVD risk. [ABSTRACT FROM AUTHOR]

Background: Understanding the effect of lifestyle and genetic risk on the lifetime risk of coronary heart disease (CHD) is important to improving public health initiatives. Our objective was to quantify remaining lifetime risk and years free of CHD according to polygenic risk and the American Heart Association's Life's Simple 7 (LS7) guidelines in a population-based cohort study.Methods: Our analysis included data from participants of the ARIC (Atherosclerosis Risk in Communities) study: 8372 White and 2314 Black participants; 45 years of age and older; and free of CHD at baseline examination. A polygenic risk score (PRS) comprised more than 6 million genetic variants was categorized into low (<20th percentile), intermediate, and high (>80th percentile). An overall LS7 score was calculated at baseline and categorized into "poor," "intermediate," and "ideal" cardiovascular health. Lifetime risk and CHD-free years were computed according to polygenic risk and LS7 categories.Results: The overall remaining lifetime risk was 27%, ranging from 16.6% in individuals with an ideal LS7 score to 43.1% for individuals with a poor LS7 score. The association of PRS with lifetime risk differed according to ancestry. In White participants, remaining lifetime risk ranged from 19.8% to 39.3% according to increasing PRS categories. Individuals with a high PRS and poor LS7 had a remaining lifetime risk of 67.1% and 15.9 fewer CHD-free years than did those with intermediate polygenic risk and LS7 scores. In the high-PRS group, ideal LS7 was associated with 20.2 more CHD-free years compared with poor LS7. In Black participants, remaining lifetime risk ranged from 19.1% to 28.6% according to increasing PRS category. Similar lifetime risk estimates were observed for individuals of poor LS7 regardless of PRS category. In the high-PRS group, an ideal LS7 score was associated with only 4.5 more CHD-free years compared with a poor LS7 score.Conclusions: Ideal adherence to LS7 recommendations was associated with lower lifetime risk of CHD for all individuals, especially in those with high genetic susceptibility. In Black participants, adherence to LS7 guidelines contributed to lifetime risk of CHD more so than current PRSs. Improved PRSs are needed to properly evaluate genetic susceptibility for CHD in diverse populations. [ABSTRACT FROM AUTHOR]

Purpose: While tree nut consumption has been shown to be cardioprotective, a few studies have examined the relationship between tree nut consumption and carotid atherosclerosis. We tested the hypothesis that tree nut consumption would be inversely related with carotid atherosclerosis in adults. Methods: We cross-sectionally analyzed data from 4536 participants of the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study conducted in the United States. Dietary patterns among participants were variable, tree nut consumption was self-reported using the Food Frequency Questionnaire (FFQ), and B-mode ultrasound of the carotid arteries was used to assess for the presence of carotid artery plaques (primary outcome) and carotid intima media thickness (cIMT). Multivariable logistic regression was used to estimate odds ratio (95% confidence interval) of prevalent carotid artery plaques and linear regression was used to estimate adjusted mean cIMT across categories of nut consumption. Results: The mean age was 52.3 years (SD = 13.6), 95.6% of the participants were white, and 54% were female. The median tree nut intake was 1–3 servings/month. Odds ratios (95% CI) for prevalent carotid artery plaques were 1.0 (reference), 1.03 [0.86, 1.4], 0.89 [0.70, 1.13], and 0.96 [0.73, 1.26] for tree nut consumption of almost never, 1–3 times/month, 1/week, and 2+/week, respectively, adjusting for age, sex, race, field center, BMI, smoking status, alcohol consumption, creatinine, energy intake, fruit and vegetable consumption, exercise, and education. In secondary analysis, there was a suggestive inverse association of tree nut consumption with cIMT in the internal carotid artery, but not the common carotid or bifurcation. Conclusion: Our data showed no association between tree nut consumption and prevalence of carotid artery plaques in adults. [ABSTRACT FROM AUTHOR]

