Coronary artery calcium as a marker of healthy and unhealthy aging in adults aged 75 and older: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND AIMS: Coronary artery calcium (CAC) is validated for risk prediction among middle-aged adults, but there is limited research exploring implications of CAC among older adults. We used data from the Atherosclerosis Risk in Communities (ARIC) study to evaluate the association of CAC with domains of healthy and unhealthy aging in adults aged ≥75 years. METHODS: We included 2,290 participants aged ≥75 years free of known coronary heart disease who underwent CAC scoring at study visit 7. We examined the cross-sectional association of CAC = 0, 1-999 (reference), and ≥1000 with seven domains of aging: cognitive function, hearing, ankle-brachial index (ABI), pulse-wave velocity (PWV), forced vital capacity (FVC), physical functioning, and grip strength. RESULTS: The mean age was 80.5 ± 4.3 years, 38.6% male, and 77.7% White. 10.3% had CAC = 0 and 19.2% had CAC≥1000. Individuals with CAC = 0 had the lowest while those with CAC≥1000 had the highest proportion with dementia (2% vs 8%), hearing impairment (46% vs 67%), low ABI (3% vs 18%), high PWV (27% vs 41%), reduced FVC (34% vs 42%), impaired grip strength (66% vs 74%), and mean composite abnormal aging score (2.6 vs 3.7). Participants with CAC = 0 were less likely to have abnormal ABI (aOR:0.15, 95%CI:0.07-0.34), high PWV (aOR:0.57, 95%CI:0.41-0.80), and reduced FVC (aOR:0.69, 95%CI:0.50-0.96). Conversely, participants with CAC≥1000 were more likely to have low ABI (aOR:1.74, 95%CI:1.27-2.39), high PWV (aOR:1.52, 95%CI:1.15-2.00), impaired physical functioning (aOR:1.35, 95%CI:1.05-1.73), and impaired grip strength (aOR:1.46, 95%CI:1.08-1.99). CONCLUSIONS: Our findings highlight CAC as a simple measure broadly associated with biological aging, with clinical and research implications for estimating the physical and physiological aging trajectory of older individuals.

Universal Risk Prediction for Individuals With and Without Atherosclerotic Cardiovascular Disease.

BACKGROUND: American College of Cardiology/American Heart Association guidelines recommend distinct risk classification systems for primary and secondary cardiovascular disease prevention. However, both systems rely on similar predictors (eg, age and diabetes), indicating the possibility of a universal risk prediction approach for major adverse cardiovascular events (MACEs). OBJECTIVES: The authors examined the performance of predictors in persons with and without atherosclerotic cardiovascular disease (ASCVD) and developed and validated a universal risk prediction model. METHODS: Among 9,138 ARIC (Atherosclerosis Risk In Communities) participants with (n = 609) and without (n = 8,529) ASCVD at baseline (1996-1998), we examined established predictors in the risk classification systems and other predictors, such as body mass index and cardiac biomarkers (troponin and natriuretic peptide), using Cox models with MACEs (myocardial infarction, stroke, and heart failure). We also evaluated model performance. RESULTS: Over a follow-up of approximately 20 years, there were 3,209 MACEs (2,797 for no prior ASCVD). Most predictors showed similar associations with MACE regardless of baseline ASCVD status. A universal risk prediction model with the predictors (eg, established predictors, cardiac biomarkers) identified by least absolute shrinkage and selection operator regression and bootstrapping showed good discrimination for both groups (c-statistics of 0.747 and 0.691, respectively), and risk classification and showed excellent calibration, irrespective of ASCVD status. This universal prediction approach identified individuals without ASCVD who had a higher risk than some individuals with ASCVD and was validated externally in 5,322 participants in the MESA (Multi-Ethnic Study of Atherosclerosis). CONCLUSIONS: A universal risk prediction approach performed well in persons with and without ASCVD. This approach could facilitate the transition from primary to secondary prevention by streamlining risk classification and discussion between clinicians and patients.

Prevalence of Aortic Valve Calcium and the Long-Term Risk of Incident Severe Aortic Stenosis.

