Cardiovascular Burden of the V142I Transthyretin Variant.

Importance: Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) gene, present in 3% to 4% of US Black individuals, increases heart failure (HF) and mortality risk. Precisely defining carrier risk across relevant clinical outcomes and estimating population burden of disease are important given established and emerging targeted treatments. Objectives: To better define the natural history of disease in carriers across mid to late life, assess variant modifiers, and estimate cardiovascular burden to the US population. Design, Setting, and Participants: A total of 23 338 self-reported Black participants initially free from HF were included in 4 large observational studies across the US (mean [SD], 15.5 [8.2] years of follow-up). Data analysis was performed between May 2023 and February 2024. Exposure: V142I carrier status (n = 754, 3.2%). Main Outcomes and Measures: Hospitalizations for HF (including subtypes of reduced and preserved ejection fraction) and all-cause mortality. Outcomes were analyzed by generating 10-year hazard ratios for each age between 50 and 90 years. Using actuarial methods, mean survival by carrier status was estimated and applied to the 2022 US population using US Census data. Results: Among the 23 338 participants, the mean (SD) age at baseline was 62 (9) years and 76.7% were women. Ten-year carrier risk increased for HF hospitalization by age 63 years, predominantly driven by HF with reduced ejection fraction, and 10-year all-cause mortality risk increased by age 72 years. Only age (but not sex or other select variables) modified risk with the variant, with estimated reductions in longevity ranging from 1.9 years (95% CI, 0.6-3.1) at age 50 to 2.8 years (95% CI, 2.0-3.6) at age 81. Based on these data, 435 851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957 505 years of life (95% CI, 534 475-1 380 535) due to the variant. Conclusions and Relevance: Among self-reported Black individuals, male and female V142I carriers faced similar and substantial risk for HF hospitalization, predominantly with reduced ejection fraction, and death, with steep age-dependent penetrance. Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation.

Epidemiology of Diabetes and Atherosclerotic Cardiovascular Disease Among Asian American Adults: Implications, Management, and Future Directions: A Scientific Statement From the American Heart Association.

Asian American individuals make up the fastest growing racial and ethnic group in the United States. Despite the substantial variability that exists in type 2 diabetes and atherosclerotic cardiovascular disease risk among the different subgroups of Asian Americans, the current literature, when available, often fails to examine these subgroups individually. The purpose of this scientific statement is to summarize the latest disaggregated data, when possible, on Asian American demographics, prevalence, biological mechanisms, genetics, health behaviors, acculturation and lifestyle interventions, pharmacological therapy, complementary alternative interventions, and their impact on type 2 diabetes and atherosclerotic cardiovascular disease. On the basis of available evidence to date, we noted that the prevalences of type 2 diabetes and stroke mortality are higher in all Asian American subgroups compared with non-Hispanic White adults. Data also showed that atherosclerotic cardiovascular disease risk is highest among South Asian and Filipino adults but lowest among Chinese, Japanese, and Korean adults. This scientific statement discusses the biological pathway of type 2 diabetes and the possible role of genetics in type 2 diabetes and atherosclerotic cardiovascular disease among Asian American adults. Challenges to provide evidence-based recommendations included the limited data on Asian American adults in risk prediction models, national surveillance surveys, and clinical trials, leading to significant research disparities in this population. The large disparity within this population is a call for action to the public health and clinical health care community, for whom opportunities for the inclusion of the Asian American subgroups should be a priority. Future studies of atherosclerotic cardiovascular disease risk in Asian American adults need to be adequately powered, to incorporate multiple Asian ancestries, and to include multigenerational cohorts. With advances in epidemiology and data analysis and the availability of larger, representative cohorts, furthering refining the Pooled Cohort Equations, in addition to enhancers, would allow better risk estimation in segments of the population. Last, this scientific statement provides individual- and community-level intervention suggestions for health care professionals who interact with the Asian American population.

General Anxiety Disorder-7 Questionnaire as a marker of low socioeconomic status and inequity.

BACKGROUND: The General Anxiety Disorder-7 (GAD-7) questionnaire is a standard tool used for screening and follow-up of patients with Generalized Anxiety Disorder (GAD). Although it is generally accepted that anxiety correlates with clinical and psychosocial stressors, precise quantitative data is limited on the relations among GAD-7, traditional biomarkers, and other measures of health. Further research is needed about how GAD-7 relates to race, ethnicity, and socioeconomic status (SES) as an assembly. We determined how multiple demographic and socioeconomic data correlate with the participants' GAD-7 results when compared with laboratory, physical function, clinical, and other biological markers. METHODS: The Project Baseline Health Study (BHS) is a prospective cohort of adults representing several populations in the USA. We analyzed a deeply phenotyped group of 2502 participants from that study. Measures of interest included: clinical markers or history of medical diagnoses; physical function markers including gait, grip strength, balance time, daily steps, and echocardiographic parameters; psychometric measurements; activities of daily living; socioeconomic characteristics; and laboratory results. RESULTS: Higher GAD-7 scores were associated with female sex, younger age, and Hispanic ethnicity. Measures of low SES were also associated with higher scores, including unemployment, income ≤$25,000, and ≤12 years of education. After adjustment for 158 demographic, clinical, laboratory, and symptom characteristics, unemployment and overall higher SES risk scores were highly correlated with anxiety scores. Protective factors included Black race and older age. LIMITATIONS: Correlations identified in this cross-sectional study cannot be used to infer causal relationships; further, we were not able to account for possible use of anxiety treatments by study participants. CONCLUSIONS: These findings highlight the importance of understanding anxiety as a biopsychosocial entity. Clinicians and provider organizations need to consider both the physical manifestations of the disorder and their patients' social determinants of health when considering treatment pathways and designing interventions.

