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Importance: Clonal hematopoiesis of indeterminate potential (CHIP) may contribute to the risk of atrial fibrillation (AF) through its association with inflammation and cardiac remodeling., Objective: To determine whether CHIP was associated with AF, inflammatory and cardiac biomarkers, and cardiac structural changes., Design, Setting, and Participants: This was a population-based, prospective cohort study in participants of the Atherosclerosis Risk in Communities (ARIC) study and UK Biobank (UKB) cohort. Samples were collected and echocardiography was performed from 2011 to 2013 in the ARIC cohort, and samples were collected from 2006 to 2010 in the UKB cohort. Included in this study were adults without hematologic malignancies, mitral valve stenosis, or previous mitral valve procedure from both the ARIC and UKB cohorts; additionally, participants without hypertrophic cardiomyopathy and congenital heart disease from the UKB cohort were also included. Data analysis was completed in 2023., Exposures: CHIP (variant allele frequency [VAF] ≥2%), common gene-specific CHIP subtypes (DNMT3A, TET2, ASXL1), large CHIP (VAF ≥10%), inflammatory and cardiac biomarkers (high-sensitivity C-reactive protein, interleukin 6 [IL-6], IL-18, high-sensitivity troponin T [hs-TnT] and hs-TnI, N-terminal pro-B-type natriuretic peptide), and echocardiographic indices., Main Outcome Measure: Incident AF., Results: A total of 199 982 adults were included in this study. In ARIC participants (4131 [2.1%]; mean [SD] age, 76 [5] years; 2449 female [59%]; 1682 male [41%]; 935 Black [23%] and 3196 White [77%]), 1019 had any CHIP (24.7%), and 478 had large CHIP (11.6%). In UKB participants (195 851 [97.9%]; mean [SD] age, 56 [8] years; 108 370 female [55%]; 87 481 male [45%]; 3154 Black [2%], 183 747 White [94%], and 7971 other race [4%]), 11 328 had any CHIP (5.8%), and 5189 had large CHIP (2.6%). ARIC participants were followed up for a median (IQR) period of 7.0 (5.3-7.7) years, and UKB participants were followed up for a median (IQR) period of 12.2 (11.3-13.0) years. Meta-analyzed hazard ratios for AF were 1.12 (95% CI, 1.01-1.25; P = .04) for participants with vs without large CHIP, 1.29 (95% CI, 1.05-1.59; P = .02) for those with vs without large TET2 CHIP (seen in 1340 of 197 209 [0.67%]), and 1.45 (95% CI, 1.02-2.07; P = .04) for those with vs without large ASXL1 CHIP (seen in 314 of 197 209 [0.16%]). Large TET2 CHIP was associated with higher IL-6 levels. Additionally, large ASXL1 was associated with higher hs-TnT level and increased left ventricular mass index., Conclusions and Relevance: Large TET2 and ASXL1, but not DNMT3A, CHIP was associated with higher IL-6 level, indices of cardiac remodeling, and increased risk for AF. Future research is needed to elaborate on the mechanisms driving the associations and to investigate potential interventions to reduce the risk.

Background: There are several studies that have analyzed disparities in cardiovascular disease (CVD) health using a variety of different administrative databases; however, a unified analysis of major databases does not exist. In this analysis of multiple publicly available datasets, we sought to examine racial and ethnic disparities in different aspects of CVD, CVD-related risk factors, CVD-related morbidity and mortality, and CVD trainee representation in the US., Methods: We used National Health and Nutrition Examination Survey, National Ambulatory Medical Care Survey, National Inpatient Sample, Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research, United Network for Organ Sharing, and American Commission for Graduate Medical Education data to evaluate CVD-related disparities among Non-Hispanic (NH) White, NH Black and Hispanic populations., Results: The prevalence of most CVDs and associated risk factors was higher in NH Black adults compared to NH White adults, except for dyslipidemia and ischemic heart disease (IHD). Statins were underutilized in IHD in NH Black and Hispanic patients. Hospitalizations for HF and stroke were higher among Black patients compared to White patients. All-cause, CVD, heart failure, acute myocardial infarction, IHD, diabetes mellitus, hypertension and cerebrovascular disease related mortality was highest in NH Black or African American individuals. The number of NH Black and Hispanic trainees in adult general CVD fellowship programs was disproportionately lower than NH White trainees., Conclusion: Racial disparities are pervasive across the spectrum of CVDs with NH Black adults at a significant disadvantage compared to NH White adults for most CVDs., (Copyright © 2024 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the epidemiology and prognostic value of coronary artery calcium (CAC) in individuals with prediabetes., Research Design and Methods: We pooled participants free of clinical atherosclerotic cardiovascular disease (ASCVD) from four prospective cohorts: the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. Two definitions were used for prediabetes: inclusive (fasting plasma glucose [FPG] ≥100 to <126 mg/dL and hemoglobin A1c [HbA1c] ≥5.7% to <6.5%, if available, and no glucose-lowering medications) and restrictive (FPG ≥110 to <126 mg/dL and HbA1c ≥5.7% to <6.5%, if available, among participants not taking glucose-lowering medications)., Results: The study included 13,376 participants (mean age 58 years; 54% women; 57% White; 27% Black). The proportions with CAC ≥100 were 17%, 22%, and 37% in those with euglycemia, prediabetes, and diabetes, respectively. Over a median (25th-75th percentile) follow-up time of 14.6 (interquartile range 7.8-16.4) years, individuals with prediabetes and CAC ≥100 had a higher unadjusted 10-year incidence of ASCVD (13.4%) than the overall group of those with diabetes (10.6%). In adjusted analyses, using the inclusive definition of prediabetes, compared with euglycemia, the hazard ratios (HRs) for ASCVD were 0.79 (95% CI 0.62, 1.01) for prediabetes and CAC 0, 0.70 (0.54, 0.89) for prediabetes and CAC 1-99, 1.54 (1.27, 1.88) for prediabetes and CAC ≥100, and 1.64 (1.39, 1.93) for diabetes. Using the restrictive definition, the HR for ASCVD was 1.63 (1.29, 2.06) for prediabetes and CAC ≥100., Conclusions: CAC ≥100 is frequent among individuals with prediabetes and identifies a high ASCVD risk subgroup in which the adjusted ASCVD risk is similar to that in individuals with diabetes., (© 2024 by the American Diabetes Association.)

Competing Interests: Conflict of interest: None declared.

Background: It is unclear how metabolic syndrome (MetS) and diabetes affect Gal-3 (galectin 3) levels and the resulting implications for heart failure (HF) risk. We assessed relationships of MetS and diabetes with Gal-3, and their joint associations with incident HF., Methods and Results: We included 8445 participants without HF (mean age, 63 years; 59% men; 16% Black race) at ARIC (Atherosclerosis Risk in Communities) study visit 4 (1996-1999). We categorized participants as having MetS only, MetS with diabetes, or neither, and by quartiles of MetS severity Z score. We assessed cross-sectional associations of metabolic risk categories with high Gal-3 level (≥75th percentile) using logistic regression. We used Cox regression to evaluate combined associations of metabolic risk categories and Gal-3 quartiles with HF. In cross-sectional analyses, compared with no MetS and no diabetes, MetS only (odds ratio [OR], 1.24 [95% CI, 1.10-1.41]) and MetS with diabetes (OR, 1.59 [95% CI, 1.32-1.92]) were associated with elevated Gal-3. Over a median follow-up of 20.5 years, there were 1749 HF events. Compared with individuals with neither diabetes nor MetS and with Gal-3 in the lowest quartile, the combination of MetS with diabetes and Gal-3 ≥75th percentile was associated with a 4-fold higher HF risk (hazard ratio, 4.35 [95% CI, 3.30-5.73]). Gal-3 provided HF prognostic information above and beyond MetS, NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T, and CRP (C-reactive protein) (ΔC statistic for models with versus without Gal-3: 0.003; P =0.004)., Conclusions: MetS and diabetes are associated with elevated Gal-3. The HF risk significantly increased with the combination of greater metabolic risk and higher Gal-3.

Background: Among individuals with hypertension and low diastolic blood pressure (DBP), the optimal BP target remains controversial due to concerns that BP lowering may reduce coronary perfusion. We determined the impact of intensive BP control among individuals with elevated systolic BP who have low DBP and elevated hs-cTnT (high-sensitivity cardiac troponin T) levels., Methods and Results: A total of 8828 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were stratified by baseline DBP. Those with low DBP (<70 mm Hg) were further stratified by elevated hs-cTnT (≥14 ng/L) at baseline. The effects of intensive versus standard BP lowering on a cardiovascular disease composite end point, all-cause death, and 1-year change in hs-cTnT were determined. The combination of low DBP/high hs-cTnT was independently associated with a higher risk for cardiovascular disease and all-cause death, as well as greater 1-year increases in hs-cTnT, compared with DBP ≥70 mm Hg. However, randomization to intensive versus standard BP lowering led to similar reductions in cardiovascular disease risk among individuals with low DBP/high hs-cTnT (hazard ratio [HR], 0.82 [95% CI, 0.57-1.19]), low DBP/low hs-cTnT (HR, 0.48 [95% CI, 0.29-0.79]), and DBP ≥70 mm Hg (HR, 0.73 [95% CI, 0.60-0.89]; P for interaction=0.20). Intensive BP lowering also led to a reduction in all-cause death that was similar across groups ( P for interaction=0.57)., Conclusions: In this nonprespecified subgroup analysis of SPRINT, individuals with low DBP and elevated hs-cTnT, low DBP and nonelevated hs-cTnT, and DBP ≥70 mm Hg derived similar cardiovascular disease and mortality benefits from intensive BP lowering. These findings warrant confirmation in other studies.

