Search

Controlling blood pressure (BP) is essential in the management of patients with chronic kidney disease. Reflecting the intrinsic variability of BP, several parameters of BP over time have been shown to predict adverse outcomes. Systolic BP time in target range has been recently proposed as a new promising parameter. Park et al.confirmed its prognostic value in patients with chronic kidney disease. We review the potential clinical usefulness and challenges of this parameter in nephrology care.

The association of periodontal disease with atherosclerotic cardiovascular diseases is well known, but not specifically with incident peripheral artery disease (PAD). Therefore, we studied the associations of periodontal disease with incident PAD in a population‐based setting. Among 9,793 participants (aged 53–75 years) without prevalent PAD, self‐reported history of periodontal disease was ascertained. Of these, 5,872 participants underwent full‐mouth examinations from which periodontal status was defined using the US Centers for Disease Control and Prevention‐American Academy of Periodontology (CDC‐AAP) definition. We quantified the association of periodontal disease with incident PAD (defined by hospital admission diagnosis or procedures) using multivariable Cox regression models. During a median follow‐up of 20.1 years, 360 participants (3.6%) developed PAD. In models accounting for potential confounders including diabetes and smoking pack‐years, there was higher hazard of PAD in participants with self‐reported tooth loss because of periodontal disease (hazard ratio:1.54 [95% CI:1.20–1.98]), history of periodontal disease treatment (1.37 [1.05–1.80]), and periodontal disease diagnosis (1.38 [1.09–1.74]), compared to their respective counterparts. The clinical measure of periodontal disease (n = 5,872) was not significantly associated with incident PAD in the fully adjusted model (e.g., 1.53 [0.94–2.50] in CDC‐AAP‐defined severe periodontal disease versus no disease). We observed a modest association of self‐reported periodontal disease, especially when resulting in tooth loss, with incident PAD in the general population. Nonetheless, a larger study with the clinical measure of periodontal disease is warranted.

Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework.

Aims Systematic reviews report an association between poorer oral health and an increased risk of coronary heart disease. This contentious relationship may not be causal but existing studies have been insufficiently well powered comprehensively to examine the role of confounding, particularly by cigarette smoking. Accordingly, we sought to examine the role of smoking in generating the relationship between oral health and coronary heart disease in life-long non-smokers.Methods and results In the Korean Cancer Prevention Study, 975,685 individuals (349,579 women) aged 30–95 years had an oral examination when tooth loss, a widely used indicator of oral health, was ascertained. Linkage to national mortality and hospital registers over 21 years of follow-up gave rise to 64,784 coronary heart disease events (19,502 in women). In the whole cohort, after statistical adjustment for age, there was a moderate, positive association between tooth loss and coronary heart disease in both men (hazard ratio for seven or more missing teeth vs. none; 95% confidence interval 1.08; 1.02, 1.14; Ptrendacross tooth loss groups <0.0001) and women (1.09; 1.01, 1.18; Ptrend0.0016). Restricting analyses to a subgroup of 464,145 never smokers (25,765 coronary heart disease events), however, resulted in an elimination of this association in men (1.01; 0.85, 1.19); Ptrend0.7506) but not women (1.08; 0.99, 1.18; Ptrend0.0086).Conclusion In men in the present study, the relationship between poor oral health and coronary heart disease risk appeared to be explained by confounding by cigarette smoking so raising questions about a causal link.

Reported associations of estimated glomerular filtration rate (eGFR) with cancer risk are inconsistent, and data for the proteinuria-cancer relationship are sparse. We sought to quantify the associations of cancer incidence with eGFR and with proteinuria in a large population-based cohort.

Some evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease.