BACKGROUND: Aortic valve calcification (AVC) is a principal mechanism underlying aortic stenosis (AS). OBJECTIVES: This study sought to determine the prevalence of AVC and its association with the long-term risk for severe AS. METHODS: Noncontrast cardiac computed tomography was performed among 6,814 participants free of known cardiovascular disease at MESA (Multi-Ethnic Study of Atherosclerosis) visit 1. AVC was quantified using the Agatston method, and normative age-, sex-, and race/ethnicity-specific AVC percentiles were derived. The adjudication of severe AS was performed via chart review of all hospital visits and supplemented with visit 6 echocardiographic data. The association between AVC and long-term incident severe AS was evaluated using multivariable Cox HRs. RESULTS: AVC was present in 913 participants (13.4%). The probability of AVC >0 and AVC scores increased with age and were generally highest among men and White participants. In general, the probability of AVC >0 among women was equivalent to men of the same race/ethnicity who were approximately 10 years younger. Incident adjudicated severe AS occurred in 84 participants over a median follow-up of 16.7 years. Higher AVC scores were exponentially associated with the absolute risk and relative risk of severe AS with adjusted HRs of 12.9 (95% CI: 5.6-29.7), 76.4 (95% CI: 34.3-170.2), and 380.9 (95% CI: 169.7-855.0) for AVC groups 1 to 99, 100 to 299, and ≥300 compared with AVC = 0. CONCLUSIONS: The probability of AVC >0 varied significantly by age, sex, and race/ethnicity. The risk of severe AS was exponentially higher with higher AVC scores, whereas AVC = 0 was associated with an extremely low long-term risk of severe AS. The measurement of AVC provides clinically relevant information to assess an individual's long-term risk for severe AS.

Cardiovascular risk stratification among individuals with obesity: The Coronary Artery Calcium Consortium.

OBJECTIVE: The effectiveness of coronary artery calcification (CAC) for risk stratification in obesity, in which imaging is often limited because of a reduced signal to noise ratio, has not been well studied. METHODS: Data from 9334 participants (mean age: 53.3 ± 9.7 years; 67.9% men) with BMI ≥ 30 kg/m2 from the CAC Consortium, a retrospectively assembled cohort of individuals with no prior cardiovascular diseases (CVD), were used. The predictive value of CAC for all-cause and cause-specific mortality was evaluated using multivariable-adjusted Cox proportional hazards and competing-risks regression. RESULTS: Mean BMI was 34.5 (SD 4.4) kg/m2 (22.7% Class II and 10.8% Class III obesity), and 5461 (58.5%) had CAC. Compared with CAC = 0, those with CAC = 1-99, 100-299, and ≥300 Agatston units had higher rates (per 1000 person-years) of all-cause (1.97 vs. 3.5 vs. 5.2 vs. 11.3), CVD (0.4 vs. 1.1 vs. 1.5 vs. 4.2), and coronary heart disease (CHD) mortality (0.2 vs. 0.6 vs. 0.6 vs. 2.5), respectively, after mean follow-up of 10.8 ± 3.0 years. After adjusting for traditional cardiovascular risk factors, CAC ≥ 300 was associated with significantly higher risk of all-cause (hazard ratio [HR]: 2.05; 95% CI: 1.49-2.82), CVD (subdistribution HR: 3.48; 95% CI: 1.81-6.70), and CHD mortality (subdistribution HR: 5.44; 95% CI: 2.02-14.66), compared with CAC = 0. When restricting the sample to individuals with BMI ≥ 35 kg/m2 , CAC ≥ 300 remained significantly associated with the highest risk. CONCLUSIONS: Among individuals with obesity, including moderate-severe obesity, CAC strongly predicts all-cause, CVD, and CHD mortality and may serve as an effective cardiovascular risk stratification tool to prioritize the allocation of therapies for weight management.

Investigating the association of traditional and non-traditional tobacco product use with subclinical and clinical cardiovascular disease: The Cross-Cohort Collaboration-Tobacco working group rationale, design, and methodology.