Background: Cardiac troponins are associated with adverse cardiovascular disease (CVD) outcomes. The value of high-sensitivity cardiac troponin I (hs-cTnI) independently and in concert with troponin T (hs-cTnT) in the management of hypertension has not been well studied., Methods: We assessed the utility of hs-cTnI independently and with hs-cTnT in identifying the highest risk individuals in the Systolic Blood Pressure Intervention Trial (SPRINT). Among 8796 eligible SPRINT participants, hs-cTnI was measured at baseline and 1 year. The association of baseline level and 1-year change in hs-cTnI with CVD events and all-cause death was evaluated using adjusted Cox regression models. We further assessed the complementary value of hs-cTnI and hs-cTnT by identifying concordant and discordant categories and assessing their association with outcomes., Results: hs-cTnI was positively associated with composite CVD risk [myocardial infarction, other acute coronary syndrome, stroke, or cardiovascular death: hazard ratio 1.23, 95% confidence interval 1.08-1.39 per 1-unit increase in log(troponin I)] independent of traditional risk factors, N-terminal pro-B-type natriuretic peptide, and hs-cTnT. Intensive blood pressure lowering was associated with greater absolute risk reduction (4.5% vs 1.7%) and lower number needed to treat (23 vs 59) for CVD events among those with higher baseline hs-cTnI (≥6 ng/L in men, ≥4 ng/L in women). hs-cTnI increase at 1 year was also associated with increased CVD risk. hs-cTnI and hs-cTnT were complementary, and elevations in both identified individuals with the highest risk for CVD and death., Conclusions: Baseline levels and change in hs-cTnI over 1 year identified higher-risk individuals who may derive greater cardiovascular benefit with intensive blood pressure treatment. hs-TnI and hs-TnT have complementary value in CVD risk assessment. ClinicalTrials.gov Registration Number: NCT01206062., (© Association for Diagnostics & Laboratory Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The association of social vulnerability and cardiovascular disease-related mortality in older adults has not been well characterized., Methods: The Centers for Disease Control and Prevention database was evaluated to examine the relationship between county-level Social Vulnerability Index (SVI) and age-adjusted cardiovascular disease-related mortality rates (AAMRs) in adults aged 65 and above in the United States between 2016 and 2020., Results: A total of 3139 counties in the United States were analyzed. Cardiovascular disease-related AAMRs increased in a stepwise manner from first (least vulnerable) to fourth SVI quartiles; (AAMR of 2423, 95% CI [confidence interval] 2417-2428; 2433, 95% CI 2429-2437; 2516, 95% CI 2513-2520; 2660, 95% CI 2657-2664). Similar trends among AAMRs were noted based on sex, all race and ethnicity categories, and among urban and rural regions. Higher AAMR ratios between the highest and lowest SVI quartiles, implying greater relative associations of SVI on mortality rates, were seen among Hispanic individuals (1.52, 95% CI 1.49-1.55), Non-Hispanic-Asian and Pacific Islander individuals (1.32, 95% CI 1.29-1.52), Non-Hispanic- American Indian or Alaskan Native individuals (1.43, 95% CI 1.37-1.50), and rural counties (1.21, 95% CI 1.20-1.21)., Conclusion: Social vulnerability as measures by the SVI was associated with cardiovascular disease-related mortality in older adults, with the association being particularly prominent in ethnic minority patients and rural counties., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Diagnosing and assessing the risk of peripheral artery disease (PAD) has long been a focal point for medical practitioners. The impaired blood circulation in PAD patients results in altered microvascular perfusion patterns in the calf muscles which is the primary location of intermittent claudication pain. Consequently, we hypothesized that changes in perfusion and increase in connective tissue could lead to alterations in the appearance or texture patterns of the skeletal calf muscles, as visualized with non-invasive imaging techniques. We designed an automatic pipeline for textural feature extraction from contrast-enhanced magnetic resonance imaging (CE-MRI) scans and used the texture features to train machine learning models to detect the heterogeneity in the muscle pattern among PAD patients and matched controls. CE-MRIs from 36 PAD patients and 20 matched controls were used for preparing training and testing data at a 7:3 ratio with cross-validation (CV) techniques. We employed feature arrangement and selection methods to optimize the number of features. The proposed method achieved a peak accuracy of 94.11% and a mean testing accuracy of 84.85% in a 2-class classification approach (controls vs. PAD). A three-class classification approach was performed to identify a high-risk PAD sub-group which yielded an average test accuracy of 83.23% (matched controls vs. PAD without diabetes vs. PAD with diabetes). Similarly, we obtained 78.60% average accuracy among matched controls, PAD treadmill exercise completers, and PAD exercise treadmill non-completers. Machine learning and imaging-based texture features may be of interest in the study of lower extremity ischemia., (Copyright © 2023 Elsevier Inc. All rights reserved.)

National estimates of deaths related to both heart failure (HF) and sleep apnea (SA) are not known. We evaluated the trends in HF and SA related mortality using the CDC-WONDER database in adults aged ≥25 years in the US. All deaths related to HF and SA as contributing or underlying causes of death were queried. Between 1999 and 2019, there were a total of 6,484,486 deaths related to HF, 204,824 deaths related to SA, and 53,957 deaths related to both. There was a statistically significant increase in the age-adjusted mortality rate (AAMR) for both SA-related (average annual percent change [AAPC] 8.2%) and combined HF and SA- related (AAPC 10.1 %) deaths. Men had consistently higher AAMRs compared with women, and both groups had a similar increasing trend in AAMR. Non-Hispanic (NH) Black individuals had the highest HF and SA-related AAMR, followed by NH White and Hispanic/Latino individuals. Adults aged >75 years consistently had the highest AAMR with the steepest increase (AAPC 11.1%). In conclusion, HF and SA-related mortality has significantly risen over the past two decades with the elderly, men, and NH Black at disproportionately higher risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare.

Heart failure (HF) is a global pandemic affecting over 64 million people worldwide. Its prevalence is on an upward trajectory, with associated increasing healthcare expenditure. Organizations including the American College of Cardiology (ACC) and the American Heart Association (AHA) have identified HF prevention as an important focus. Recently, the ACC/AHA/Heart Failure Society of America (HFSA) Guidelines on heart failure were updated with a new Class IIa, Level of Evidence B recommendation for biomarker-based screening in patients at risk of developing heart failure. In this review, we evaluate the studies that have assessed the various roles and contributions of biomarkers in the prediction and prevention of heart failure. We examined studies that have utilized biomarkers to detect cardiac dysfunction or abnormality for HF risk prediction and screening before patients develop clinical signs and symptoms of HF. We also included studies with biomarkers on prognostication and risk prediction over and above existing HF risk prediction models and studies that address the utility of changes in biomarkers over time for HF risk. We discuss studies of biomarkers to guide management and assess the efficacy of prevention strategies and multi-biomarker and multimodality approaches to improve risk prediction.

