Obesity and related cardiometabolic traits including insulin resistance are more strongly associated with risk of future HFpEF versus HFrEF. The differential risk of HFpEF with obesity seems particularly pronounced among women and may underlie sex differences in HF subtypes.

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Background Procoagulant platelets are a subset of highly activated platelets with a critical role in thrombin generation. Evaluation of their clinical utility in thrombotic disorders, such as coronary artery disease (CAD), has been thwarted by the lack of a sensitive and specific whole blood assay. Objectives We developed a novel assay, utilizing the cell death marker, GSAO [(4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid], and the platelet activation marker, P-selectin, to identify procoagulant platelets in whole blood by flow cytometry. Patients/Methods Using this assay, we characterized the procoagulant platelet population in healthy controls and a cohort of patients undergoing elective coronary angiography. Results In patients with CAD, compared with patients without CAD, there was a heightened procoagulant platelet response to thrombin (25.2% vs. 12.2%), adenosine diphosphate (ADP) (7.8% vs. 2.7%) and thrombin plus collagen (27.2% vs. 18.3%). The heightened procoagulant platelet potential in CAD patients was not associated with other markers of platelet function, including aggregation, dense granule release and activation of α β integrin. Although dual antiplatelet therapy (DAPT) was associated with partial suppression of procoagulant platelets, this inhibitory effect on a patient level could not be predicted by aggregation response to ADP and was not fully suppressed by clopidogrel. Conclusions We report for the first time that procoagulant platelets can be efficiently detected in a few microliters of whole blood using the cell death marker, GSAO, and the platelet activation marker, P-selectin. A heightened procoagulant platelet response may provide insight into the thrombotic risk of CAD and help identify a novel target for antiplatelet therapies in CAD.

OBJECTIVES The aim of this study was to assess the odds of initiation or continuation of pharmacological and lifestyle preventive therapies in patients with nonzero versus zero coronary artery calcium (CAC) score detected on cardiac computed tomography. BACKGROUND Detection of calcified coronary plaque could serve as a motivational tool for physicians and patients to intensify preventive therapies. METHODS We searched PubMed, EMBASE (Excerpta Medica database), Web of Science, Cochrane CENTRAL (Cochrane central register of controlled trials), ClinicalTrials.gov, and the International Clinical Trials Registry Platform for studies evaluating the association of CAC scores with downstream pharmacological or lifestyle interventions for prevention of cardiovascular disease. Pooled odds ratios (ORs) of downstream interventions were obtained using the DerSimonian and Laird random effects model. RESULTS After a review of 6,256 citations and 54 full-text papers, 6 studies (11,256 participants, mean follow-up time: 1.6 to 6.0 years) were included. Pooled estimates of the odds of aspirin initiation (OR: 2.6; 95% confidence interval [CI]: 1.8 to 3.8), lipid-lowering medication initiation (OR: 2.9; 95% CI: 1.9 to 4.4), blood pressure–lowering medication initiation (OR: 1.9; 95% CI: 1.6 to 2.3), lipid-lowering medication continuation (OR: 2.3; 95% CI: 1.6 to 3.3), increase in exercise (OR: 1.8; 95% CI: 1.4 to 2.4), and dietary change (OR: 1.9; 95% CI: 1.5 to 2.5) were higher in individuals with nonzero CAC versus zero CAC scores, but not for aspirin or blood pressure–lowering medication continuation. When assessed within individual studies, these findings remained significant after adjustment for baseline patient characteristics and cardiovascular risk factors. CONCLUSIONS This systematic review and meta-analysis suggests that nonzero CAC score, identifying calcified coronary plaque, significantly increases the likelihood of initiation or continuation of pharmacological and lifestyle therapies for the prevention of cardiovascular disease. (J Am Coll Cardiol Img 2017;10:833–42)

Background Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear. Objectives The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF. Methods The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio. Results Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p < 0.001), and the combined clinical model had good discrimination in men (C-statistic = 0.80) and in women (C-statistic = 0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic = 0.006; likelihood ratio chi-square = 146; p < 0.001), and after adding cardiac troponins in women (ΔC-statistic = 0.003; likelihood ratio chi-square = 73; p < 0.001). Conclusions CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in a clinical HF risk prediction model is limited in both sexes.