Introduction:Femur fracture can have devastating consequences in older patients. Lower extremity peripheral artery disease (PAD) reduces physical function, which can in turn increase the risk of falls. However, less is known regarding the association of PAD with incident femur fracture in older adults.Hypothesis:PAD is associated with a higher risk of incident femur fracture independent of potential confounders.Methods:We included 5,276 participants from ARIC Visit 5 (2011-2013) (mean age 76 [standard deviation: 5] years, 57% women and 22% self-identified Black race). Femur fractures were defined as an outpatient encounter or hospitalization with ICD-9 codes: 820-821 or ICD-10 codes: S72. We quantified the association of PAD status at baseline, based on ankle-brachial index (ABI) ≤0.9 or clinical history of PAD, with incident femur fracture using multivariable Cox regression and follow-up until 2019.Results:There were 224 incident femur fractures over a median follow-up of 7.2 [IQI 5.6-7.8] years. The incidence rate of femur fracture was almost 2-times higher in participants with PAD compared to those without a history of PAD and ABI 1.11-1.20 (reference group) (10.5 [7.5-14.8] vs. 5.5 [4.3-6.9] per 1,000 person-years). This association persisted after accounting for demographic (hazards ratio [HR]: 1.86 [95% CI 1.23-2.84] in Model 1) and other confounders (HR 1.59 [1.04-2.46] in Model 2) (Table). When we excluded participants with a clinical history of PAD, low ABI (≤0.9) remained significantly associated with incident femur fracture compared to the reference group (HR 1.94 [1.18-3.19]). Our findings were consistent in demographic and clinical subgroups (e.g., by sex and diabetes status).Conclusions:In community-dwelling older adults, PAD, even when not clinically diagnosed, was associated with an increased risk of femur fracture. Clinicians and patients should be aware of this complication of PAD and consider preventive measures to avoid falls (e.g., exercise counseling, and making home safer).

Background:Physical activity (PA) fragmentation, an emerging concept of PA patterns, indicates the frequency of transitioning from an active to a sedentary state. Whether PA fragmentation provides prognostic information beyond conventional PA measures is unclear, especially in Hispanics/Latinos.Aim:To examine the association between PA fragmentation and mortality in Hispanics/Latinos.Methods:We included 9,856 participants (mean age 41.7 [SE 0.27] years; 52.1% women) from HCHS/SOL with baseline PA evaluation from an Actical accelerometer (≥3 days with ≥10 hr/day of wear). We defined sedentary as <10 counts/min and active as ≥10 counts/min. PA fragmentation was calculated using the active-to-sedentary transition probability (ASTP), defined as the reciprocal of the average active bout duration on a minute-level basis across valid days. We used daily mean total log activity counts (TLAC) as a measure of total PA volume. We modeled the residuals of ASTP regressed on TLAC (total-PA-adjusted ASTP) to investigate ASTP independently of total PA. Deaths were identified from annual follow-up contacts until December 31, 2018. We explored multivariable Cox regression models accounting for the multi-stage sampling design.Results:There were 242 deaths (2.5%) over a mean of 7.1 years. ASTP was associated with mortality in all models (Table). Each 0.10-unit increase of ASTP at baseline was associated with a 38% higher mortality risk after accounting for demographic, clinical, and lifestyle factors. Similarly, the highest ASTP tertile indicated a 2-times greater risk of death compared to the lowest tertile. The results were largely similar when we modeled using total-PA-adjusted ASTP. Higher TLAC was also associated with reduced mortality. Similar results were observed after excluding early deaths (first 2 years).Conclusion:PA fragmentation was robustly associated with mortality, independent of total PA volume. Our findings support PA fragmentation as an emerging novel measure that is informative beyond total PA.

Background:High dietary calcium and phosphorus intakes may accelerate vascular calcification. A few studies have explored the association of dietary calcium and phosphorus intakes with vascular calcification but reported inconsistent results. Most studies relied on dietary assessment at one time point and evaluated only coronary artery calcification.Aim:To assess the associations of dietary calcium and phosphorus intakes over two time points during middle age with coronary artery and extra-coronary calcification at older age.Methods:We studied 1,940 ARIC participants who underwent chest CT scans at ≥75 years of age in 2018-19 and completed a 66-item food frequency questionnaire at two earlier visits (1987-89 and 1993-95). We calculated the average of dietary calcium and phosphorus intakes across these two visits. Calcification was quantified as Agatston score in coronary arteries, ascending aorta, descending aorta, aortic valve ring, aortic valve, and mitral valve. We ran multivariable linear (for continuous Agatston score) and logistic regression models (for Agatston score >75thpercentile).Results:The mean dietary calcium and phosphorus intake was 659 mg/day and 1,074 mg/day, respectively. Overall, we did not observe any positive associations of dietary calcium intake with vascular/valvular calcification. Rather, we saw its inverse association with ascending aorta calcification (Figure). In contrast, dietary phosphorus was not associated with the calcification of any vascular beds. The results were largely similar in linear regression models and after excluding 332 participants (17%) taking calcium supplements.Conclusion:Dietary calcium intake at middle age was largely neutral in its association with vascular calcification while showing a mild inverse association with ascending aorta calcification at older age. No evident associations were seen for dietary phosphorus. Our findings do not support a concern that a calcium or phosphorus-rich diet may accelerate vascular calcification.