Background: Longitudinal associations of noninvasive 2-dimensional phase-contrast magnetic resonance imaging (2D-PC-MRI) velocity markers of the superficial femoral artery (SFA) were analyzed along with the characteristics of peripheral artery disease (PAD). We hypothesized that the 2-year differences in MRI-based measures of SFA velocity were associated with longitudinal changes in markers of PAD., Methods: A total of 33 (11 diabetic, 22 nondiabetic) patients with PAD with baseline and 2-year follow-up MRI scans were included in this secondary analysis of the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Electrocardiographically gated 2D-PC-MRI was performed at a proximal and a distal location of the distal SFA territory. SFA lumen, wall, and total vessel volumes and the normalized wall index (NWI) were analyzed., Results: Baseline characteristics did not differ between diabetic and nondiabetic PAD patients. Maximum proximal and distal SFA velocity measures did not differ between baseline and 2 years (41.98 interquartile range (IQR) (23.58-72.6) cm/s vs. 40.31 IQR (26.69-61.29) cm/s; P = 0.30). Pooled analysis (N = 33) showed that the 24-month change in the NWI was inversely associated with the 24-month change in the proximal maximal SFA velocity (beta = -168.36, R2 = 0.150, P value = 0.03). The 24-month change of the maximum velocity differences between the proximal and distal SFA locations was inversely associated with the 24-month changes in peak walking distance (beta = -0.003, R2 = 0.360, P value = 0.011)., Conclusion: The 2-year change of SFA plaque burden is inversely associated with the 2-year change of proximal peak SFA blood flow velocity. 2D-PC-MRI measured SFA velocity may be of interest in assessing PAD longitudinally., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global cardiovascular disease (CVD), atrial fibrillation (AF), and death in older adults., Methods and Results: Participants from Atherosclerosis Risk in Communities study Visit 5 (mean age 75.4 ± 5.1 years) with IL-6 and IL-18 measurements were included (n = 5672). Cox regression models were used to assess associations of IL-6 and IL-18 with coronary heart disease (CHD), ischaemic stroke, heart failure (HF) hospitalization, global CVD (composite of CHD, stroke, and HF), AF, and all-cause death. Over a median follow-up of 7.2 years, there were 1235 global CVD events, 530 AF events, and 1173 deaths. Higher IL-6 [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.44-1.72 per log unit increase] and IL-18 (HR 1.13, 95% CI 1.01-1.26) were significantly associated with global CVD after adjustment for cardiovascular risk factors. Association between IL-6 and global CVD remained significant after further adjustment for high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT) but was no longer significant for IL-18 after further adjustments. Interleukin-6 was also associated with increased risk for CHD, HF, and AF after adjustment for covariates. Both IL-6 and IL-18 were associated with increased risk for all-cause death independent of cardiovascular risk factors and other biomarkers., Conclusion: Among older adults, both IL-6 and IL-18 were associated with global CVD and death. The association between IL-6 with CVD appears to be more robust and was independent of hs-CRP, NT-proBNP, and hs-TnT., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: MMP (matrix metalloproteinase)-2 participates in extracellular matrix regulation and may be involved in heart failure (HF), atrial fibrillation (AF), and coronary heart disease., Methods: Among the 4693 ARIC study (Atherosclerosis Risk in Communities) participants (mean age, 75±5 years; 42% women) without prevalent HF, multivariable Cox proportional hazard models were used to estimate associations of plasma MMP-2 levels with incident HF, HF with preserved ejection fraction (≥50%), HF with reduced ejection fraction (<50%), AF, and coronary heart disease. Mediation of the association between MMP-2 and HF was assessed by censoring participants who developed AF or coronary heart disease before HF. Multivariable linear regression models were used to assess associations of MMP-2 with measures of left ventricular and left atrial structure and function., Results: Compared with the 3 lower quartiles, the highest MMP-2 quartile associated with greater risk of incident HF overall (adjusted hazard ratio, 1.48 [95% CI, 1.21-1.81]), incident HF with preserved ejection fraction (1.44 [95% CI, 1.07-1.94]), incident heart failure with reduced ejection fraction (1.48 [95% CI, 1.08-2.02]), and incident AF (1.44 [95% CI, 1.18-1.77]) but not incident coronary heart disease (0.97 [95% CI, 0.71-1.34]). Censoring AF attenuated the MMP-2 association with HF with preserved ejection fraction. Higher plasma MMP-2 levels were associated with larger left ventricular end-diastolic volume index, greater left ventricular mass index, higher E/e' ratio, larger left atrial volume index, and worse left atrial reservoir and contractile strains (all P <0.001)., Conclusions: Higher plasma MMP-2 levels associate with diastolic dysfunction, left atrial dysfunction, and a higher risk of incident HF and AF. AF is a mediator of MMP-2-associated HF with preserved ejection fraction risk., Competing Interests: Disclosures Dr Hoogeveen reports research support and consultation fees not related to this study from Denka Seiken. Dr Shah reports research support not related to this study from Novartis and Philips Ultrasound and consulting fees from Philips Ultrasound. The other authors report no conflicts.

Introduction: Although lower socioeconomic status (SES) has been associated with worse in-hospital outcomes among patients with heart failure, the in-hospital outcomes for patients undergoing durable Left Ventricular Assist Device (LVAD) implantation or Heart Transplantation (HT) based on SES have not been well characterized., Methods: We analyzed data from the National Inpatient Sample of hospitalizations between January 2016 and December 2020 of patients aged 18 and over who underwent a HT or newly implanted LVAD. Quartile classification of the median household income of the patient's residential zip code was used to estimate SES. Multivariable analyses with logistic and linear regression were used to evaluate the effects of SES on inpatient outcomes including inpatient mortality, length of stay, and key inpatient complications., Results: A total of 16,265 weighted hospitalizations for new LVAD implantation and 14,320 weighted hospitalizations for HT were identified. In multivariable analysis, among patients undergoing HT or LVAD implantation respectively, there were no significant differences between the lowest and highest SES quartiles among important in-hospital outcomes including length of stay (adj B-coeff .56, (-3.59)-(4.71), p = .79 and adj B-coeff 2.40, (-.21)-(5.02), p = .07) and mortality (aOR 1.02, .61-1.70, p = .94 and aOR 1.08, .72-1.62, p = .73). There were also no differences based on SES quartile in important inpatient complications including stroke and cardiac arrest., Conclusion: In this analysis from the National Inpatient Sample, we demonstrate that SES, evaluated by median zip code income, was not associated with important in-hospital metrics including mortality and length of stay among patients undergoing LVAD or HT., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Aims: In clinical practice, factors associated with cardiovascular disease (CVD) like albuminuria, education level, or coronary artery calcium (CAC) are often known, but not incorporated in cardiovascular risk prediction models. The aims of the current study were to evaluate a methodology for the flexible addition of risk modifying characteristics on top of SCORE2 and to quantify the added value of several clinically relevant risk modifying characteristics., Methods and Results: Individuals without previous CVD or DM were included from the UK Biobank; Atherosclerosis Risk in Communities (ARIC); Multi-Ethnic Study of Atherosclerosis (MESA); European Prospective Investigation into Cancer, The Netherlands (EPIC-NL); and Heinz Nixdorf Recall (HNR) studies (n = 409 757) in whom 16 166 CVD events and 19 149 non-cardiovascular deaths were observed over exactly 10.0 years of follow-up. The effect of each possible risk modifying characteristic was derived using competing risk-adjusted Fine and Gray models. The risk modifying characteristics were applied to individual predictions with a flexible method using the population prevalence and the subdistribution hazard ratio (SHR) of the relevant predictor. Risk modifying characteristics that increased discrimination most were CAC percentile with 0.0198 [95% confidence interval (CI) 0.0115; 0.0281] and hs-Troponin-T with 0.0100 (95% CI 0.0063; 0.0137). External validation was performed in the Clinical Practice Research Datalink (CPRD) cohort (UK, n = 518 015, 12 675 CVD events). Adjustment of SCORE2-predicted risks with both single and multiple risk modifiers did not negatively affect calibration and led to a modest increase in discrimination [0.740 (95% CI 0.736-0.745) vs. unimproved SCORE2 risk C-index 0.737 (95% CI 0.732-0.741)]., Conclusion: The current paper presents a method on how to integrate possible risk modifying characteristics that are not included in existing CVD risk models for the prediction of CVD event risk in apparently healthy people. This flexible methodology improves the accuracy of predicted risks and increases applicability of prediction models for individuals with additional risk known modifiers., Competing Interests: Conflict of interest: Dr. Matsushita received funding from the National Institutes of Health during the study and personal fees from Fukuda Denshi, Kowa Company, and the American Medical Group Association outside of the submitted work. L.P. is funded by a BHF Programme Grant (RG/18/13/33946) S.K. is funded by a BHF Chair award (CH/12/2/29428)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking., Methods: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality., Results: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6)., Conclusions: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.)., (Copyright © 2023 Massachusetts Medical Society.)

We sought to determine how biomarkers known to be associated with hypertension-induced end-organ injury complement the use of systolic blood pressure (SBP) for cardiovascular disease (CVD) risk prediction at different ages. Using data from visits 2 (1990 to 1992) and 5 (2011 to 2013) of the Atherosclerosis Risk in Communities (ARIC) study, 3 models were used to predict CVD (composite of coronary heart disease, stroke, and heart failure). Model A included traditional risk factors (TRFs) except SBP, model B-TRF plus SBP, and model C-TRF plus biomarkers (high-sensitivity troponin T [hsTnT] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]). Harrel's C-statistics were used to assess risk discrimination for CVD comparing models B and A and C and B. At visit 2, the addition of SBP to TRF (model B vs model A) significantly improved the C-statistic (∆C-statistic, 95% confidence interval 0.010, 0.007 to 0.013) whereas the addition of hsTnT to TRF (model C vs model B) decreased the C-statistic (∆C-statistic -0.0038, -0.0075 to -0.0001) compared with SBP. At visit 5, the addition of SBP to TRF did not significantly improve the C-statistic (∆C-statistic 0.001, -0.002 to 0.005) whereas the addition of both hsTnT and NT-proBNP to TRF significantly improved the C-statistic compared with SBP (∆C-statistic 0.028, 0.015 to 0.041 and 0.055, 0.036 to 0.074, respectively). In summary, the incremental value of SBP for CVD risk prediction diminishes with age whereas the incremental value of hsTnT and NT-proBNP increases with age., Competing Interests: Declaration of Competing Interest Dr. de Lemos reports grant support from Roche Diagnostics and Abbott Diagnostics, consulting fees from Ortho Clinical Diagnostics, Quidel Cardiovascular, Inc., Beckman Coulter, Siemens Health Care Diagnostics, Astra Zeneca, Novo Nordisc. Eli Lilly, Regeneron, and Amgen; and has been named a co-owner on a patent awarded to the University of Maryland (United States Patent Application Number: 15/309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure.” Dr Ballantyne has received grant/research support from and is a consultant for Abbott Diagnostic and Roche Diagnostic. The remaining authors have no competing interests to declare., (Published by Elsevier Inc.)