Are risk factors necessary for pretest probability assessment of coronary artery disease? A patient similarity network analysis of the PROMISE trial.

BACKGROUND: Pretest probability (PTP) calculators utilize epidemiological-level findings to provide patient-level risk assessment of obstructive coronary artery disease (CAD). However, their limited accuracies question whether dissimilarities in risk factors necessarily result in differences in CAD. Using patient similarity network (PSN) analyses, we wished to assess the accuracy of risk factors and imaging markers to identify ≥50% luminal narrowing on coronary CT angiography (CCTA) in stable chest-pain patients. METHODS: We created four PSNs representing: patient characteristics, risk factors, non-coronary imaging markers and calcium score. We used spectral clustering to group individuals with similar risk profiles. We compared PSNs to a contemporary PTP score incorporating calcium score and risk factors to identify ≥50% luminal narrowing on CCTA in the CT-arm of the PROMISE trial. We also conducted subanalyses in different age and sex groups. RESULTS: In 3556 individuals, the calcium score PSN significantly outperformed patient characteristic, risk factor, and non-coronary imaging marker PSNs (AUC: 0.81 vs. 0.57, 0.55, 0.54; respectively, p â€‹< â€‹0.001 for all). The calcium score PSN significantly outperformed the contemporary PTP score (AUC: 0.81 vs. 0.78, p â€‹< â€‹0.001), and using 0, 1-100 and â€‹> â€‹100 cut-offs provided comparable results (AUC: 0.81 vs. 0.81, p â€‹= â€‹0.06). Similar results were found in all subanalyses. CONCLUSION: Calcium score on its own provides better individualized obstructive CAD prediction than contemporary PTP scores incorporating calcium score and risk factors. Risk factors may not be able to improve the diagnostic accuracy of calcium score to predict ≥50% luminal narrowing on CCTA.

Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. RESULTS: Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Risk Factor Burden and Long-Term Prognosis of Patients With Premature Coronary Artery Disease.

Background Coronary artery disease (CAD) is increasing among young adults. We aimed to describe the cardiovascular risk factors and long-term prognosis of premature CAD. Methods and Results Using the Duke Databank for Cardiovascular Disease, we evaluated 3655 patients admitted between 1995 and 2013 with a first diagnosis of obstructive CAD before the age of 50 years. Major adverse cardiovascular events (MACEs), defined as the composite of death, myocardial infarction, stroke, or revascularization, were ascertained for up to 10 years. Cox proportional hazard regression models were used to assess associations with the rate of first recurrent event, and negative binomial log-linear regression was used for rate of multiple event recurrences. Past or current smoking was the most frequent cardiovascular factor (60.8%), followed by hypertension (52.8%) and family history of CAD (39.8%). Within a 10-year follow-up, 52.9% of patients had at least 1 MACE, 18.6% had at least 2 recurrent MACEs, and 7.9% had at least 3 recurrent MACEs, with death occurring in 20.9% of patients. Across follow-up, 31.7% to 37.2% of patients continued smoking, 81.7% to 89.3% had low-density lipoprotein cholesterol levels beyond the goal of 70 mg/dL, and 16% had new-onset diabetes mellitus. Female sex, diabetes mellitus, chronic kidney disease, multivessel disease, and chronic inflammatory disease were factors associated with recurrent MACEs. Conclusions Premature CAD is an aggressive disease with frequent ischemic recurrences and premature death. Individuals with premature CAD have a high proportion of modifiable cardiovascular risk factors, but failure to control them is frequently observed.

A novel approach for measuring residential socioeconomic factors associated with cardiovascular and metabolic health.

Individual-level characteristics, including socioeconomic status, have been associated with poor metabolic and cardiovascular health; however, residential area-level characteristics may also independently contribute to health status. In the current study, we used hierarchical clustering to aggregate 444 US Census block groups in Durham, Orange, and Wake Counties, NC, USA into six homogeneous clusters of similar characteristics based on 12 demographic factors. We assigned 2254 cardiac catheterization patients to these clusters based on residence at first catheterization. After controlling for individual age, sex, smoking status, and race, there were elevated odds of patients being obese (odds ratio (OR)=1.92, 95% confidence intervals (CI)=1.39, 2.67), and having diabetes (OR=2.19, 95% CI=1.57, 3.04), congestive heart failure (OR=1.99, 95% CI=1.39, 2.83), and hypertension (OR=2.05, 95% CI=1.38, 3.11) in a cluster that was urban, impoverished, and unemployed, compared with a cluster that was urban with a low percentage of people that were impoverished or unemployed. Our findings demonstrate the feasibility of applying hierarchical clustering to an assessment of area-level characteristics and that living in impoverished, urban residential clusters may have an adverse impact on health.