Introduction:Psychosocial factors (social isolation, social support, trait anger, and depressive symptoms) are associated with cardiovascular disease risk factors and incidence; few studies investigate whether they are associated with cardiovascular health (CVH), and none with a new definition of CVH, Life’s Essential 8 (LE8) published by the American Heart Association (AHA).Hypothesis:Cross-sectional associations of psychosocial factors and CVH will be inverse, and will be modified by sex and race.Methods:We included 11,674 ARIC cohort participants (58% women; 23% Black; mean age 57 (standard deviation (SD): 6) years) who attended Visit 2 (1990-1992) and had complete data. All psychosocial factors and the following LE8 components were measured at Visit 2: nicotine exposure, sleep, body mass index, blood lipids, blood glucose, and blood pressure. Physical activity and diet were measured at Visit 1 (1987-1989). Psychosocial factors were categorized per standard convention or by tertiles. LE8 was scored per the AHA definition (0-100 range). Associations of each psychosocial factor with continuous LE8 score were assessed using multivariable linear regressions.Results:Mean LE8 score was 61 (SD: 15). Poorer scores on psychosocial factor assessments were associated with lower LE8 scores, with the largest magnitude of association for depressive symptoms (Figure). Participants with high levels of depressive symptoms had an LE8 score 8 points lower than those with low levels of depressive symptoms. Stratum-specific estimates and p-values for interaction terms suggested no modification by sex; however psychosocial factors were associated with approximately a 1 point lower LE8 score in White participants than in Black participants.Conclusion:Poorer psychosocial health factors were associated with lower CVH among middle-aged men and women in ARIC. Future work could investigate whether psychosocial factors modify the relationship between CVH and incident cardiovascular disease.

Background:Regular physical activity (PA) has been associated with reduced risk of coronary heart disease, but conflicting results have been reported regarding its association with coronary artery calcification (CAC), one of the strongest predictors of cardiovascular disease. Moreover, different domains of PA (e.g., sports vs. work) and extra coronary calcification (ECC) have not been extensively studied in this context.Methods:We investigated 2,025 ARIC participants (age 73-95 years) who had no coronary heart disease and underwent a non-contrast cardiac-gated computed tomography scan at visit 7 (2018-19). PA was based on a modified Baecke questionnaire, which provides total and domain-specific (sport, non-sport leisure, and work) PA scores. We modeled the cumulative PA scores in middle-age at visit 1 (1987-89) and visit 3 (1993-95). We explored continuous CAC and ECC (log-transformed [Agatston score+1]) or any CAC and ECC (Agatston score >0 vs. 0) as dependent variables using linear regression and multivariable logistic models, as appropriate.Results:Higher total and domain-specific PA scores showed no association with lower CAC. Among ECC, descending aorta calcification demonstrated the strongest association with total PA scores (coefficient -0.10 [95% CI -0.21, 0.01], p=0.075) (Figure). When specific domains were explored, higher sport and work PA scores were significantly associated with lower descending aorta calcification. When we analyzed any CAC and ECC as the outcome variable, the results were generally consistent.Conclusions:Higher PA in midlife was associated with lower calcification of descending aorta in late life. Our results further support the health benefits of PA and unique pathological process across different vascular beds.

Background:Inflammation plays an important role in the pathophysiology of atherosclerosis. However, inflammatory biomarkers have been found to have a weak association with coronary artery calcium (CAC), a representative measure of subclinical atherosclerosis. Moreover, the existing evidence does not sufficiently explore extra coronary calcium (ECC) in this context.Aim:To characterize the association of two inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) and galectin-3, with CAC and ECC in a community-based cohort.Methods:Cardiac CT was performed among 1,934 ARIC participants (age 53-74 years) without coronary heart disease at visit 7 (2018-19). We examined the associations of hs-CRP and galectin-3 measured in middle age at visit 4 (1996-98) by quartile with the presence of CAC and ECC (Agatston score >0 vs. 0) using multivariable logistic regression.Results:Higher hs-CRP was associated with calcifications in the ascending aorta, aortic valve ring, mitral valve and right coronary artery in the unadjusted model (Table). These associations were mostly attenuated after adjusting for potential confounders, but the associations with ascending aorta and right coronary artery calcifications remained significant (adjusted odds ratio (aOR) = 1.45 [95% CI = 1.02-2.07]) and (1.55 [1.12-2.16]) for the highest vs. lowest quartiles, respectively). Galectin-3 was also independently associated with right coronary artery calcification after adjusting for potential confounders (aOR 1.48 [1.02 - 2.01]) for the highest vs. lowest quartiles). These associations were generally consistent in demographic subgroups.Conclusions:Both hs-CRP and galectin-3 were associated with calcification of some but not all vascular beds tested, suggesting potentially unique atherosclerotic pathophysiology across different vascular beds. Robust associations of inflammatory markers with right coronary artery calcification deserve further investigation.