Fructosamine is a measure of short-term glycemic control, which has been suggested as a useful complement to glycated hemoglobin (HbA1c) for the diagnosis and monitoring of diabetes. To date, a single genome-wide association study (GWAS) including 8,951 U.S. White and 2,712 U.S. Black individuals without a diabetes diagnosis has been published. Results in Whites and Blacks yielded different association loci, near RCN3 and CNTN5, respectively. In this study, we performed a GWAS on 20,731 European-ancestry blood donors and meta-analyzed our results with previous data from U.S. White participants from the Atherosclerosis Risk in Communities (ARIC) study (Nmeta = 29,685). We identified a novel association near GCK (rs3757840, βmeta = 0.0062; minor allele frequency [MAF] = 0.49; Pmeta = 3.66 × 10-8) and confirmed the association near RCN3 (rs113886122, βmeta = 0.0134; MAF = 0.17; Pmeta = 5.71 × 10-18). Colocalization analysis with whole-blood expression quantitative trait loci data suggested FCGRT as the effector transcript at the RCN3 locus. We further showed that fructosamine has low heritability (h2 = 7.7%), has no significant genetic correlation with HbA1c and other glycemic traits in individuals without a diabetes diagnosis (P > 0.05), but has evidence of shared genetic etiology with some anthropometric traits (Bonferroni-corrected P < 0.0012). Our results broaden knowledge of the genetic architecture of fructosamine and prioritize FCGRT for downstream functional studies at the established RCN3 locus. [ABSTRACT FROM AUTHOR]

Background: Whereas several interventions can effectively lower lipid levels in people at risk for atherosclerotic cardiovascular disease (ASCVD), cardiovascular event risks remain, suggesting an unmet medical need to identify factors contributing to cardiovascular event risk. Monocytes and macrophages play central roles in atherosclerosis, but studies have yet to provide a detailed view of macrophage populations involved in increased ASCVD risk.Methods: A novel macrophage foaming analytics tool, AtheroSpectrum, was developed using 2 quantitative indices depicting lipid metabolism and the inflammatory status of macrophages. A machine learning algorithm was developed to analyze gene expression patterns in the peripheral monocyte transcriptome of MESA participants (Multi-Ethnic Study of Atherosclerosis; set 1; n=911). A list of 30 genes was generated and integrated with traditional risk factors to create an ASCVD risk prediction model (30-gene cardiovascular disease risk score [CR-30]), which was subsequently validated in the remaining MESA participants (set 2; n=228); performance of CR-30 was also tested in 2 independent human atherosclerotic tissue transcriptome data sets (GTEx [Genotype-Tissue Expression] and GSE43292).Results: Using single-cell transcriptomic profiles (GSE97310, GSE116240, GSE97941, and FR-FCM-Z23S), AtheroSpectrum detected 2 distinct programs in plaque macrophages-homeostatic foaming and inflammatory pathogenic foaming-the latter of which was positively associated with severity of atherosclerosis in multiple studies. A pool of 2209 pathogenic foaming genes was extracted and screened to select a subset of 30 genes correlated with cardiovascular event in MESA set 1. A cardiovascular disease risk score model (CR-30) was then developed by incorporating this gene set with traditional variables sensitive to cardiovascular event in MESA set 1 after cross-validation generalizability analysis. The performance of CR-30 was then tested in MESA set 2 (P=2.60×10-4; area under the receiver operating characteristic curve, 0.742) and 2 independent data sets (GTEx: P=7.32×10-17; area under the receiver operating characteristic curve, 0.664; GSE43292: P=7.04×10-2; area under the receiver operating characteristic curve, 0.633). Model sensitivity tests confirmed the contribution of the 30-gene panel to the prediction model (likelihood ratio test; df=31, P=0.03).Conclusions: Our novel computational program (AtheroSpectrum) identified a specific gene expression profile associated with inflammatory macrophage foam cells. A subset of 30 genes expressed in circulating monocytes jointly contributed to prediction of symptomatic atherosclerotic vascular disease. Incorporating a pathogenic foaming gene set with known risk factors can significantly strengthen the power to predict ASCVD risk. Our programs may facilitate both mechanistic investigations and development of therapeutic and prognostic strategies for ASCVD risk. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. A major risk factor for this condition is increased serum low-density lipoprotein cholesterol (LDL-C) levels for which statins have been successful in reducing serum LDL-C to healthy concentrations. However, patients who are statin intolerant or those who do not achieve their treatment goals while on high-intensity statin therapy, such as those with familial hypercholesterolemia, remain at risk. With the discovery of PCSK9 inhibitors, the ability to provide more aggressive treatment for patients with homozygous and heterozygous familial hypercholesterolemia has increased. Ezetimibe reduces LDL-C by 15%-20% when combined with statin. 2 , 3 Protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been found to achieve profound reductions in LDL-C (54%-74%) when added to statins. They have shown dramatic effects at lowering major adverse cardiovascular events (MACE) in high-risk patients 4 with LDL-C levels ≥70 mg/dL and can be used in populations that are statin intolerant or not at goal levels with maximally tolerated statin therapy. PCSK9 inhibitors also produce minimal side effects. Myopathy, a common side effect for patients on statins, has been rare in patients on PCSK9 inhibitors. Randomized trials have shown that reduction in LDL-C has translated to clinical benefits even in patients who have not achieved their LDL-C target. [ABSTRACT FROM AUTHOR]