Objectives: The objective of this study was to evaluate the interaction between obesity and obstructive sleep apnea on acute MI in hospital mortality., Methods: This retrospective cohort study utilized Veterans Health Administration data from years 1999-2020. Participants were categorized according to their body mass index (BMI) to non-obese (BMI <30) and obese (BMI ≥30) groups. Clinical obstructive sleep apnea (SA) diagnosis was confirmed using ICD9/10 codes and the study subgroups included non-obese with no obstructive sleep apnea (nOB-nSA), non-Obese with obstructive sleep apnea (nOB-SA), obese with no obstructive sleep apnea (OB-nSA), and obese with obstructive sleep apnea (OB-SA). The primary outcome was odds ratio of in-hospital mortality during the hospitalization with acute MI as the principal diagnosis adjusted for age, gender, race, ethnicity, and Charlson comorbidity index (CCI) with the nOB-nSA group as the comparison group., Results: Among 72,036 veterans with acute-MI hospitalization, individuals with obesity and obstructive sleep apnea (OB-SA) had the lowest in-hospital mortality rate (1.0%) compared to those without obesity and obstructive sleep apnea (nOB-nSA, 2.8%), with obesity but without obstructive sleep apnea (OB-nSA, 2.4%), and with obesity and obstructive sleep apnea (nOB-SA, 1.4%). The adjusted odds ratio for mortality, compared to nOB-nSA, was 9% higher but not significant in OB-nSA (aOR, 1.09, 95%CI: 0.95, 1.25), 46% lower in OB-nSA (aOR, 0.54, 95%CI: 0.45, 0.66), and 52% lower in OB-SA (aOR, 0.48: 95%CI: 0.41, 0.57)., Conclusion: Our data suggest that the association between obesity and improved survival in acute MI is largely driven by the presence of sleep apnea., Competing Interests: Declaration of competing interest Authors declare none., (Published by Elsevier B.V.)

Introduction: The 2017 American College of Cardiology/American Heart Association blood pressure guideline redefined hypertension and lowered the blood pressure treatment target. Empirical data on the guideline's impact are needed., Methods: Data were analyzed from Atherosclerosis Risk in Communities study participants who attended baseline pre-guideline (2016-2017) and post-guideline (2018-2019) visits with baseline systolic blood pressure between 120 and 159 mmHg. Participants were grouped according to baseline systolic blood pressure by change in classification under the new guideline as follows: not reclassified (120-129 mmHg), reclassified to Stage 1 hypertension (130-139 mmHg), and reclassified to Stage 2 hypertension (140-159 mmHg). Means and 95% CIs for systolic blood pressure changes between baseline and follow-up, changes in antihypertensive use, and percentages that achieved the post-guideline recommendation (systolic blood pressure <130 mmHg) were calculated. Analyses were performed in 2021-2022., Results: Among 2,193 community-dwelling Atherosclerosis Risk in Communities participants aged 71-95 years at baseline, systolic blood pressure changes between baseline and follow-up visits differed among participants not reclassified (+4.1 mmHg, 95% CI=3.0, 5.3 mmHg), reclassified to Stage 1 hypertension (-1.1 mmHg, 95% CI= -2.2, 0.1 mmHg), and reclassified to Stage 2 hypertension (-5.7 mmHg, 95% CI= -6.8, -4.7 mmHg). Antihypertensive use changed from 77.3% to 78.4% (p=0.25) among participants reclassified to Stage 1 hypertension and from 78.3% to 81.4% (p<0.01) among participants reclassified to Stage 2 hypertension. At follow-up, 41.8% of the Stage 1 and 22.4% of the Stage 2 hypertension groups reached the systolic blood pressure <130 mmHg goal., Conclusions: There were small decreases in systolic blood pressure and increases in antihypertensive therapy among older adults reclassified to Stage 2 hypertension but not among those reclassified to Stage 1 hypertension by the 2017 American College of Cardiology/American Heart Association guideline., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Approximately 1.28 billion people are affected by hypertension globally and the incidence of hypertension is on an upward trajectory with an aging population and increasing burden of risk factors including obesity. Despite low-cost, highly-effectively, easy-to-treat strategies, it is estimated that ∼720 million people are not receiving the treatment they need for optimal hypertension management. Several factors contribute to this including an unwillingness to be treated for an asymptomatic condition., Recent Findings: Biomarkers such as troponin, B-type Natriuretic Peptide (BNP), N-terminal-pro hormone BNP (NT-proBNP), uric acid, microalbuminuria have been found to be associated with adverse clinical outcomes among individuals with hypertension. Biomarkers also allow for identification of asymptomatic organ damage., Summary: Biomarkers have the ability to identify higher risk individuals in whom risk-benefit for therapies may be most favorable, helping optimize the net benefit of therapy. Whether biomarkers can help guide therapy intensity and choice remains to be tested., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Multiple clinical trials have demonstrated significant cardiovascular benefit with use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2DM) and heart failure (HF) irrespective of ejection fraction. There are limited data evaluating real-world prescription and practice patterns of SGLT2 inhibitors., Objectives: The authors sought to assess utilization rates and facility-level variation in the use among patients with established atherosclerotic cardiovascular disease (ASCVD), HF, and T2DM using data from the nationwide Veterans Affairs health care system., Methods: The authors included patients with established ASCVD, HF, and T2DM seen by a primary care provider between January 1, 2020, and December 31, 2020. They assessed the use of SGLT2 inhibitors and the facility-level variation in their use. Facility-level variation was computed using median rate ratios, a measure of likelihood that 2 random facilities differ in use of SGLT2 inhibitors., Results: Among 105,799 patients with ASCVD, HF, and T2DM across 130 Veterans Affairs facilities, 14.6% received SGLT2 inhibitors. Patients receiving SGLT2 inhibitors were younger men with higher hemoglobin A1c and estimated glomerular filtration rate and were more likely to have HF with reduced ejection fraction and ischemic heart disease. There was significant facility-level variation of SGLT2 inhibitor use, with an adjusted median rate ratio of 1.55 (95% CI: 1.46-1.64), indicating a 55% residual difference in SGLT2 inhibitor use among similar patients with ASCVD, HF, and T2DM receiving care at 2 random facilities., Conclusions: Utilization rates of SGLT2 inhibitors are low in patients with ASCVD, HF, and T2DM, with high residual facility-level variation. These findings suggest opportunities to optimize SGLT2 inhibitor use to prevent future adverse cardiovascular events., Competing Interests: Funding Support and Author Disclosures This work was supported by a Department of Veterans Affairs (VA) Health Services Research and Development Service Investigator Initiated grants (IIR 16-072, IIR 19-069) and the Houston VA Health Services Research and Development Center for Innovations grant (CIN13-413). Support for VA/Centers for Medicare and Medicaid Services data was provided by the Department of Veterans Affairs, VA Health Services Research and Development Service, VA Information Resource Center (Project Numbers SDR 02-237 and 98-004). Dr Nambi was the site primary investigator for the study sponsored by Merck and Amgen. Dr Ballantyne has received grant/research support (to his institution) from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostic; and has been a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Matinas BioPharma Inc, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo. Dr Slipczuk has received consulting honoraria from Amgen, Regeneron, and Phillips and grant support from Amgen. Dr Bozkurt has received consulting fees from Amgen, scPharmaceuticals, Baxter, Sanofi-Aventis, Relypsa, Vifor, Roche, Boehringer Ingelheim, the Clinical Event Committee for Abbott Vascular, the Data Safety Monitoring Committees of Liva Nova and Cardurion, and the Steering Committee of Renovocor. Dr Virani has received research funding from the Department of Veterans Affairs, National Institutes of Health, World Heart Federation, and Tahir and Jooma Family; and has received an honorarium from American College of Cardiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