Introduction:Cardiovascular disease (CVD) and cancer share risk factors, including smoking and obesity. Indeed, an increased cancer risk was reported among patients with CVD, such as myocardial infarction. Lower extremity peripheral artery disease (PAD) has also been explored in this context, but most previous studies included only Whites, had follow-up <10 years, or did not account for key confounders like smoking.Hypothesis:PAD is independently associated with long-term cancer risk in a bi-racial cohort.Methods:We studied 13,102 ARIC participants without prevalent cancer at visit 1 (1987-89) (mean age 54 [SD 6] years, 54% women, and 26% Black) (funding: NHLBI, NCI, and NPCR). Incident cancer was ascertained by linkage to cancer registries and medical record review. We categorized PAD status at visit 1 into symptomatic PAD (intermittent claudication or a history of lower extremity revascularization), asymptomatic PAD (ankle brachial index [ABI] ≤0.9), and other ABI categories of >0.9-1.0, >1.0-1.1, >1.1-1.2, >1.2-1.3 and >1.3. We ran multivariable Cox models.Results:During the median follow-up of 25 years (IQI 15-27 years), there were 4,142 incident cancer cases. 25-year cumulative cancer incidence was 48% in symptomatic PAD, 39% in asymptomatic PAD, and 31-34% in the other categories. When we adjusted for demographic factors, both symptomatic and asymptomatic PAD showed significant hazard ratios for incident cancer (1.79 [95%CI 1.33-2.43] and 1.39 [1.18-1.63], respectively, vs. ABI 1.1-1.2, Model 1 in Table). After adjusting for additional potential confounders, including smoking and diabetes, these associations were somewhat attenuated but remained consistent (Models 2-4 in Table).Conclusion:Both symptomatic and asymptomatic PAD were associated with an increased risk of cancer independently of smoking and diabetes. Although potential mechanisms should be explored, clinicians should be aware of this excess cancer risk among patients with PAD when considering cancer prevention and screening.

Introduction:The 2021 AHA/ACC Chest Pain Guideline classifies the likelihood of ischemia according to chest symptom characteristics. However, the associations of various chest symptoms with long-term risk of different cardiovascular disease (CVD) have not been fully investigated.Aim:To quantify the associations of chest pain and dyspnea with incident major CVD.Methods:In 13,200 ARIC participants (mean age 54 [SD 6] years, 56% female, 25% Blacks) without prior CVD at visit 1 (1987-89), we categorized chest pain into definite angina, possible angina, non-anginal chest pain, and no chest pain based on the WHO Rose questionnaire, and dyspnea into grade 0, 1, 2, and 3-4 based on the Medical Research Council scale. CVD outcomes included myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), and ischemic stroke (median follow-up, 26-28 years). We estimated 30-year cumulative incidence accounting for competing risk of deaths and ran multivariable Cox models.Results:Definite angina and possible angina were robustly associated with incident MI (Table), with adjusted HR 1.83 (95%CI 1.51-2.22) and 1.64 (1.26-2.13), respectively. These two chest pain types were also related to HF, AF, and ischemic stroke, although possible angina did not reach statistical significance for stroke. Even non-anginal chest pain was associated with MI, HF, and AF. Dyspnea showed graded association with all CVD outcomes, but particularly with MI and HF (bottom half of Table). For example, grade 3-4 and 2 showed HR of 2.13 (1.71-2.65) and 1.41 (1.13-1.76), respectively, for MI. When chest pain and dyspnea were modeled simultaneously, their associations were independent.Conclusions:In persons without prior CVD, chest pain and dyspnea were independently associated with different CVD events over 30 years. Our findings suggest broad prognostic implications of chest pain beyond coronary disease and emphasize the importance of recognizing dyspnea for CVD risk management.