While the impact of combustible cigarette smoking on cardiovascular disease (CVD) is well-established, the longitudinal association of non-traditional tobacco products with subclinical and clinical CVD has not been fully explored due to: 1) limited data availability; and 2) the lack of well-phenotyped prospective cohorts. Therefore, there is the need for sufficiently powered well-phenotyped datasets to fully elucidate the CVD risks associated with non-cigarette tobacco products. The Cross-Cohort Collaboration (CCC)-Tobacco is a harmonized dataset of 23 prospective cohort studies predominantly in the US. A priori defined variables collected from each cohort included baseline characteristics, details of traditional and non-traditional tobacco product use, inflammatory markers, and outcomes including subclinical and clinical CVD. The definitions of the variables in each cohort were systematically evaluated by a team of two physician-scientists and a biostatistician. Herein, we describe the method of data acquisition and harmonization and the baseline sociodemographic and risk profile of participants in the combined CCC-Tobacco dataset. The total number of participants in the pooled cohort is 322782 (mean age: 59.7 ± 11.8 years) of which 76% are women. White individuals make up the majority (73.1%), although there is good representation of other race and ethnicity groups including African American (15.6%) and Hispanic/Latino individuals (6.4%). The prevalence of participants who never smoked, formerly smoked, and currently smoke combustible cigarettes is 50%, 36%, and 14%, respectively. The prevalence of current and former cigar, pipe, and smokeless tobacco is 7.3%, 6.4%, and 8.6%, respectively. E-cigarette use was measured only in follow-up visits of select studies, totaling 1704 former and current users. CCC-Tobacco is a large, pooled cohort dataset that is uniquely designed with increased power to expand knowledge regarding the association of traditional and non-traditional tobacco use with subclinical and clinical CVD, with extension to understudied groups including women and individuals from underrepresented racial-ethnic groups.

Coronary Artery Calcium Scores in Older Adults With Diabetes and Their Association With Diabetes-Specific Risk Enhancers (from the Atherosclerosis Risk in Communities Study).

Coronary artery calcium (CAC) is a validated marker of atherosclerotic cardiovascular disease (ASCVD) risk; however, it is not routinely incorporated in ASCVD risk prediction in older adults with diabetes. We sought to assess the CAC distribution among this demographic and its association with "diabetes-specific risk enhancers," which are known to be associated with increased ASCVD risk. We used the ARIC (Atherosclerosis Risk in Communities) study data, including adults aged >75 years with diabetes, who had their CAC measured at ARIC visit 7 (2018 to 2019). The demographic characteristics of participants and their CAC distribution were analyzed using descriptive statistics. Multivariable-adjusted logistic regression models were used to estimate the association between diabetes-specific risk enhancers (duration of diabetes, albuminuria, chronic kidney disease, retinopathy, neuropathy, and ankle-brachial index) and elevated CAC, adjusting for age, gender, race, education level, dyslipidemia, hypertension, physical activity, smoking status, and family history of coronary heart disease. The mean age in our sample was 79.9 (SD 3.97) years, with 56.6% women and 62.1% White. The CAC scores were heterogenous, and the median CAC score was higher in participants with a greater number of diabetes risk enhancers, regardless of gender. In the multivariable-adjusted logistic regression models, participants with ≥2 diabetes-specific risk enhancers had greater odds of elevated CAC than those with <2 (odds ratio 2.31, 95% confidence interval 1.34 to 3.98). In conclusion, the distribution of CAC was heterogeneous among older adults with diabetes, with the CAC burden associated with the number of diabetes risk-enhancing factors present. These data may have implications for prognostication in older patients with diabetes and supports the possible incorporation of CAC in the assessment of cardiovascular disease risk in this population.

Coronary Artery Calcium Dispersion and Cause-Specific Mortality.

Coronary artery calcium (CAC) measures subclinical atherosclerosis and improves risk stratification. CAC characteristics-including vessel(s) involved, number of vessels, volume, and density-have been shown to differentially impact risk. We assessed how dispersion-either the number of calcified vessels or CAC phenotype (diffuse, normal, and concentrated)-impacted cause-specific mortality. The CAC Consortium is a retrospective cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC scoring. This study included patients with CAC >0 (n = 28,147). CAC area, CAC density, and CAC phenotypes (derived from the index of diffusion = 1 - [CAC in most concentrated vessel/total Agatston score]) were calculated. The associations between CAC characteristics and cause-specific mortality were assessed. The participant details included (n = 28,147): mean age 58.3 years, 25% female, 89.6% White, and 66% had 2+ calcified vessels. Diabetes, hypertension, and hyperlipidemia were predictors of multivessel involvement (p <0.001). After controlling for the overall CAC score, those with 4-vessel CAC involvement had more CAC area and less dense calcifications than those with 1-vessel. There was a graded increase in all-cause and cardiovascular disease (CVD)- and CHD-specific mortality as the number of calcified vessels increased. Among those with ≥2 vessels involved (n = 18,516), a diffuse phenotype was associated with a higher CVD-specific mortality and had a trend toward higher all-cause and CHD-specific mortality than a concentrated CAC phenotype. Diffuse CAC involvement was characterized by less dense calcification, more CAC area, multiple coronary vessel involvement, and presence of certain traditional risk factors. There is a graded increase in all-cause and CVD- and CHD-specific mortality with increasing CAC dispersion.