The predictive ability of coronary heart disease (CHD) and ischemic stroke (IS) polygenic risk scores (PRS) have been evaluated individually, but whether they predict the combined outcome of atherosclerotic cardiovascular disease (ASCVD) remains insufficiently researched. It is also unclear whether associations of the CHD and IS PRS with ASCVD are independent of subclinical atherosclerosis measures. 7,286 White and 2,016 Black participants from the population-based Atherosclerosis Risk in Communities study who were free of cardiovascular disease and type 2 diabetes at baseline were included. We computed previously validated CHD and IS PRS consisting of 1,745,179 and 3,225,583 genetic variants, respectively. Cox proportional hazards models were used to test the association between each PRS and ASCVD, adjusting for traditional risk factors, ankle-brachial index, carotid intima media thickness, and carotid plaque. The hazard ratios (HR) for the CHD and IS PRS were significant with HR of 1.50 (95% CI: 1.36-1.66) and 1.31 (95% CI: 1.18-1.45) respectively for the risk of incident ASCVD per standard deviation increase in CHD and IS PRS among White participants after adjusting for traditional risk factors. The HR for the CHD PRS was not significant with an HR of 0.95 (95% CI: 0.79-1.13) for the risk of incident ASCVD in Black participants. The HR for the IS PRS was significant with an HR of 1.26 (95%CI: 1.05-1.51) for the risk of incident ASCVD in Black participants. The association of the CHD and IS PRS with ASCVD was not attenuated in White participants after adjustment for ankle-brachial index, carotid intima media thickness, and carotid plaque. The CHD and IS PRS do not cross-predict well, and predict better the outcome for which they were created than the composite ASCVD outcome. Thus, the use of the composite outcome of ASCVD may not be ideal for genetic risk prediction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Purpose of Review: We review the limitations of current approaches for predicting Coronary Artery Disease (CAD) in young adults and explore the alternative approaches identify high-risk individuals in this population., Recent Findings: Atherosclerosis begins in childhood, and young individuals with genetic predisposition and individuals with early exposure to traditional and non-traditional risk factors have an increased lifetime risk of CAD. However, most risk prediction models have been developed and validated in middle and older age groups and focus on short-term risk. Therefore, alternative approaches are needed in younger individuals. Genetic scores, biomarkers, imaging studies, and multi-omics data all have the potential to be used and help identify high-risk individuals., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: While the longer-term Obstructive Sleep apnea (OSA)-related intermittent hypoxia (IH) leads to various comorbidities, it has become increasingly evident that OSA confers protective advantages during and after acute myocardial infarction (AMI). We hypothesized in patients who were admitted with acute MI, the presence of OSA is associated with lower in-hospital mortality compared to those without a prior diagnosis of OSA., Methods: In this nationwide retrospective study utilizing Veterans Health Administration records, we included patients hospitalized for MI with a history of sleep disorders from 1999 to 2020. We divided patients into two cohorts: those with OSA and those without OSA. The primary outcome was in-hospital mortality during AMI hospitalization. We analyzed the data using logistic regression and calculated the odds ratio of in-hospital mortality., Results: Out of more than four million veterans with any sleep diagnosis, 76,359 patients were hospitalized with a diagnosis of AMI. We observed 30,116 with OSA (age, 64 ± 10 years; BMI, 33 ± 7 kg/m 2 ) and 43,480 without OSA (age, 68 ± 12 years; BMI, 29 ± 6 kg/m 2 ). The aOR of in-patient mortality (n = 333 (1.1%)) was lower in those with OSA (aOR, 0.43; 95% CI, 0.38 to 0.49) compared to without-OSA (n = 1,102, 2.5%). However, the OSA cohort had a higher proportion of the prolonged length of stay (28.1%)., Conclusions: Presence of OSA is associated with lower in-hospital mortality among patients admitted for AMI, after adjusting for various demographic and co-morbidity factors. This study highlights the complex relationship between OSA and cardiovascular health and highlights the need for further research in this area., Competing Interests: Conflict of interest The authors report NO conflict of interests relevant to this work., (Published by Elsevier Ltd.)

Background: The recent heart failure (HF) guideline recommends the inclusion of cardiac biomarkers in defining Stage B HF., Objectives: The authors evaluated the impact of incorporating cardiac biomarkers to reclassify HF in 5,324 participants (mean age: 75.8 years) without prevalent HF enrolled in the ARIC (Atherosclerosis Risk In Communities) study and assessed prognosis of Stage B using cardiac biomarkers., Methods: Using N-terminal pro-B-type natriuretic peptide (<125 pg/mL or ≥125 pg/mL), high-sensitivity troponin T (<14 ng/L or ≥14 ng/L), and abnormal cardiac structure/function by echocardiography, individuals were classified as Stage A new and Stage B new HF, respectively. Stage B new was further evaluated as elevated biomarker only, abnormal echocardiogram only, and abnormalities in both (echo + biomarker). The authors assessed risk for incident HF and all-cause death using Cox regression., Results: Overall, 4,326 (81.3%) individuals were classified as Stage B new with 1,123 (21.1%) meeting criteria for elevated biomarkers only. Compared with Stage A new , Stage B new was associated with increased risk for incident HF (HR: 3.70 [95% CI: 2.58-5.30]) and death (HR: 1.94 [95% CI: 1.53-2.46]). Stage B biomarkers only and Stage B echo only were associated with increased HF risk, whereas Stage B biomarkers only was also associated with increased death. Stage B echo+biomarker had the highest risk for HF (HR: 6.34 [95% CI: 4.37-9.19]) and death (HR: 2.53 [95% CI: 1.98-3.23])., Conclusions: Incorporating biomarkers based on the new HF guideline reclassified approximately 1 in 5 older adults without prevalent HF to Stage B. The routine measurement of biomarkers can help to identify individuals at higher HF risk who may benefit most from HF prevention efforts., Competing Interests: Funding Support and Author Disclosures The ARIC study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract numbers (75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, 75N92022D00005). Dr Bozkurt has received consulting fees from Bristol Myers Squibb, scPharmaceuticals, Baxter Healthcare Corporation, Sanofi-Aventis, Relypsa, Amgen; serves on the Clinical Event Committee for GUIDE HF Trial sponsored by Abbott Vascular, and Data Safety Monitoring Committee of ANTHEM trial (Autonomic REGULATION Therapy to Enhance Myocardial Function and Reduce progression of Heart Failure with reduced ejection fraction) sponsored by Liva Nova. Dr Ballantyne has received research support from National Institutes of Health grant R01HL134320 (relevant to study), Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Novartis, Regeneron, Roche Diagnostic, National Institutes of Health, AHA, and ADA; is a consultant for Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Matinas BioPharma Inc, Merck–New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo. Dr Hoogeveen has received research grants from Denka Seiken and serves as a consultant to Denka Seiken. Dr de Lemos has received grant support from Abbott Diagnostics and Roche Diagnostics; and consulting income from Siemen’s Health Care Diagnostics, Quidel, Beckman Coulter, and Ortho Clinical Diagnostics; and is the co-inventor on a patent awarded to University of Maryland using high sensitivity cardiac troponin T and left ventricular hypertrophy as markers of heart failure risk (patent number: 61990386). Dr Nambi has stock ownership in Abbott labs. Dr Shah has received research support from Novartis and Philips Ultrasound; and consulting fees from Philips Ultrasound and Janssen. Dr Selvin has received research funding support from the National Institutes of Health grant R01HL134320 (relevant to study). Dr Virani has received grant support from the U.S. Department of Veterans Affairs, National Institutes of Health, Tahir, and the Jooma Family; and has received honorarium from the American College of Cardiology (Associate Editor for Innovations, acc.org). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Rationale & Objective: Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individuals with CKD to understand the patterns and trajectories of HF-type symptoms in this setting., Study Design: Prospective cohort study., Setting & Participants: 3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF., Predictors: Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and electrocardiographic parameters., Outcome: Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire [KCCQ] Overall Summary Score with a range of 0-100 where<75 reflects clinically significant symptoms)., Analytical Approach: Latent class mixed models were used to model trajectories. Multinomial logistic regression was used to model relationships of predictors with trajectory group membership., Results: Five trajectories of KCCQ score were identified in the cohort of 3,044 adults, 45% of whom were female, and whose median age was 61 years. Group 1 (41.7%) had a stable high score (minimal symptoms, average score of 96); groups 2 (35.6%) and 3 (15.6%) had stable but lower scores (mild symptoms [average of 81] and clinically significant symptoms [average of 52], respectively). Group 4 (4.9%) had a substantial worsening in symptoms over time (mean 31-point decline), and group 5 (2.2%) had a substantial improvement (mean 33-point increase) in KCCQ score. A majority of group 1 was male, without diabetes or obesity, and this group had higher baseline kidney function. A majority of groups 2 and 3 had diabetes and obesity. A majority of group 4 was male and had substantial proteinuria. Group 5 had the highest proportion of baseline cardiovascular disease (CVD)., Limitations: No validation cohort available, CKD management changes in recent years may alter trajectories, and latent class models depend on the missing at random assumption., Conclusions: Distinct HF-type symptom burden trajectories were identified in the setting of CKD, corresponding to different baseline characteristics. These results highlight the diversity of HF-type symptom experiences in individuals with CKD., (Copyright © 2022 National Kidney Foundation, Inc. All rights reserved.)