Introduction:Physical activity (PA) is associated with a reduced risk of mortality and cardiovascular disease in the general population. However, it is unclear whether PA level in midlife impacts prognosis after myocardial infarction (MI) in later life.Methods:In 1,115 ARIC participants with incident non-fatal MI during ARIC follow-up (mean age 73 [SD 9] years at MI, 54% men, 21% Black), PA prior to incident MI (premorbid PA) was evaluated at visit 1 (1987-89) and visit 3 (1993-95) using a modified Baecke questionnaire; we studied the cumulative PA index scores across these two visits. Total and domain-specific PA (sport, leisure time, and work PA) were analyzed for their associations with mortality, recurrent MI, stroke, and heart failure after MI using multivariable Cox models. Elapsed time between visit 3 and incident MI was on average 11.9 (SD 6.9) years.Results:During a median follow-up of 2.0 [IQI 0.03-8.0] years after incident MI, 914 participants (82%) developed a composite outcome. The 8-year cumulative incidence of composite outcome was lower in the highest tertile of premorbid total PA than the lowest tertile (62% vs. 72%, respectively) (Figure). When adjusting for MI risk factors, the association was not significant. However, for individual outcomes, higher premorbid total PA was associated with a lower risk of recurrent MI (adjusted hazard ratio [HR] 0.66 [95% CI 0.45, 0.96] for the highest vs. lowest tertile). Results were similar for sport and work PA but not leisure time PA. When we focused on short-term prognosis within one year after MI, both higher total PA and sport PA were associated with lower mortality (HR 0.62 [95% CI 0.43, 0.90] and 0.62 [0.44, 0.89], respectively).Conclusions:Greater premorbid PA was associated with better prognosis after MI occurrence, both short-term and long-term post-MI. Our results demonstrate additional prognostic advantage of PA beyond reducing the risk of incident MI.

Supplemental Digital Content is available in the text.

Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white).

Background To describe the rationale, objectives, protocol, and preliminary results for a new prospective cohort study of cardiovascular disease (CVD) risk factors in South Korea.Methods Study members were recruited from participants in routine health assessments at health promotion centres across South Korea. Established and emerging CVD risk factors were measured. Eighteen centres holding electronic health records agreed to linkage of participants’ records to future health insurance claims for monitoring of disease events. The recruitment of 430,920 participants (266,782 men, 164,138 women), aged 30–74 years, provides broad geographical reach across South Korea.Results Risk factor prevalence was more favourable in women than men, and, in general, in the younger rather than older study members. There was also close similarity between the characteristics of the present sample and the Korean National Health and Nutrition Examination Survey. The expected associations between risk factors and both CVD and death were also apparent.Conclusions Data from the present sample, based on data linkage, show close agreement with South Korea-wide surveys (for risk factor prevalence) and the extant literature (for risk factor associations). These findings gives confidence in future results anticipated from this cohort study of east Asians – a group that has been traditionally under-researched.

To quantify the association of peripheral artery disease (PAD) with infection risk because PAD has been understudied despite recognition of atherosclerotic cardiovascular disease as a risk factor for infection.

Introduction:Despite robust evidence of its effectiveness for secondary prevention, cardiac rehabilitation (CR) is underutilized. Understanding individual-level predictors of CR use can guide interventions to boost CR participation.Hypothesis:Clinical, psychosocial and socioeconomic predictors impact CR participation.Methods:We studied 1,255 participants from the ARIC Study with cardiovascular disease (CVD) events eligible for CR (myocardial infarction, coronary revascularization, valve surgery) from data linked to Medicare claims (1991-2015). Predictors including comorbidities, functional status, cognitive function, social support, social network, educational attainment, and household income were ascertained from study visits and annual follow-up at the time point closest to the index CVD event. CR participation was defined as having Current Procedural Terminology codes 93797 and 93798. We examined multiple predictors using logistic regression with the Modified Allen-Cady stepwise backward selection of covariates in addition to age, race, sex, and ARIC center.Results:The mean age was 72.4 (SD 5.2) years (16% Black, 43% women) and 26% participated in CR. In multivariate analyses, variables associated with lower CR participation were income <$12,000 (odds ratio (OR) 0.46 [95% CI 0.24 - 0.89]) vs. >$50,000; < high school education (OR 0.48 [0.27 - 0.86]) vs. graduate/professional education; lowest quartile of cognitive function (OR 0.52 [0.32 - 0.85]) vs. the highest quartile; lowest quartile of social support (OR 0.65 [0.44 - 0.96]) vs. the highest quartile; and current smoking (OR 0.55 [0.31 - 0.96]). Comorbidities and social network were not associated with CR participation.Conclusions:Cognitive function, social support, and SES were robustly associated with CR participation. Efforts to address the gap in CR participation should focus on interventions that support patients with low cognitive function, social supports, and SES.