A Simple Approach to the Identification of Guideline-Based Coronary Artery Calcium Score Percentiles (From the Multi-Ethnic Study of Atherosclerosis).

Absolute coronary artery calcium (CAC) scores and CAC percentiles can identify different patient groups, which could be confusing in clinical practice. We aimed to create a simple "rule of thumb" for identifying the American College of Cardiology/American Heart Association endorsed 75th CAC percentile based on age, gender, and the absolute CAC score. Using the Multi-Ethnic Study of Atherosclerosis, we calculated the age and gender-specific percent likelihood that a guideline-based absolute CAC score group (1 to 100, 100 to 300, >300) will place a patient above the 75th percentile. Also, we derived gender-specific age cutoffs by which 95% of participants with any (>0), moderate (≥100), or severe (≥300) CAC score would be over the 75th percentile. We repeated the analysis using the 90th percentile threshold and also conducted sensitivity analyses stratified by race. Any CAC >0 places 95% of women younger than 60 years and over 90% of men younger than 50 years over the 75th percentile. Moderate absolute CAC scores (>100) place nearly all men <60 years and all women <70 years over the 75th percentile. Confirmatory analysis for age cutoffs was consistent with primary analysis, with cutoffs of 48 years for men and 59 years for women indicating a 95% likelihood that any CAC would place patients over the 75th percentile. In conclusion, our study provides a simple rule of thumb (men <50 years and women <60 years with any CAC, men <60 years and women <70 years with CAC >100) for identifying CAC >75th percentile that might be readily adopted in clinical practice.

Discordance Between Coronary Artery Calcium Area and Density Predicts Long-Term Atherosclerotic Cardiovascular Disease Risk.

BACKGROUND: Coronary artery calcium (CAC) is commonly quantified as the product of 2 generally correlated measures: plaque area and calcium density. OBJECTIVES: The authors sought to determine whether discordance between calcium area and density has long-term prognostic importance in atherosclerotic cardiovascular disease (ASCVD) risk. METHODS: The authors studied 10,373 primary prevention participants from the CAC Consortium with CAC >0. Based on their median values, calcium area and mean calcium density were divided into 4 mutually exclusive concordant/discordant groups. Cox proportional hazards regression assessed the association of calcium area/density groups with ASCVD mortality over a median of 11.7 years, adjusting for traditional risk factors and the Agatston CAC score. RESULTS: The mean age was 56.7 years, and 24% were female. The prevalence of plaque discordance was 19% (9% low calcium area/high calcium density, 10% high calcium area/low calcium density). Female sex (odds ratio [OR]: 1.48 [95% CI: 1.27-1.74]) and body mass index (OR: 0.81 [95% CI: 0.76-0.87], per 5 kg/m2 higher) were significantly associated with high calcium density discordance, whereas diabetes (OR: 2.23 [95% CI: 1.85-3.19]) was most strongly associated with discordantly low calcium density. Compared to those with low calcium area/low calcium density, individuals with low calcium area/high calcium density had a 71% lower risk of ASCVD death (HR: 0.29 [95% CI: 0.09-0.95]). CONCLUSIONS: For a given CAC score, high calcium density relative to plaque area confers lower long-term ASCVD risk, likely serving as an imaging marker of biological resilience for lesion vulnerability. Additional research is needed to define a robust definition of calcium area/density discordance for routine clinical risk prediction.

Sex-and race-specific burden of aortic valve calcification among older adults without overt coronary heart disease: The Atherosclerosis Risk in Communities Study.