Vascular disease is a leading cause of morbidity and mortality in the United States and globally. Pathological vascular remodeling, such as atherosclerosis and stenosis, largely develop at arterial sites of curvature, branching, and bifurcation, where disturbed blood flow activates vascular endothelium. Current pharmacological treatments of vascular complications principally target systemic risk factors. Improvements are needed. We previously devised a targeted polyelectrolyte complex micelle to deliver therapeutic nucleotides to inflamed endothelium in vitro by displaying the peptide VHPKQHR targeting vascular cell adhesion molecule 1 (VCAM1) on the periphery of the micelle. This paper explores whether this targeted nanomedicine strategy effectively treats vascular complications in vivo. Disturbed flow-induced microRNA-92a (miR-92a) has been linked to endothelial dysfunction. We have engineered a transgenic line (miR-92aEC-TG/Apoe-/-) establishing that selective miR-92a overexpression in adult vascular endothelium causally promotes atherosclerosis in Apoe-/- mice. We tested the therapeutic effectiveness of the VCAM-1–targeting polyelectrolyte complex micelles to deliver miR-92a inhibitors and treat pathological vascular remodeling in vivo. VCAM-1–targeting micelles preferentially delivered miRNA inhibitors to inflamed endothelial cells in vitro and in vivo. The therapeutic effectiveness of anti–miR-92a therapy in treating atherosclerosis and stenosis in Apoe-/- mice is markedly enhanced by the VCAM-1–targeting polyelectrolyte complex micelles. These results demonstrate a proof of concept to devise polyelectrolyte complex micelle-based targeted nanomedicine approaches treating vascular complications in vivo [ABSTRACT FROM AUTHOR]

Introduction: Childhood declines in cardiovascular health have been linked to the development of subclinical atherosclerosis; however, less is known about the timing and sequence of the decline of the specific cardiovascular health components. The study objective is to identify the patterns of decline and associations with adulthood subclinical atherosclerosis.Methods: Data were pooled from 5 cardiovascular cohorts. Clinical components of cardiovascular health (BMI, blood pressure, cholesterol, and blood glucose) were categorized as ideal or nonideal using American Heart Association definitions. Multitrajectory models simultaneously fitted the probability ideal for each factor. Adjusted associations between trajectory groups and carotid intima-media thickness were modeled. Data were pooled from December 1, 2015 to June 1, 2019; statistical analysis occurred between June 1, 2019 and June 1, 2020.Results: This study included 9,388 individuals (55% female, 66% White). A total of 5 distinct trajectory groups were created: 1 maintained the ideal levels of all the 4 health factors, 2 had risk onset of a single factor in childhood, 1 had risk onset of multiple factors in childhood, and 1 had risk onset in adulthood. Those with childhood multiple risk onset had 8.1% higher carotid intima-media thickness (95% CI=0.067, 0.095) than those in the ideal group, childhood cholesterol risk onset had 5.9% higher carotid intima-media thickness (95% CI=0.045, 0.072), childhood BMI risk onset had 5.5% higher carotid intima-media thickness (95% CI=0.041, 0.069), and early adulthood multiple risk onset had 2.7% higher carotid intima-media thickness (95% CI=0.013, 0.041).Conclusions: Those who lost the ideal status of cardiovascular health in childhood and early adulthood had more subclinical atherosclerosis than those who retained the ideal cardiovascular health across the life course, underscoring the importance of preserving the ideal cardiovascular health beginning in childhood and continued into adulthood. [ABSTRACT FROM AUTHOR]

This study compared the prognostic value of quantified thoracic artery calcium (TAC) including aortic arch on chest CT and coronary artery calcium (CAC) score on ECG-gated cardiac CT., Methods: A total of 2412 participants who underwent both chest CT and ECG-gated cardiac CT at the same period were included in the Multi-Ethnic Study of Atherosclerosis Exam 5. All participants were monitored for incident atherosclerotic cardiovascular disease (ASCVD) events. TAC is defined as calcification in the ascending aorta, aortic arch and descending aorta on chest CT. The quantification of TAC was measured using the Agatston method. Time-dependent receiver-operating characteristic (ROC) curves were used to compare the prognostic value of TAC and CAC scores., Results: Participants were 69±9 years of age and 47% were male. The Spearman correlation between TAC and CAC scores was 0.46 (p<0.001). During the median follow-up period of 8.8 years, 234 participants (9.7%) experienced ASCVD events. In multivariable Cox regression analysis, TAC score was independently associated with increased risk of ASCVD events (HR 1.31, 95% CI 1.09 to 1.58) as well as CAC score (HR 1.82, 95% CI 1.53 to 2.17). However, the area under the time-dependent ROC curve for CAC score was greater than that for TAC score in all participants (0.698 and 0.641, p=0.031). This was particularly pronounced in participants with borderline/intermediate and high 10-year ASCVD risk scores., Conclusion: Our study demonstrated a significant association between TAC and CAC scores but a superior prognostic value of CAC score for ASCVD events. These findings suggest TAC on chest CT provides supplementary data to estimate ASCVD risk but does not replace CAC on ECG-gated cardiac CT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia)., Methods: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate., Structure: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed., (Copyright © 2024 American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to evaluate the performance of a modified U.S. (MUS) model for risk prediction of cardiovascular (CV) events in Asian patients and compare it to European and Japanese models., Methods: The MUS model, based on the US ACC/AHA 2018 lipid treatment guideline, was employed to stratify patients under primary or secondary prevention. Two multi-center prospective observational registry cohorts, T-SPARCLE and T-PPARCLE, were used to validate the scoring system, and the primary outcome was the time to first occurrence/recurrence of major adverse cardiac events (MACEs). The MUS model's performance was compared to other models from Europe and Japan., Results: A total of 10,733 patients with the mean age of 64.2 (SD: 11.9) and 36.5% female were followed up for a median of 5.4 years. The MUS model was validated, with an AUC score of 0.73 (95% CI 0.68-0.78). The European and Japanese models had AUC scores ranging from 0.6 to 0.7. The MUS model categorized patients into four distinct CV risk groups, with hazard ratios (HRs) as follows: very high- vs. high-risk group (HR = 1.91, 95% CI 1.53-2.39), high- vs. moderate-risk group (HR = 2.08, 95% CI 1.60-2.69), and moderate- vs. low-risk group (HR = 3.14, 95% CI 1.63-6.03). After adjusting for the MUS model, a history of atherosclerotic vascular disease (ASCVD) was not a significant predictor of adverse cardiovascular outcomes within each risk group., Conclusion: The MUS model is an effective tool for risk stratification in Asian patients with and without ASCVD, accurately predicting MACEs and performing comparably or better than other established risk models. Our findings suggest that patient management should focus on background risk factors instead of solely on primary or secondary prevention., Competing Interests: Conflicts of interest The authors declared no conflicts of interest., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background and Aims: Matrix Gla protein (MGP) is an inhibitor of calcification that requires carboxylation by vitamin K for activity. The inactive form of MGP, dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP), has been associated with increased calcification. However, it is not known whether there is a longitudinal relationship between dephosphorylated-uncarboxylated matrix Gla protein levels and coronary and aortic calcification in large population cohorts., Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) followed participants with serial cardiac computed tomography (CT) measures of vascular calcification. Dp-ucMGP was measured at baseline in a subset of participants who completed baseline and follow-up CTs approximately 10 years later and had available plasma specimens (n = 2663). Linear mixed effects models (LMMs) were used to determine the association of dp-ucMGP with the simultaneous incidence and progression of coronary artery, ascending thoracic aortic, or descending thoracic aortic calcification (CAC, ATAC, DTAC)]., Results: For every one standard deviation (SD, 178 pmol/L) increment in dp-ucMGP, CAC increased by 3.44 ([95% CI = 1.68, 5.21], p < 0.001) Agatston units/year (AU/year), ATAC increased by 0.63 ([95% CI = 0.27, 0.98], p = 0.001) AU/year, and DTAC increased by 8.61 ([95% CI = 4.55, 12.67], p < 0.001) AU/year. The association was stronger for DTAC in those ≥65 years and with diabetes., Conclusions: We found a positive association of the inactive form of matrix Gla protein, dp-ucMGP, and long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate dp-ucMGP as a calcification regulator and MGP as a possible therapeutic target to slow progression of calcification in the vasculature., Competing Interests: Declaration of competing interest AEB was the site principal investigator for a sponsored clinical trial by CSL-Behring, Inc. For which her institution received