Background:Kidney function is a crucial determinant of bone-mineral metabolism (BMM); however, the contribution of kidney dysfunction, especially at mild to moderate stages, to vascular calcification remains controversial. Moreover, little is known about whether BMM markers are associated with coronary artery calcification (CAC) and extra-coronary calcification (ECC) beyond kidney function.Methods:In 1935 ARIC participants (age 73-95 years) with no coronary heart disease and data on CAC and ECC at visit 7 (2018-2019), we evaluated estimated glomerular filtration (eGFR) (based on creatinine, cystatin C, and both) and serum BMM markers (calcium, fibroblast growth factor 23, magnesium, parathyroid hormone, and phosphorus) as exposures. The exposures were modeled as weighted averages over ~15 years (visit 1 [1987-89] to visit 5 [2011-13] to allow a lag time for vascular calcification), and the outcome variables were high CAC and ECC (sex-race specific ≥75thvs. <75thpercentile Agatston score) or any CAC and ECC (Agatston score >0 vs. 0) using multivariable logistic regression.Results:Low eGFR (overall range 30-149 mL/min/1.73m2), regardless of equations, was not robustly associated with high CAC and ECC. Among BMM markers, only higher phosphorus levels, even within the normal range, showed significant associations with high CAC and ECC, independent of kidney function (Figure). Considering presence of any calcification, results were generally consistent, although cystatin C-based eGFR <60 mL/min/1.73m2was associated with mitral valve calcification (present in 47%) (odds ratio 1.70 [95% CI 1.13, 2.58]).Conclusion:Cumulative exposure to lower eGFR showed weak associations with vascular calcification in community-dwelling older adults. Among BMM markers, phosphorus was most robustly associated with CAC and ECC beyond kidney function. Our results suggest a potential key role of phosphorus in the pathophysiology of vascular calcification.

Background and aims:Psychosocial factors such as depression, character traits, and lack of social support have been associated with increased risk of cardiovascular disease (CVD). However, data of peripheral artery disease (PAD) in this regard are sparse. Since risk factor profiles differ across atherosclerotic CVD (ASCVD) subtypes, to appreciate the contribution of psychosocial factors to overall ASCVD, we aimed to comprehensively explore the association of psychosocial factors with the risk of PAD and ASCVD in a community cohort.Methods:We included 12,090 participants from the Atherosclerosis Risk in Communities (ARIC) Study (mean age 56.7 [SD 5.7] years) free of PAD and ASCVD at baseline (1990-1992). Depressive symptom was evaluated by the Maastricht Questionnaire (MQ). Trait anger was assessed by the Spielberger Trait Anger Scale. Social support was measured by the Interpersonal Support Evaluation List, while the extent of social networks was evaluated by the Lubben Social Network Scale. PAD events were defined as hospitalizations with PAD diagnosis and procedures. ASCVD included adjudicated myocardial infarction, fatal coronary disease, and ischemic stroke events.Results:We observed 429 PAD and 2,539 ASCVD events during a median follow-up of 23.1 years. The cumulative incidence of PAD was highest in the highest quartile of MQ score. This association remained after adjusting for traditional CVD risk factors, socioeconomic status, and physical activity. A weaker association was observed for ASCVD. Social support also showed independent association with incident PAD, but not with ASCVD. Trait anger and social network were not significantly associated with either PAD or ASCVD (Table).Conclusions:Psychosocial factors demonstrated more evident associations with PAD than ASCVD. Our results suggest the importance of considering PAD when assessing the overall impact of those factors on CVD. Future studies are needed to explore potential mechanisms behind our observation.