Importance: Most studies, especially in primary prevention patients, have evaluated N-terminal B-type natriuretic peptide (NT-proBNP) at one time point. Evaluation of change in NT-proBNP may improve risk stratification for incident cardiovascular events., Objective: To assess the association between change in NT-proBNP and risk for incident heart failure (HF) and death., Design, Setting, and Participants: Participants were recruited from 4 US communities enrolled in the Atherosclerosis Risk in Community (ARIC) study. Individuals who attended ARIC visits 2 and 4 (approximately 6 years apart) with measurements of NT-proBNP and without prevalent HF were included. Assays of NT-proBNP were conducted between 2011 and 2013, and analysis took place between July 2021 and October 2022., Exposures: The primary exposure variable was NT-proBNP change between visits 2 and 4, modeled as change categories (<125 pg/mL or ≥125 pg/mL) and as percent change., Main Outcomes and Measures: The primary outcome measures were incident HF hospitalization and all-cause death. The association between changes in cardiovascular risk factors with change in NT-proBNP was further assessed., Results: A total of 9776 individuals (mean [SD] age, 57.1 [5.7] years at visit 2; 5523 [56.5%] women) were included in the study. Compared with participants with NT-proBNP level less than 125 pg/mL at both visits, participants with NT-proBNP level of 125 pg/mL or higher at both visits had an increase in incident HF (adjusted hazard ratio [HR], 2.40 [95% CI, 2.00-2.88]) and mortality risk (HR, 1.68 [95% CI, 1.47-1.91). Participants with NT-proBNP levels of 125 pg/mL or higher at visit 2 and less than 125 pg/mL at visit 4 had similar risk for HF and death (HR, 1.01 [95% CI, 0.71-1.43]; HR, 0.79 [95% CI, 0.61-1.01]) compared with the group with NT-proBNP levels of less than 125 pg/mL at both visits. The percent change in NT-proBNP was positively associated with HF and death (HR, 1.06 [95% CI, 1.02-1.10]; HR, 1.05 [95% CI, 1.03-1.08] per 1-SD increase, respectively). Change in systolic blood pressure, low-density lipoprotein cholesterol, triglyceride level, body mass index, and estimated glomerular filtration rate were significantly associated with change in NT-proBNP., Conclusions and Relevance: In this study, 6-year change in NT-proBNP reflected dynamic change in risk for HF events and death among community-dwelling adults without prevalent clinical HF. These results support the utility of serial NT-proBNP measurements to improve risk stratification of patients with pre-HF.

Background Computational fluid dynamics has shown good agreement with contrast-enhanced magnetic resonance imaging measurements in cardiovascular disease applications. We have developed a biomechanical model of microvascular perfusion using contrast-enhanced magnetic resonance imaging signal intensities derived from skeletal calf muscles to study peripheral artery disease (PAD). Methods and Results The computational microvascular model was used to study skeletal calf muscle perfusion in 56 individuals (36 patients with PAD, 20 matched controls). The recruited participants underwent contrast-enhanced magnetic resonance imaging and ankle-brachial index testing at rest and after 6-minute treadmill walking. We have determined associations of microvascular model parameters including the transfer rate constant, a measure of vascular leakiness; the interstitial permeability to fluid flow which reflects the permeability of the microvasculature; porosity, a measure of the fraction of the extracellular space; the outflow filtration coefficient; and the microvascular pressure with known markers of patients with PAD. Transfer rate constant, interstitial permeability to fluid flow, and microvascular pressure were higher, whereas porosity and outflow filtration coefficient were lower in patients with PAD than those in matched controls (all P values ≤0.014). In pooled analyses of all participants, the model parameters (transfer rate constant, interstitial permeability to fluid flow, porosity, outflow filtration coefficient, microvascular pressure) were significantly associated with the resting and exercise ankle-brachial indexes, claudication onset time, and peak walking time (all P values ≤0.013). Among patients with PAD, interstitial permeability to fluid flow, and microvascular pressure were higher, while porosity and outflow filtration coefficient were lower in treadmill noncompleters compared with treadmill completers (all P values ≤0.001). Conclusions Computational microvascular model parameters differed significantly between patients with PAD and matched controls. Thus, computational microvascular modeling could be of interest in studying lower extremity ischemia.

Background: Given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong associations observed between hypertension and its sequelae on hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, we hypothesized that intensive systolic blood pressure (SBP) lowering would decrease levels of hs-cTnT and NT-proBNP., Methods: hs-cTnT and NT-proBNP were measured at baseline and 1 year from stored specimens in SPRINT (Systolic Blood Pressure Intervention Trial). Changes in biomarkers were evaluated continuously on the log scale and according to categories (≥50% increase, ≥50% decrease, or <50% change). The effect of intensive SBP lowering on continuous and categorical changes in biomarker levels were assessed using linear and multinomial logistic regression models, respectively. The association between changes in biomarkers on heart failure and death was assessed using multivariable-adjusted Cox proportional hazards models., Results: Randomization to intensive SBP lowering (versus standard SBP management) resulted in a 3% increase in hs-cTnT levels over 1-year follow-up (geometric mean ratio, 1.03 [95% CI, 1.01-1.04]) and a higher proportion of participants with ≥50% increase (odds ratio, 1.47 [95% CI, 1.13, 1.90]). In contrast, randomization to intensive SBP lowering led to a 10% decrease in NT-proBNP (geometric mean ratio, 0.90 [95% CI, 0.87-0.93]) and a lower probability of ≥50% increase in NT-proBNP (odds ratio, 0.57 [95% CI, 0.46-0.72]). The association of randomized treatment assignment on change in hs-cTnT was completely attenuated after accounting for changes in estimated glomerular filtration rate over follow-up, whereas the association of treatment with NT-proBNP was completely attenuated after adjusting for change in SBP. Increases in hs-cTnT and NT-proBNP from baseline to 1 year were associated with higher risk for heart failure and death, with no significant interactions by treatment assignment., Conclusions: Intensive SBP lowering increased hs-cTnT, mediated by the effect of SBP lowering on reduced kidney filtration. In contrast, intensive SBP lowering decreased NT-proBNP, a finding that was explained by the decrease in SBP. These findings highlight the importance of noncardiac factors influencing variation in cardiac biomarkers and raise questions about the potential role of hs-cTnT as a surrogate marker for heart failure or death in SBP-lowering studies.

Background: Severe hypertriglyceridemia is often caused by variants in genes of triglyceride metabolism. These variants include rare, heterozygous pathogenic variants (PVs), or multiple common, small-effect single nucleotide polymorphisms that can be quantified using a polygenic risk score (PRS). The role of genetic testing to examine PVs and PRS in predicting risk for pancreatitis and severity of hypertriglyceridemia is unknown., Methods: We examined the relationship of PVs and PRSs associated with hypertriglyceridemia with the highest recorded plasma triglyceride level and risk for acute pancreatitis in 363 patients from 3 academic lipid clinics who underwent genetic testing (GBinsight's Dyslipidemia Comprehensive Panel). Categories of hypertriglyceridemia included: normal triglyceride (<200 mg/dL), moderate (200-499 mg/dL), severe (500-999 mg/dL), or very severe (≥1000 mg/dL)., Results: PVs and high PRSs were identified in 37 (10%) and 59 (16%) individuals, respectively. Patients with both had increased risk for very severe hypertriglyceridemia compared with those with neither genetic risk factor. Risk for acute pancreatitis was also increased in individuals with both genetic risk factors (odds ratio, 5.1 [ P =0.02] after controlling for age, race, sex, body mass index, and highest triglyceride level), but not in individuals with PV or high PRS alone., Conclusions: The presence of both PV and high PRS significantly increased risk for very severe hypertriglyceridemia and acute pancreatitis, whereas PV or PRS alone only modestly increased risk. Genetic testing may help identify patients with hypertriglyceridemia who have the greatest risk for developing pancreatitis and may derive the greatest benefit from novel triglyceride-lowering therapies.

Background Plasma lipoprotein(a) (Lp[a]) concentrations are primarily determined by genetic factors and are believed to remain stable throughout life. However, data are scarce on longitudinal trends in Lp(a) concentrations over time. Therefore, it is unclear whether measurement of Lp(a) once in a person's life is sufficient for cardiovascular risk assessment in all adults. Methods and Results Lp(a) concentrations, specifically apolipoprotein(a) concentrations, were measured at visits 4 and 5, ≈15 years apart, in 4734 adult participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age at visits 4 and 5, 60.7±5.1 and 75.5±5.2 years, respectively). Participants were categorized by baseline (visit 4) Lp(a) concentrations as normal (<30 mg/dL), borderline-high (30-49 mg/dL), or high (≥50 mg/dL). We compared adults with Lp(a) change ≥20 mg/dL between visits and those with Lp(a) change <20 mg/dL. Multivariable logistic regression analysis was used to identify covariates associated with change in Lp(a) over time. At visit 5, 58.1% of participants with borderline-high Lp(a) concentrations of 30 to 49 mg/dL at visit 4 had high Lp(a) concentrations ≥50 mg/dL. Participants with low Lp(a) (<30 mg/dL) or high Lp(a) (≥50 mg/dL) at visit 4 tended to stay in these respective categories. Black race, female sex, diabetes, hypertension, total cholesterol, and albuminuria were associated with significantly greater probability for Lp(a) change ≥20 mg/dL over time. Conclusions Our results suggest that adults with borderline-high Lp(a) concentrations may be considered for repeat monitoring of Lp(a) over time, particularly if they are Black, women, or have diabetes, hypertension, and/or elevated albuminuria.