compensation, acknowledges modest honorarium from ClearView Healthcare, LLC, modest honorarium and an unrestricted educational grant to her institution from Zoll, Inc., all outside the published work. JRK reports stock ownership in AbbVie, Abbott, Bristol Myers Squibb, Johnson & Johnson, Medtronic, Merck, and Pfizer., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Racial and ethnic disparities in periodontal disease exist in the United States. This study examined the prevalence of self-reported periodontal disease, and the extent to which racial/ethnic disparities in the reported disease were reduced or eliminated after controlling for various risk factors in a multi-ethnic study population of older adults.Materials and Methods: Information from the baseline examination (July 2000-August 2002) of the Multi-Ethnic Study of Atherosclerosis (MESA) was used. Study participants (N = 6256) were age 45-84 years and identified themselves as either: white, black, Hispanic or Chinese. Periodontal disease was assessed by self-report; demographic and socioeconomic status (SES) indicators, biomedical risk factors and psychosocial stress factors were used as predictors of self-reported periodontal disease.Results: Chinese displayed the highest prevalence of self-reported periodontal disease (39.8%), followed by blacks (32.0%) and whites (26.0%), with Hispanics displaying the lowest prevalence (17.4%). Chinese and black participants had a significantly higher prevalence of disease compared to whites that persisted after adjusting for demographic and SES indicators, biomedical risk factors and psychosocial stress factors. After such adjustment, Hispanics did not differ significantly from whites in their reporting of disease.Conclusion: Racial/ethnic disparities in self-reported periodontal disease persisted after adjusting for all study covariates. This study highlights the need for continued research into the determinants of racial/ethnic disparities in periodontal disease in order to better target interventions aimed at reducing the burden of disease in all segments of the U.S. population. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Cystatin C-based estimated glomerular filtration rate (eGFR cys ) has stronger associations with adverse clinical outcomes than creatinine-based eGFR (eGFR cr ). Obesity may be associated with higher cystatin C levels, independent of kidney function, but it is unknown whether obesity modifies associations of eGFR cys with kidney and cardiovascular outcomes., Study Design: Cohort study., Setting & Participants: 27,249 US adults in the Reasons for Geographic and Racial Differences in Stroke Study., Predictors: eGFR cys , eGFR cr , waist circumference, and body mass index (BMI)., Outcome: All-cause mortality, kidney failure, incident atherosclerotic cardiovascular disease (ASCVD), and incident heart failure (HF)., Analytical Approach: Multivariable Cox and Fine-Gray models with multiplicative interaction terms were constructed to investigate whether waist circumference quartiles or BMI categories modified associations of eGFR cys with risks of 4 clinical outcomes., Results: Participants had a mean age of 65 years; 54% were women, 41% were Black, and 21% had an eGFR cys <60mL/min/1.73m 2 . The baseline prevalence of abdominal obesity (waist circumference≥88cm for women or≥102cm for men) was 48% and obesity was 38%. In multivariable adjusted analyses, each 15mL/min/1.73m 2 lower eGFR cys was associated with higher HR and 95% CI of mortality in each waist circumference quartile (first quartile, 1.19 [1.15-1.24]; second quartile, 1.22 [1.18-1.26]; third quartile, 1.20 [1.16-1.24]; fourth quartile, 1.19 [1.15-1.23]) as well as within each BMI category (BMI<24.9: 1.21 [1.17-1.25]; BMI 25.0-29.9: 1.21 [1.18-1.25]; BMI 30.0-34.9: 1.20 [1.16-1.25]; BMI≥35: 1.17, [1.12-1.22]). Neither waist circumference nor BMI modified the association of eGFR cys with mortality, kidney failure, incident ASCVD, or incident HF (all P interaction >0.05)., Limitations: Included only Black and White persons in the United States., Conclusion: Obesity did not modify the association of eGFR cys with all-cause mortality, kidney failure, incident ASCVD, or incident HF. Among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes., Plain-Language Summary: Cystatin C is increasingly used in clinical practice to estimate kidney function, and cystatin C-based eGFR (eGFR cys ) may be used to determine risk for adverse clinical outcomes. Adiposity may increase serum levels of cystatin C, independent of kidney function. This cohort study investigated whether associations of eGFR cys with adverse kidney and cardiovascular outcomes are modified by measures of obesity, waist circumference, and body mass index. We found that obesity does not modify associations of eGFR cys with 4 clinical outcomes and conclude that among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes., (Published by Elsevier Inc.)