Background:Patients with cardiac disease and stroke have a high risk of infection, and several prevention programs target those patients. However, data among patients with peripheral artery disease (PAD) are lacking.Methods:In 5,055 ARIC study participants without a preceding infection within three months of visit 5 (age 71-90 years in 2011-2013), we assessed whether PAD (clinical history or ankle-brachial index [ABI] ≤0.90) was associated with subsequent hospitalization for infections. We ascertained infections using ICD-9 codes at discharge to identify overall infection as well as its major subtypes (i.e., cellulitis, bloodstream infection, pneumonia, and urinary tract infection). We also stratified participants with PAD by history of concomitant coronary heart disease (CHD) or stroke. Multivariable Cox regression models were used to estimate adjusted hazard ratio (aHR).Results:During the median follow-up of 5.4 years, 1103 (44.4 rate per 1000 person-years) had hospitalizations with infection. As compared to those with an ABI of 1.11-1.20, participants with PAD were at greater risk of overall infection (aHR 1.67 [95% CI 1.38, 2.02], as were those with borderline low ABI (0.91-1.00) (aHR 1.89 [1.54, 2.31]). Consistent results were observed when the major subtypes of infection were explored. When we compared four groups according to PAD and CHD/stroke, PAD alone had a higher risk of infection similar to those with PAD plus CHD/stroke compared to those without PAD or CHD/stroke (Figure). Of note, PAD alone showed the highest risk of bloodstream and urinary tract infections.Conclusions:PAD and borderline low ABI were independently associated with greater risk of hospitalized infection among older adults. The contribution of PAD to elevated infection risk appeared even larger than that of CHD/stroke. Our study suggests that PAD patients should be considered for preventive strategies for infection (e.g., vaccination).

Introduction:Current research suggests racial differences exist in the utilization of guideline directed medical therapy (GDMT) and prognosis in heart failure with reduced ejection fraction (HFrEF). Whether individual and community level socioeconomic status (SES) impacts prescription patterns of GDMT and prognosis in HFrEF has not been studied.Methods:We studied 669 ARIC participants with incident HFrEF (EF<50%) (mean age 77.6 (SD 6.5) years; 39% black; 46% women) during 2005-2017 (median 1.8 years of follow-up). We assessed the proportion of patients on optimal GDMT (defined as ß-blockers [BB] and ACE inhibitors [ACEI] or angiotensin receptor blockers [ARB]) or adequate GDMT (one of either BB, ACEI/ARB, aldosterone antagonists [AA], or hydralazine and nitrates [H-ISDN]) at hospital discharge by individual SES (education and income), neighborhood SES (area deprivation index: ADI) and their combination (Table). We also examined the contribution of GDMT prescription to prognosis overall, and by SES. Subsequently, we quantified the association of SES with mortality and re-hospitalization for HFrEF.Results:The proportion of patients prescribed optimal and adequate GDMT was 54% and 81%, respectively. BB were most frequently prescribed (83%), followed by ACEI/ARB (61%), AA (11%), and H-ISDN (9%). Overall, BB were associated with lower mortality, while H-ISDN were associated with higher mortality, compared to their non-use counterparts. ACEI/ARB were associated with lower re-hospitalization, compared to non-users of ACEI/ARB. The prescription of GDMT and the effect of GDMT on prognosis did not significantly differ by SES. Despite that, lower SES was independently associated with higher risk of mortality and re-hospitalization (Table).Conclusions:Overall, optimal GDMT was low at discharge, but did not differ by SES. Despite that, there were significant differences in death and re-hospitalization by SES, suggesting a potential need for tailored approaches to HFrEF management for low SES individuals.