Peripheral artery disease (PAD) causes lower extremity dysfunction and is associated with an increased risk of cardiovascular mortality and morbidity. In this study, we analyzed how non-invasive 2-dimensional-phase-contrast magnetic resonance imaging (2D-PC-MRI) measured velocity markers of the distal superficial femoral artery (SFA) are associated with clinical and functional characteristics of PAD. A total of 70 (27 diabetic and 43 non-diabetic) PAD patients were included in this secondary analysis of data collected from the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Electrocardiographically (ECG)-gated 2D-PC-MRI was performed at a proximal and a distal imaging location of the distal SFA. Baseline characteristics did not differ between diabetic and non-diabetic PAD patients. Claudication onset time (COT) was shorter in diabetic PAD patients compared to non-diabetics (0.56 (inter quartile range (IQR): 0.3, 2.04) minutes vs. 1.30 (IQR: 1.13, 2.15) minutes, p = 0.025). In a pooled analysis of all 70 PAD patients, maximum velocity was significantly higher in the proximal compared with the distal SFA segment (43.97 (interquartile range (IQR): 20.4, 65.2) cm/s; vs. 34.9 (IQR: 16.87, 51.71) cm/s; p < 0.001). The maximum velocities in both the proximal and distal SFA segments were significantly higher in diabetic PAD patients compared with non-diabetics (proximal: 53.6 (IQR: 38.73, 89.43) cm/s vs. 41.49 (IQR: 60.75, 15.9) cm/s, p = 0.033; distal: 40.8 (IQR: 23.7, 71.90) cm/s vs. 27.4 (IQR: 41.67, 12.54) cm/s, p = 0.012). Intra-observer variability, as assessed by intraclass correlation (ICC) analysis, was excellent for SFA mean and maximum velocities (0.996 (confidence interval [CI]: 0.996, 0.997); 0.999 (CI: 0.999, 0.999)). In conclusion, 2D-PC-MRI SFA velocity measures are reproducible and may be of interest in assessing diabetic and non-diabetic PAD patients., Competing Interests: Declaration of Competing Interest Gerd Brunner reports financial support was provided by National Institutes of Health. Gerd Brunner reports financial support was provided by American Heart Association., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The United States Preventive Services Taskforce (USPSTF) recently released recommendations for statin therapy eligibility for the primary prevention of cardiovascular disease (CVD). We report the proportion and the absolute number of US adults who would be eligible for statin therapy under these recommendations and compare them with the previously published 2018 American Heart Association (AHA)/ American College of Cardiology (ACC)/ Multisociety (MS) Cholesterol guidelines., Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 of adults aged 40-75 years without prevalent self-reported atherosclerotic CVD (ASCVD) and low-density lipoprotein-cholesterol <190 mg/dL. The 2022 USPSTF recommends statin therapy for primary prevention in those with a 10-year ASCVD risk of ≥10% and ≥ 1 CVD risk factor (diabetes mellitus, dyslipidemia, hypertension, or smoking). The 2018 AHA/ ACC/ MS Cholesterol guideline recommends considering statin therapy for primary prevention for those with diabetes mellitus, or 10-year ASCVD risk ≥20% or 10-year ASCVD risk 7.5 to <20% after accounting for risk-enhancers and shared decision making. Survey recommended weights were used to project these proportions to national estimates., Results: Among 1799 participants eligible for this study, the weighted mean age was 56.0 ± 0.5 years, with 53.0% women (95% confidence interval [CI] 49.7, 56.3), and 10.6% self-reported NH Black individuals (95% CI 7.7, 14.3). The weighted mean 10-year ASCVD risk was 9.6 ± 0.3%. The 2022 USPSTF recommendations and the 2018 AHA/ ACC/ MS Cholesterol guidelines indicated eligibility for statin therapy in 31.8% (95% CI 28.6, 35.1) and 46.8% (95% CI 43.0, 50.5) adults, respectively. These represent 33.7 million (95% CI 30.4, 37.2) and 49.7 million (95% CI 45.7, 53.7) adults, respectively. For those with diabetes mellitus, 2022 USPSTF recommended statin therapy in 63.0% (95% CI 52.1, 72.7) adults as compared with all adults with diabetes aged 40-75 years under the 2018 AHA/ ACC/ MS Cholesterol guidelines., Conclusion: In this analysis of the nationally representative US population from 2017 to 2020, approximately 15% (~16.0 million) fewer adults were eligible for statin therapy for primary prevention under the 2022 USPSTF recommendations as compared to the 2018 AHA/ ACC/ MS Cholesterol guideline., Competing Interests: Declaration of Competing Interest VB: Through contracts between UAB and the sponsor, VB was national coordinator for the STRENGTH Trial (Astra Zeneca) and the Dalgene trial (DalCor); is national coordinator for the CLEAR Outcomes trial (Esperion) and Steering Committee member for the ODYSSEY OUTCOMES trial (Sanofi/Regeneron) and serves as site PI for the ORION trial (Novartis). She was a consultant for Pfizer and currently serves on a Data Safety and Monitoring Board for Verve Therapeutics. LS: consulting honoraria from Amgen and Regeneron. NJS: honorarium for an educational presentation from Knowledge to Practice. This company has no ties to industry. CJL: Consultant and Speaker for Amgen and Sanofi on their PCSK9Is and for Novartis on their new injectable and speaker and consultant for DSM and GOED on omega-3, speaker and Consultant for Esperion., (Published by Elsevier Inc.)