BACKGROUND AND AIMS: The prevalence of aortic valve calcification (AVC) increases with age. However, the sex-and race-specific burden of AVC and associated cardiovascular risk factors among adults ≥75 years are not well studied. METHODS: We calculated the sex-and race-specific burden of AVC among 2283 older Black and White adults (mean age:80.5 [SD:4.3] years) without overt coronary heart disease from the Atherosclerosis Risk in Communities Study who underwent non-contrast cardiac-gated CT-imaging at visit 7 (2018-2019). Using Poisson regression with robust variance, we calculated the adjusted prevalence ratios (aPR) of the association of AVC with cardiovascular risk factors. RESULTS: The overall AVC prevalence was 44.8%, with White males having the highest prevalence at 58.2%. The prevalence was similar for Black males (40.5%), White females (38.9%), and Black females (36.8%). AVC prevalence increased significantly with age among all race-sex groups. The probability of any AVC at age 80 years was 55.4%, 40.0%, 37.3%, and 36.2% for White males, Black males, White females, and Black females, respectively. Among persons with prevalent AVC, White males had the highest median AVC score (100.9 Agatston Units [AU]), followed by Black males (68.5AU), White females (52.3AU), and Black females (46.5AU). After adjusting for cardiovascular risk factors, Black males (aPR:0.53; 95%CI:0.33-0.83), White females (aPR:0.68; 95%CI:0.61-0.77), and Black females (aPR:0.49; 95%CI:0.31-0.77) had lower AVC prevalence compared to White males. In addition, systolic blood pressure, non-HDL-cholesterol, and lipoprotein (a) were independently associated with AVC, with no significant race/sex interactions. CONCLUSIONS: AVC, although highly prevalent, was not universally present in this cohort of older adults. White males had ∼50-60% higher prevalence than other race-sex groups. Moreover, cardiovascular risk factors measured in older age showed significant association with AVC.

Omega-3 fatty acids, subclinical atherosclerosis, and cardiovascular events: Implications for primary prevention.

BACKGROUND AND AIMS: High-dose eicosapentaenoic acid (EPA) therapy was beneficial in high-risk patients without clinical cardiovascular disease (CVD). Whether higher plasma levels of EPA and docosahexaenoic acid (DHA) have similar benefits in those without subclinical CVD is unclear. We aim to evaluate the interplay between plasma omega-3 fatty acids and coronary artery calcium (CAC) in relation to CVD events. METHODS: We examined 6568 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with plasma EPA and DHA levels and CAC measured at baseline. The primary outcome was incident CVD events (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Hazard ratios for the primary outcome were adjusted for potential confounder using Cox regression. RESULTS: Mean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher loge(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.94) and loge(DHA) (aHR = 0.79; 95% CI, 0.66-0.96) were independently associated with fewer CVD events. The difference in absolute CVD event rates between lowest vs. highest EPA tertile increased at higher CAC levels. The adjusted HR for highest vs. lowest EPA tertile within CAC = 0 was 1.02 (95% CI, 0.72-1.46), CAC = 1-99 was 0.71 (95% CI, 0.51-0.99), and CAC≥100 was 0.67 (95% CI, 0.52-0.84). A similar association was seen in tertiles of DHA by CAC category. CONCLUSIONS: In an ethnically diverse population free of clinical CVD, higher plasma omega-3 fatty acid levels were associated with fewer long-term CVD events. The absolute decrease in CVD events with higher omega-3 fatty acid levels was more apparent at higher CAC scores.

Distribution of Coronary Artery Calcium by Age, Sex, and Race Among Patients 30-45 Years Old.

BACKGROUND: Coronary artery calcium (CAC) is a measure of atherosclerotic burden and is well-validated for risk stratification in middle- to older-aged adults. Few studies have investigated CAC in younger adults, and there is no calculator for determining age-, sex-, and race-based percentiles among individuals aged <45 years. OBJECTIVES: The purpose of this study was to determine the probability of CAC >0 and develop age-sex-race percentiles for U.S. adults aged 30-45 years. METHODS: We harmonized 3 datasets-CARDIA (Coronary Artery Risk Development in Young Adults), the CAC Consortium, and the Walter Reed Cohort-to study CAC in 19,725 asymptomatic Black and White individuals aged 30-45 years without known atherosclerotic cardiovascular disease. After weighting each cohort equally, the probability of CAC >0 and age-sex-race percentiles of CAC distributions were estimated using nonparametric techniques. RESULTS: The prevalence of CAC >0 was 26% among White males, 16% among Black males, 10% among White females, and 7% among Black females. CAC >0 automatically placed all females at >90th percentile. CAC >0 placed White males at the 90th percentile at age 34 years compared with Black males at age 37 years. An interactive webpage allows one to enter an age, sex, race, and CAC score to obtain the corresponding estimated percentile. CONCLUSIONS: In a large cohort of U.S. adults aged 30-45 years without symptomatic atherosclerotic cardiovascular disease, the probability of CAC >0 varied by age, sex, and race. Estimated percentiles may help interpretation of CAC scores among young adults relative to their age-sex-race matched peers and can henceforth be included in CAC score reporting.