Introduction:Cardiovascular disease (CVD), including stroke, is a leading cause of morbidity and mortality. Ideal levels of the American Heart Association’s Life’s Simple 7 (LS7) metric are associated with lower stroke risk. However, the association between LS7 and recurrent CVD and mortality after incident stroke is unclear.Hypothesis:Stroke survivors with higher LS7 scores before incident stroke would have lower risk of recurrent CVD and mortality than those with lower scores.Methods:From 14715 individuals free of stroke at ARIC baseline (1987-1989), we analyzed data on 1380 participants who had an incident stroke between 1987-2017. A summary baseline LS7 score (range: 0-14) was derived by assigning 2 points for ideal, 1 point for intermediate, and 0 points for poor on each of the following: smoking, adiposity, physical activity, diet, total cholesterol, blood pressure and fasting glucose at baseline. We calculated adjusted hazard ratios (HR) for a composite and individual CVD outcomes of recurrent stroke, myocardial infarction, heart failure, and all-cause mortality after incident stroke, per a priori categories in baseline LS7 score.Results:At baseline, the mean age of participants with incident stroke was 55.7 ± 5.6 years (53% women, 36% black). Participants with the highest LS7 scores (≥10, n= 3287) had 66% lower risk (HR: 0.34, 95% CI: 0.29-0.40) of incident stroke than those with intermediate cardiovascular (CV) health (4-6, n=4166) (Table). During a median (SE) follow-up of 7.5 (0.45) years, 42.5% (587/1380) had recurrent composite CVD after incident stroke. LS7 score at baseline (before incident stroke) was inversely associated with recurrent CV outcomes (composite, myocardial infarction, heart failure) and all-cause mortality after incident stroke but not recurrent stroke (Table).Conclusions:Better CV health in mid-life before incident stroke was associated with lower risk of recurrent CVD after stroke, suggesting that good CV health is essential for secondary prevention among stroke patients.

Background:Peripheral artery disease (PAD) reduces physical activity, and both PAD and lower physical activity levels have been shown to increase mortality risk. Yet, their joint contributions to mortality have not been systematically studied, especially with the objective measure of physical activity.Hypothesis:PAD and lower 1-week objectively-measured physical activity are synergistically associated with mortality.Methods:We studied 7124 Hispanic adults aged 45-74 years at baseline from the Study of Latinos who adhered to an objective measure of physical activity using wearable accelerometers. We quantified the associations of the status of PAD (ankle-brachial index [ABI] ≤0.90 [PAD], 0.91-1.39 [no PAD], and ≥1.40 [possible PAD with ankle artery calcification]) and two physical activity measures (sedentary time [tertiles] and daily physical movement counts [tertiles]) at baseline with mortality using multivariable Cox models accounting for sampling weights.Results:During a median follow-up of 7.0 years, 289 participants died. Sedentary time and daily physical movement counts were weakly correlated (r=-0.17). Both low and high ABI, longer sedentary time, and lower physical movement counts were all independently associated with increased mortality risk (marginal cells in Table). In terms of the joint associations of PAD and physical activity with mortality, they generally demonstrated synergistic associations (e.g., hazard ratio 4.43 [95%CI, 2.44-8.03] in ABI ≤0.9 plus top tertile of sedentary time and 5.46 [2.47-12.08] in ABI ≥1.40 plus top tertile of sedentary time vs. normal ABI with shortest sedentary time) (cross-categories in Table), with no significant interactions.Conclusions:Both low and high ABI, and lower objectively-measured physical activity levels were significantly associated with greater risk of mortality independently of each other and potential confounders. Our results suggest the importance of objectively evaluating daily physical activity levels and leg vascular condition.

Background:Varicose veins recently attract attention in medical community due to its high prevalence and potential impact on major clinical consequences like deep venous thrombosis. Also, a few small studies (n<50) have reported that patients with varicose veins have reduced physical function than those without. However, a large study is required to quantify the association of varicose veins and reduced physical function in the community.Methods:In 6,506 ARIC participants (aged 71-90 years, 2011-2013 at visit 5), varicose veins were identified using outpatient and inpatient ICD codes from Medicare claims (sample limited to fee for service beneficiaries) or hospitalization data after visit 1 through visit 5. We assessed the cross-sectional associations of clinically recognized varicose veins with the Short Physical Performance Battery (SPPB) score (0-12) (based on the sum of scores from three components [chair stands, standing balance, and gait speed] [0-4 points each]) and frailty (frail if ≥3 of the five components [weight loss, exhaustion, low physical activity, slow walking, and grip strength].Results:There were 361 participants with a clinical diagnosis of varicose veins (124 inpatient and 256 outpatient). Varicose veins were independently associated with poor physical function (SPPB ≤6 vs. >6) (adjusted odds ratio 1.72 [95% CI 1.24, 2.37]) and with all individual components of the SPPB (Table). Similarly, varicose veins were associated with being frail (frailty ≥3 vs. <3) (adjusted odds ratio 1.76 [95%CI 1.26, 2.46]) and with only slower walking of frailty components.Conclusions:In community-dwelling older adults, persons with varicose veins had lower physical function and were more frail compared to their counterparts. Longitudinal research is warranted to explore the temporality between varicose veins and reduced physical function.