Importance: Reducing exposure to fine particulate matter (<2.5 μm [PM2.5]) air pollution improves cardiopulmonary morbidity and mortality. However, the public health relevance of air quality index (AQI) activity guidelines under present-day environmental conditions in the US has not been critically assessed., Objective: To evaluate the public health relevance of following PM2.5 AQI activity guidance in preventing serious atherosclerotic cardiovascular disease (ASCVD) and pulmonary events among adults in the US., Design, Setting, and Participants: This cross-sectional modeling study involved the general adult population and sensitive individuals as designated by the US Environmental Protection Agency (EPA), including adults with preexisting ASCVD or lung disease (asthma or chronic obstructive pulmonary disease). The study was conducted between August 1, 2023, and January 31, 2024., Exposures: Daily AQI strata for PM2.5 and the corresponding activity recommendations., Main Outcomes and Measures: The main outcome was the number needed to treat (NNT) per day by following activity guidance across daily AQI strata to prevent 1 serious ASCVD or pulmonary event among relevant populations. To calculate PM2.5-induced excess disease event rates per day, estimated baseline disease-specific daily event rates for each group were multiplied by the increase in risks due to PM2.5 levels at each AQI stratum. The number of events prevented per day was calculated by multiplying each excess disease event rate by the percentage in exposure reduction plausibly incurred by following population-specific activity guidance at each AQI level. The NNT is the reciprocal of the number of events prevented., Results: The NNT to prevent ASCVD events was high for the general population and for patients with ASCVD across all AQI strata. The range of values was comparatively lower to prevent pulmonary events among adults with lung disease. During most days (96%) when activity recommendations were promulgated due to elevated PM2.5 (AQI, 101-200), the NNT to prevent a serious disease event remained very high for the general population (>18 million), patients with ASCVD (approximately 1.6-5 million), and adults with lung disease (approximately 66 000-202 000)., Conclusions and Relevance: These findings suggest that existing PM2.5 AQI activity recommendations are of questionable public health relevance in present-day conditions and merit consideration for updating to improve their potential effectiveness.