Objective To assess age differences in risk factors for incident heart failure in the general population. Design Pooled population based cohort study. Setting Framingham Heart Study, Prevention of Renal and Vascular End-stage Disease Study, and Multi-Ethnic Study of Atherosclerosis. Participants 24 675 participants without a history of heart failure stratified by age into young (<55 years; n=11 599), middle aged (55-64 years; n=5587), old (65-74 years; n=5190), and elderly (≥75 years; n=2299) individuals. Main outcome measure Incident heart failure. Results Over a median follow-up of 12.7 years, 138/11 599 (1%), 293/5587 (5%), 538/5190 (10%), and 412/2299 (18%) of young, middle aged, old, and elderly participants, respectively, developed heart failure. In young participants, 32% (n=44) of heart failure cases were classified as heart failure with preserved ejection fraction compared with 43% (n=179) in elderly participants. Risk factors including hypertension, diabetes, current smoking history, and previous myocardial infarction conferred greater relative risk in younger compared with older participants (P for interaction <0.05 for all). For example, hypertension was associated with a threefold increase in risk of future heart failure in young participants (hazard ratio 3.02, 95% confidence interval 2.10 to 4.34; P<0.001) compared with a 1.4-fold risk in elderly participants (1.43, 1.13 to 1.81; P=0.003). The absolute risk for developing heart failure was lower in younger than in older participants with and without risk factors. Importantly, known risk factors explained a greater proportion of overall population attributable risk for heart failure in young participants (75% v 53% in elderly participants), with better model performance (C index 0.79 v 0.64). Similarly, the population attributable risks of obesity (21% v 13%), hypertension (35% v 23%), diabetes (14% v 7%), and current smoking (32% v 1%) were higher in young compared with elderly participants. Conclusions Despite a lower incidence and absolute risk of heart failure among younger compared with older people, the stronger association and greater attributable risk of modifiable risk factors among young participants highlight the importance of preventive efforts across the adult life course.

When performed at the time of outpatient echocardiography, LUS findings of pulmonary congestion differ between patients with known HF and those with hypertension, and may be associated with adverse outcomes.

Background Men are at higher risk for serious complications related to COVID-19 infection than women. More robust immune activation in women has been proposed to contribute to decreased disease severity, although systemic inflammation has been associated with worse outcomes in COVID-19 infection. Whether systemic inflammation contributes to sex differences in COVID-19 infection is not known. Study design and methods We examined sex differences in inflammatory markers among 453 men (mean age 61) and 328 women (mean age 62) hospitalized with COVID-19 infection at the Massachusetts General Hospital from March 8 to April 27, 2020. Multivariable linear regression models were used to examine the association of sex with initial and peak inflammatory markers. Exploratory analyses examined the association of sex and inflammatory markers with 28-day clinical outcomes using multivariable logistic regression. Results Initial and peak CRP were higher in men compared with women after adjustment for baseline differences (initial CRP: ß 0.29, SE 0.07, p = 0.0001; peak CRP: ß 0.31, SE 0.07, p<0.0001) with similar findings for IL-6, PCT, and ferritin (p<0.05 for all). Men had greater than 1.5-greater odds of dying compared with women (OR 1.71, 95% CI 1.04–2.80, p = 0.03). Sex modified the association of peak CRP with both death and ICU admission, with stronger associations observed in men compared with women (death: OR 9.19, 95% CI 4.29–19.7, p <0.0001 in men vs OR 2.81, 95% CI 1.52–5.18, p = 0.009 in women, Pinteraction = 0.02). Conclusions In a sample of 781 men and women hospitalized with COVID-19 infection, men exhibited more robust inflammatory activation as evidenced by higher initial and peak inflammatory markers, as well as worse clinical outcomes. Better understanding of sex differences in immune responses to COVID-19 infection may shed light on the pathophysiology of COVID-19 infection.