Background: Left ventricular hypertrophy (LVH) combined with elevations in cardiac biomarkers reflecting myocardial injury and neurohormonal stress (malignant LVH) is associated with a high risk for heart failure and death., Objectives: The aim of this study was to determine the impact of intensive systolic blood pressure (SBP) control on the prevention of malignant LVH and its consequences., Methods: A total of 8,820 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were classified into groups based on the presence or absence of LVH assessed by 12-lead ECG, and elevations in biomarker levels (high-sensitivity cardiac troponin T ≥14 ng/L or N-terminal pro-B-type natriuretic peptide ≥125 pg/mL) at baseline. The effects of intensive vs standard SBP lowering on rates of acute decompensated heart failure (ADHF) events and death and on the incidence and regression of malignant LVH were determined., Results: Randomization to intensive SBP lowering led to similar relative reductions in ADHF events and death across the combined LVH/biomarker groups (P for interaction = 0.68). The absolute risk reduction over 4 years in ADHF events and death was 4.4% (95% CI: -5.2% to 13.9%) among participants with baseline malignant LVH (n = 449) and 1.2% (95% CI: 0.0%-2.5%) for those without LVH and nonelevated biomarkers (n = 4,361). Intensive SBP lowering also reduced the incidence of malignant LVH over 2 years (2.5% vs 1.1%; OR: 0.44; 95% CI: 0.30-0.63)., Conclusions: Intensive SBP lowering prevented malignant LVH and may provide substantial absolute risk reduction in the composite of ADHF events and death among SPRINT participants with baseline malignant LVH., Competing Interests: Funding Support and Author Disclosures This ancillary study was supported by the National Heart, Lung, and Blood Institute (1R01HL144112-01 for Dr Berry). Analytical reagents for hs-cTnT and NT-proBNP measurements were donated by Roche. SPRINT was sponsored by the National Institutes of Health, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under Contract Numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, HHSN268200900049C, and Inter-Agency Agreement Number A-HL-13–002-001. It was also supported in part with resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the U.S. Department of Veterans Affairs, or the United States Government. Support was also received from the following CTSAs funded by the National Center for Advancing Translational Sciences: CWRU: UL1TR000439, OSU: UL1RR025755, U Penn: UL1RR024134 and UL1TR000003, Boston: UL1RR025771, Stanford: UL1TR000093, Tufts: UL1RR025752, UL1TR000073 and UL1TR001064, University of Illinois: UL1TR000050, University of Pittsburgh: UL1TR000005, UT Southwestern: 9U54TR000017–06, University of Utah: UL1TR000105–05, Vanderbilt University: UL1 TR000445, George Washington University: UL1TR000075, University of California, Davis: UL1 TR000002, University of Florida: UL1 TR000064, University of Michigan: UL1TR000433, Tulane University: P30GM103337 COBRE Award NIGMS, Wake Forest University: UL1TR001420. Dr de Lemos has received grant support from Roche Diagnostics and Abbott Diagnostics; has received consulting fees from Roche Diagnostics, Abbott Diagnostics, Ortho Clinical Diagnostics, Quidel Cardiovascular, Inc, and Siemen’s Health Care Diagnostics; and has been named a co-owner on a patent awarded to the University of Maryland (US Patent Application Number: 15/309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure.” Dr Kitzman has received honoraria as a consultant outside the present study from Bayer, Merck, Pfizer, Corvia Medical, Boehringer Ingelheim, Ketyo, Rivus, Novo Nordisk, AstraZeneca, and Novartis; has received grant funding from Novartis, Bayer, Pfizer, Novo Nordisk, and AstraZeneca; and has stock ownership in Gilead Sciences. Dr Berry has received grant support from the National Institutes of Health, Roche Diagnostics, and Abbott Diagnostics; and has received consulting fees from Roche Diagnostics and the Cooper Institute. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The aim of this secondary analysis of ELIMIT (The Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial) was to determine longitudinal changes over 24 months in skeletal thigh muscle volumes and individual muscle compartments in patients with peripheral artery disease (PAD) with and without diabetes. A total of 48 patients with available magnetic resonance imaging of the distal superficial femoral artery at baseline and 2 years were included in this analysis. Muscle volumes and superficial femoral artery wall, lumen, and total vessel volumes were quantified. Intrareader reproducibility of muscle tracings was assessed with the intraclass correlation coefficient using a 2-way model. Baseline characteristics were similar between patients with PAD with and without diabetes, except for smoking history (p = 0.049), cholesterol levels (p <0.050), and calf walking pain (p = 0.049). Interobserver reproducibility of the muscle volume tracings was excellent for all muscle groups (all intraclass correlation coefficients >0.86, confidence interval 0.69 to 0.94). Total muscle and total leg volumes increased significantly between baseline and 24 months among patients with PAD without diabetes (31 ± 6.4 cm 3 vs 32 ± 7.0 cm 3 , p <0.001; 18 ± 4.4 cm 3 vs 19 ± 4.8 cm 3 , p = 0.045), whereas there was no change in patients with PAD and diabetes. Total muscle volume was inversely associated with age and body mass index in patients with PAD both with and without diabetes (p <0.05). In conclusion, magnetic resonance imaging-quantified thigh muscle volumes are highly reproducible and may be of interest in assessing PAD patients with and without diabetes., Competing Interests: Disclosures Dr. Virani declares grant support from the Department of Veterans Affairs, NIH, the Tahir and Jooma Family, and an honorarium from the American College of Cardiology (Associate Editor for Innovations, acc.org). The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Diabetes exerts adverse effects on the heart, and a longer diabetes duration is associated with greater heart failure risk. We studied diabetes duration and subclinical myocardial injury, as reflected by high-sensitivity cardiac troponin (hs-cTnT)., Methods: We analyzed 9052 participants without heart failure or coronary heart disease (mean age 63 years, 58% female, 21% Black, 15% with diabetes) at The Atherosclerosis Risk in Communities Study (ARIC) Visit 4 (1996 to 1998). Diabetes duration was calculated based on diabetes status at Visits 1 (1987 to 1989) through 4, or using self-reported age of diabetes diagnosis prior to Visit 1. We used multinomial logistic regression to determine the association of diabetes duration with increased (≥14 ng/L) or detectable (≥6 ng/L) Visit 4 hs-cTnT, relative to undetectable hs-cTnT, adjusted for demographics and cardiovascular risk factors., Results: The prevalence of increased Visit 4 hs-cTnT was higher in persons with longer diabetes duration, from 12% for those with diabetes 0 to <5 years up to 31% among those with diabetes for ≥15 years (P for trend <0.0001). New onset diabetes at Visit 4 was associated with 1.92× higher relative risk (95% CI, 1.27-2.91) of increased hs-cTnT than no diabetes. Longer diabetes duration was associated with greater myocardial injury, with duration ≥15 years associated with 9.29× higher risk (95% CI, 5.65-15.29) for increased hs-cTnT and 2.07× (95% CI, 1.24-3.16) for detectable hs-cTnT, compared to no diabetes., Conclusions: Longer diabetes duration is strongly associated with subclinical myocardial injury. Interventional studies are needed to assess whether the prevention and delay of diabetes onset can mitigate early myocardial damage., (© American Association for Clinical Chemistry 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This analysis sought to determine factors (including adiposity-related factors) most associated with HF-type symptoms (fatigue, shortness of breath, and edema) in adults with chronic kidney disease (CKD)., Background: Symptom burden impairs quality of life in CKD, especially symptoms that overlap with HF. These symptoms are common regardless of clinical HF diagnosis, and may be affected by subtle cardiac dysfunction, kidney dysfunction, and other factors. We used machine learning to investigate cross-sectional relationships of clinical variables with symptom scores in a CKD cohort., Methods: Participants in the Chronic Renal Insufficiency Cohort (CRIC) with a baseline modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score were included, regardless of prior HF diagnosis. The primary outcome was Overall Summary Score as a continuous measure. Predictors were 99 clinical variables representing demographic, cardiac, kidney and other health dimensions. A correlation filter was applied. Random forest regression models were fitted. Variable importance scores and adjusted predicted outcomes are presented., Results: The cohort included 3426 individuals, 10.3% with prior HF diagnosis. BMI was the most important factor, with BMI 24.3 kg/m 2 associated with the least symptoms. Symptoms worsened with higher or lower BMIs, with a potentially clinically relevant 5 point score decline at 35.7 kg/m 2 and a 1-point decline at the threshold for low BMI, 18.5 kg/m 2 . The most important cardiac and kidney factors were heart rate and eGFR, the 4th and 5th most important variables, respectively. Results were similar for secondary analyses., Conclusions: In a CKD cohort, BMI was the most important feature for explaining HF-type symptoms regardless of clinical HF diagnosis, identifying an important focus for symptom directed investigations., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Adequate physical activity is an integral requirement for achieving cardiovascular health. Physical inactivity is the fourth leading cause of death worldwide. Hence, it is important to identify racial/ethnic groups that are less likely to achieve sufficient physical activity levels, and to address barriers to meeting physical activity requirements., Methods: Cross-sectional data from the 2006-2015 National Health Interview Survey (NHIS) were used to compare self-reported sufficient physical activity among different racial/ethnic groups: non-Hispanic (NH) Whites, NH Blacks, NH Asians, and Hispanics in the United States. Sufficient physical activity was defined as ≥ 150 minutes per week of moderate-intensity physical activity, ≥ 75 minutes per week of vigorous-intensity physical activity, or ≥ 150 minutes per week of moderate and vigorous physical activity., Results: The study sample consisted of 296,802 individuals, mean age ± standard error age 46.4 ± 0.10 years, 52% women, 70% NH White, 12% NH Black, 5% NH Asian, and 14% Hispanic. The prevalence of sufficient physical activity in the overall population was 46%, while it was 48% among NH Whites, 39% among NH Blacks, 45% among NH Asians, and 40% among Hispanics. In multivariable-adjusted models (odds ratio; 95% confidence interval), NH Blacks (0.79; 0.64,0.97), NH Asians (0.72; 0.62,0.85) and Hispanics (0.71; 0.61,0.82) were significantly less likely to engage in sufficient physical activity compared with NH Whites. Older age, women, and low income were inversely associated with sufficient physical activity, while a college education or higher was associated directly with it., Conclusions: NH Black and Asian Americans and Hispanic adults were less likely to engage in sufficient physical activity levels compared with Whites. It is important to address barriers to meeting physical activity thresholds to help achieve optimal cardiovascular health., (© 2022 The University of Kansas Medical Center.)

Septic shock is a life-threatening host response to infection and a significant contributor to cost burden in the United States. Furthermore, sepsis-related inflammation has been linked to myocardial infarction (MI). We sought to examine the association of type 1 and type 2 MI with outcomes in hospitalizations admitted with septic shock. The National Readmission Database 2018 was queried to identify hospitalizations with hospital discharge diagnoses of septic shock without MI, septic shock with type 1 MI, or septic shock with type 2 MI. Complex-sample multivariable logistic and linear regression models were used to determine the association of these conditions with clinical outcomes. Of 354,528 hospitalizations with septic shock, 11,519 had type 1 MI (3.2%) and 13,970 had type 2 MI (3.9%). Compared with septic shock without MI, type 1 MI was associated with higher mortality (adjusted odds ratio [OR] 1.67, 95% confidence interval [CI] 1.57 to 1.77), costs (adjusted parameter estimate $4,571, 95% CI 3,020 to 6,122), and discharge to facility (adjusted OR 1.09, 95% CI 1.01 to 1.17). In contrast, septic shock with type 2 MI was associated with similar mortality and discharge to nursing facility and higher costs (adjusted parameter estimate 1,798, 95% CI 549 to 3,047). Septic shock hospitalizations with type 1 MI had higher in-hospital mortality (adjusted OR 1.74, 95% CI 1.60 to 1.90, p <0.001) compared with type 2 MI. In conclusion, type 1 MI is associated with higher mortality and resource utilization among septic shock hospitalizations. Furthermore, type 2 MI was associated with higher resource utilization., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022. Published by Elsevier Inc.)

A large interarm difference in brachial systolic blood pressure (SBP) (≥10 or ≥15 mmHg) is strongly associated with elevated cardiovascular events and mortality. Evidence demonstrating whether such contralateral differences in SBP occur in ankle blood pressure and its association with arterial stiffness is scarce. The aims of this study were to characterize arm and ankle contralateral SBP differences in a sample of community-dwelling older adults (5077), and to determine whether this difference is associated with arterial stiffness assessed by pulse wave velocity (PWV) between the heart and ankle (haPWV), femoral artery and ankle (faPWV), and brachial artery and ankle (baPWV) in the right and left sides. Prevalence of interarm SBP differences ≥10 and ≥15 mmHg was 5.1% and .7%, respectively; the corresponding prevalence for interankle SBP was 24.9% and 12.0%. Higher BMI and lower ankle-brachial index (ABI) were significantly correlated with greater interarm SBP differences. Increased age, higher BMI, lower ABI, and greater contralateral differences in haPWV, faPWV, and baPWV were significantly correlated to greater interankle SBP differences. Interankle SBP difference ≥15 mmHg was significantly associated with contralateral differences of >80 cm/s in haPWV (OR = 1.94 [95% CI = 1.52-2.49]), >165 cm/s in faPWV (OR = 1.64 [95% CI = 1.27-2.12]), and >240 cm/s in baPWV (OR = 2.43 [95% CI = 1.94-3.05]). The associations remained significant after adjustment for age, sex, race, BMI, smoking status, and ABI. Compared with interarm differences, interankle differences in SBP are common in older adults. The magnitude of interankle, but not interarm, differences in SBP is associated with various measures of arterial stiffness., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)