Sex Differences in Demographics, Risk Factors, Presentation, and Noninvasive Testing in Stable Outpatients With Suspected Coronary Artery Disease: Insights From the PROMISE Trial.

OBJECTIVES: The aim of this study was to determine whether presentation, risk assessment, testing choices, and results differ by sex in stable symptomatic outpatients with suspected coronary artery disease (CAD). BACKGROUND: Although established CAD presentations differ by sex, little is known about stable, suspected CAD. METHODS: The characteristics of 10,003 men and women in the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial were compared using chi-square and Wilcoxon rank-sum tests. Sex differences in test selection and predictors of test positivity were examined using logistic regression. RESULTS: Women were older (62.4 years of age vs. 59.0 years of age) and were more likely to be hypertensive (66.6% vs. 63.2%), dyslipidemic (68.9% vs. 66.3%), and to have a family history of premature CAD (34.6% vs. 29.3) (all p values <0.005). Women were less likely to smoke (45.6% vs. 57.0%; p < 0.001), although their prevalence of diabetes was similar to that in men (21.8% vs. 21.0%; p = 0.30). Chest pain was the primary symptom in 73.2% of women versus 72.3% of men (p = 0.30), and was characterized as "crushing/pressure/squeezing/tightness" in 52.5% of women versus 46.2% of men (p < 0.001). Compared with men, all risk scores characterized women as being at lower risk, and providers were more likely to characterize women as having a low (<30%) pre-test probability of CAD (40.7% vs. 34.1%; p < 0.001). Compared with men, women were more often referred to imaging tests (adjusted odds ratio: 1.21; 95% confidence interval: 1.01 to 1.44) than nonimaging tests. Women were less likely to have a positive test (9.7% vs. 15.1%; p < 0.001). Although univariate predictors of test positivity were similar, in multivariable models, age, body mass index, and Framingham risk score were predictive of a positive test in women, whereas Framingham and Diamond and Forrester risk scores were predictive in men. CONCLUSIONS: Patient sex influences the entire diagnostic pathway for possible CAD, from baseline risk factors and presentation to noninvasive test outcomes. These differences highlight the need for sex-specific approaches for the evaluation of CAD.

A Guide for a Cardiovascular Genomics Biorepository: the CATHGEN Experience.

The CATHeterization GENetics (CATHGEN) biorepository was assembled in four phases. First, project start-up began in 2000. Second, between 2001 and 2010, we collected clinical data and biological samples from 9334 individuals undergoing cardiac catheterization. Samples were matched at the individual level to clinical data collected at the time of catheterization and stored in the Duke Databank for Cardiovascular Diseases (DDCD). Clinical data included the following: subject demographics (birth date, race, gender, etc.); cardiometabolic history including symptoms; coronary anatomy and cardiac function at catheterization; and fasting chemistry data. Third, as part of the DDCD regular follow-up protocol, yearly evaluations included interim information: vital status (verified via National Death Index search and supplemented by Social Security Death Index search), myocardial infarction (MI), stroke, rehospitalization, coronary revascularization procedures, medication use, and lifestyle habits including smoking. Fourth, samples were used to generate molecular data. CATHGEN offers the opportunity to discover biomarkers and explore mechanisms of cardiovascular disease.

Prevalence and management of hypertension in acute coronary syndrome patients varies by sex: observations from the Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes (SYMPHONY) randomized clinical trials.

BACKGROUND: Hypertension affects 1 billion individuals worldwide and is an independent risk factor for death after acute coronary syndromes (ACS). METHODS: We examined the prevalence and medical treatment of hypertension among 15,904 ACS patients randomized in the SYMPHONY and 2nd SYMPHONY trials. Analyses were performed overall and according to sex for the United States and across international practice. Multivariable models identified factors associated with use of antihypertensive medication classes and examined the association of hypertension and sex with mortality. RESULTS: In the United States, hypertension was more prevalent in women than in men, overall (63% vs 50%) and within every decile of age. Hypertensive women more often received calcium-channel blockers (35% vs 30%) and diuretics (33% vs 19%) and less often received beta-blockers (51% vs 57%). Angiotensin-converting enzyme inhibitor use was similar (35% vs 34%). Women received multiple agents more frequently than did men: 2 agents, 35% vs 30%; > or = 3 agents, 16% vs 13%. Female sex independently predicted drug-class use only for diuretics. Mortality was higher in hypertensive women than in hypertensive men; after multivariable adjustment, mortality was similar without evidence of a differential association between hypertension and mortality according to sex. Although there was international variation in the use of individual classes of agents, the overall findings by sex were similar across regions. CONCLUSION: Hypertension is more prevalent in women than in men with ACS, and its medical management varies by sex, but its association with mortality is similar. Opportunities exist to improve medical therapy and outcomes in women with hypertension.