Disruption of vulnerable atherosclerotic plaques often leads to myocardial infarction and stroke, the leading causes of morbidity and mortality in the United States. A diagnostic method that detects early‐stage high‐risk atherosclerotic plaques could prevent these sequelae. The abundant immune cells in the arterial wall, especially inflammatory Ly‐6Chi monocytes and foamy macrophages, are indicative of plaque inflammation, and may be associated with plaque vulnerability. Hence, a new method is sought to develop that specifically targets these immune cells to offer clinically relevant diagnostic information about cardiovascular disease. Ultraselective nanoparticle targeting of Ly‐6Chi monocytes and foamy macrophages and clinically‐viable photoacoustic imaging (PAI) are combined in order to precisely and specifically image inflamed plaques ex vivo in a mouse model that mimics human vulnerable plaques histopathologically. Within the plaques, high‐dimensional single‐cell flow cytometry (13‐parameter) shows that the nanoparticles are almost‐exclusively taken up by the Ly‐6Chi monocytes and foamy macrophages that heavily infiltrate plaques. PAI identifies inflamed atherosclerotic plaques that display ≈6‐fold greater signal compared to controls (P < 0.001) 6 h after intravenous injection of ultraselective carbon nanotubes, with in vivo corroboration via optical imaging. This highly‐selective strategy may provide a targeted, noninvasive imaging strategy to accurately identify and diagnose inflamed atherosclerotic lesions. [ABSTRACT FROM AUTHOR]

Background: Despite using identical evidence to support practice guidelines for lipid-lowering treatment in primary prevention of cardiovascular disease (CVD), it is unclear to what extent the 2018 American Heart Association/American College of Cardiology/Multisociety, 2016 US Preventive Services Task Force (USPSTF), 2020 Department of Veterans Affairs/Department of Defense, 2021 Canadian Cardiovascular Society, and 2019 European Society of Cardiology/European Atherosclerosis Society guidelines differ in grading and assigning levels of evidence and classes of recommendations (LOE/class) at a population level.Methods: We included 7262 participants, aged 45 to 75 years, without history of CVD from the prospective population-based Rotterdam Study. Per guideline, proportions of the population recommended statin therapy by LOE/class, sensitivity and specificity for CVD events, and numbers needed to treat at 10 years were calculated.Results: Mean age was 61.1 (SD 6.9) years; 58.2% were women. American Heart Association/American College of Cardiology/Multisociety, USPSTF, Department of Veterans Affairs/Department of Defense, Canadian Cardiovascular Society, and European Society of Cardiology/European Atherosclerosis Society strongly recommended statin initiation in respective 59.4%, 40.2%, 45.2%, 73.7%, and 42.1% of the eligible population based on high-quality evidence. Sensitivity for CVD events for treatment recommendations supported with strong LOE/class was 86.3% for American Heart Association/American College of Cardiology/Multisociety (IA or IB), 69.4% for USPSTF (USPSTF-B), 74.5% for Department of Veterans Affairs/Department of Defense (strong for), 93.3% for Canadian Cardiovascular Society (strong), and 66.6% for European Society of Cardiology/European Atherosclerosis Society (IA). Specificity was highest for the USPSTF at 45.3% and lowest for European Society of Cardiology/European Atherosclerosis Society at 10.0%. Estimated numbers needed to treat at 10 years for those with the strongest LOE/class were ranging from 20 to 26 for moderate-intensity and 12 to 16 for high-intensity statins.Conclusions: Sensitivity, specificity, and numbers needed to treat at 10 years for assigned LOE/class varied greatly among 5 CVD prevention guidelines. The level of variability seems to be driven by differences in how the evidence is graded and translated into LOE/class underlying the treatment recommendations by different professional societies. Efforts towards harmonizing evidence grading systems for clinical guidelines in primary prevention of CVD may reduce ambiguity and reinforce updated evidence-based recommendations. [ABSTRACT FROM AUTHOR]

Growing evidence has identified nocturia as a potential manifestation of several cardiovascular disease states. We aimed to determine whether a relationship exists between nocturia and global atherosclerotic cardiovascular disease (ASCVD) risk, defined by the American College of Cardiology/American Heart Association (ACC/AHA) ASCVD risk calculator, using a large nationally-representative study sample from the United States. We explored potential associations between nocturia and ASCVD risk in adults aged 40–79 years with no prior history of overt/known atherosclerotic disease from 7 consecutive cycles of the National Health and Nutrition Examination Survey. Subjects were classified by whether they met the ASCVD high-risk threshold following current ACC/AHA consensus guidelines (10-year major adverse cardiovascular event risk ≥ 20%). Logistic regression analyses were used to explore associations between nocturia (defined as ≥ 2 nocturnal voids) and ASCVD risk. The prevalence of nocturia and high ASCVD risk were 27.0% and 10.9%, respectively. Nocturia, older age, increased body mass index, and diuretic use were associated with high ASCVD risk on univariate logistic regression. After adjusting for age, body mass index, and diuretic use, nocturia remained associated with significantly greater odds of high ASCVD risk in females but not in males. Elicitation of nocturia on clinical history taking may serve to identify high cardiovascular risk in females. Future studies are needed to elucidate mechanisms underlying this association. [ABSTRACT FROM AUTHOR]

Atherosclerosis, hardening of the arteries, originates from small plaques in the arteries; it is a major cause of disability and premature death in the United States and worldwide. In this paper, we study the bifurcation of a highly nonlinear and highly coupled PDE model describing the growth of an arterial plaque in the early stage of atherosclerosis. The model involves LDL and HDL cholesterols, macrophage cells, and foam cells, with the interface separating the plaque and blood flow regions being a free boundary. We establish finite branches of symmetry-breaking stationary solutions which bifurcate from the radially symmetric solution. Since plaques in reality are unlikely to be strictly radially symmetric, our result would be useful to explain the asymmetric shapes of plaques. [ABSTRACT FROM AUTHOR]

Background: Preliminary evidence suggests associations between neighborhood park access and better late-life cognition and reduced Alzheimer's disease (AD) risk.Objective: Examine associations between neighborhood park access and longitudinal change in cognition among U.S. older adults without dementia.Methods: We used 2000-2018 observational data from the population-based, multi-site Multi-Ethnic Study of Atherosclerosis (n = 1,733). Measures included proportion of neighborhood park space (park access), distance to nearest park, and 6-year dichotomous and continuous change in scores on the Cognitive Abilities Screening Instrument (CASI; global cognition) and Digit Symbol Coding task (processing speed). Multivariable random intercept models tested main associations and mediation by depressive symptoms, physical activity, and PM2.5 exposure. Effect modification by race (African Americans/Blacks versus Whites) was tested using interaction terms.Results: Greater park access (equivalent to 10%more in 1/2-mile around home) was associated with maintained/improved CASI score over six years independent of several covariates including individual- and neighborhood-level socioeconomic status (Odds ratio: 1.04; 95%confidence interval: 1.00-1.08). No other associations were observed with the dichotomous or continuous measures of cognitive change and no mediators were found. While a borderline association was seen between greater park access and maintained/improved CASI for African Americans/Blacks but not for Whites, effect modification was not confirmed by testing interaction terms.Conclusion: Neighborhood park access may help maintain/improve late-life global cognition. However, our findings need replication in other population-based studies and regions. Additionally, studies are needed to determine if associations between park access and change in cognition vary by race/ethnicity to inform intervention efforts. [ABSTRACT FROM AUTHOR]

Background: Poor sleep may contribute to chronic kidney disease (CKD) through several pathways, including hypoxia-induced systemic and intraglomerular pressure, inflammation, oxidative stress and endothelial dysfunction. However, few studies have investigated the association between multiple objectively measured sleep dimensions and CKD.Methods: We investigated the cross-sectional association between sleep dimensions and CKD among 1895 Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study participants who completed in-home polysomnography, wrist actigraphy and a sleep questionnaire. Using Poisson regression models with robust variance, we estimated separate prevalence ratios (PR) and 95% CIs for moderate-to-severe CKD (glomerular filtration rate <60 mL/min/1.73 m2 or albuminuria >30 mg/g) among participants according to multiple sleep dimensions, including very short (≤5 hours) sleep, Apnoea-Hypopnoea Index and sleep apnoea-specific hypoxic burden (SASHB) (total area under the respiratory event-related desaturation curve divided by total sleep duration, %min/hour)). Regression models were adjusted for sociodemographic characteristics, health behaviours and clinical characteristics.Results: Of the 1895 participants, mean age was 68.2±9.1 years, 54% were women, 37% were white, 28% black, 24% Hispanic/Latino and 11% Asian. Several sleep metrics were associated with higher adjusted PR of moderate-to-severe CKD: very short versus recommended sleep duration (PR=1.40, 95% CI 1.06 to 1.83); SASHB (Box-Cox transformed SASHB: PR=1.06, 95% CI 1.02 to 1.12); and for participants in the highest quintile of SASHB plus sleep apnoea: PR=1.28, 95% CI 1.01 to 1.63.Conclusions: Sleep apnoea associated hypoxia and very short sleep, likely representing independent biological mechanisms, were associated with a higher moderate-to-severe CKD prevalence, which highlights the potential role for novel interventions. [ABSTRACT FROM AUTHOR]