Coronary Artery Calcium for Risk Stratification of Sudden Cardiac Death: The Coronary Artery Calcium Consortium.

BACKGROUND: Coronary artery calcium (CAC) is a marker of plaque burden. Whether CAC improves risk stratification for incident sudden cardiac death (SCD) beyond atherosclerotic cardiovascular disease (ASCVD) risk factors is unknown. OBJECTIVES: SCD is a common initial manifestation of coronary heart disease (CHD); however, SCD risk prediction remains elusive. METHODS: The authors studied 66,636 primary prevention patients from the CAC Consortium. Multivariable competing risks regression and C-statistics were used to assess the association between CAC and SCD, adjusting for demographics and traditional risk factors. RESULTS: The mean age was 54.4 years, 33% were women, 11% were of non-White ethnicity, and 55% had CAC >0. A total of 211 SCD events (0.3%) were observed during a median follow-up of 10.6 years, 91% occurring among those with baseline CAC >0. Compared with CAC = 0, there was a stepwise higher risk (P trend < 0.001) in SCD for CAC 100 to 399 (subdistribution hazard ratio [SHR]: 2.8; 95% CI: 1.6-5.0), CAC 400 to 999 (SHR: 4.0; 95% CI: 2.2-7.3), and CAC >1,000 (SHR: 4.9; 95% CI: 2.6-9.9). CAC provided incremental improvements in the C-statistic for the prediction of SCD among individuals with a 10-year risk <7.5% (ΔC-statistic = +0.046; P = 0.02) and 7.5% to 20% (ΔC-statistic = +0.069; P = 0.003), which were larger when compared with persons with a 10-year risk >20% (ΔC-statistic = +0.01; P = 0.54). CONCLUSIONS: Higher CAC burden strongly associates with incident SCD beyond traditional risk factors, particularly among primary prevention patients with low-intermediate risk. SCD risk stratification can be useful in the early stages of CHD through the measurement of CAC, identifying patients most likely to benefit from further downstream testing.

National Trends in Use of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists by Cardiologists and Other Specialties, 2015 to 2020.

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) mitigate cardiovascular risk in individuals with type 2 diabetes, but most eligible patients do not receive them. We characterized temporal trends in SGLT2i and GLP-1RA use by cardiologists compared with other groups of clinicians. Methods and Results We conducted a descriptive analysis of serial, cross-sectional data derived from IQVIA's National Prescription Audit, a comprehensive audit capturing ≈90% of US retail prescription dispensing and projected to population-level data, to estimate monthly SGLT2is and GLP-1RAs dispensed from January 2015 to December 2020, stratified by prescriber specialty and molecule. We also used the American Medical Association's Physician Masterfile to calculate average annual SGLT2is and GLP-1RAs dispensed per physician. Between January 2015 and December 2020, a total of 63.2 million SGLT2i and 63.4 million GLP-1RA prescriptions were dispensed in the United States. Monthly prescriptions from cardiologists increased 12-fold for SGLT2is (from 2228 to 25 815) and 4-fold for GLP-1RAs (from 1927 to 6981). Nonetheless, cardiologists represented only 1.5% of SGLT2i prescriptions and 0.4% of GLP-1RA prescriptions in 2020, while total use was predominated by primary care physicians/internists (57% of 2020 SGLT2is and 52% of GLP-1RAs). Endocrinologists led in terms of prescriptions dispensed per physician in 2020 (272 SGLT2is and 405 GLP-1RAs). Cardiologists, but not noncardiologists, increasingly used SGLT2is over GLP-1RAs, with accelerated uptake of empagliflozin and dapagliflozin coinciding with their landmark cardiovascular outcomes trials and subsequent US Food and Drug Administration label expansions. Conclusions While use of SGLT2is and GLP-1RAs by cardiologists in the United States increased substantially over a 6-year period, cardiologists still account for a very small proportion of all use, contributing to marked undertreatment of individuals with type 2 diabetes at high cardiovascular risk.

The Interplay of Race/Ethnicity and Obesity on the Incidence of Venous Thromboembolism.

INTRODUCTION: Factors predisposing asymptomatic individuals within the community to venous thromboembolism are not fully understood. This study characterizes the incidence and determinants of venous thromboembolism among the Multiethnic Study of Atherosclerosis cohort with a focus on race/ethnicity and obesity. METHODS: This study (analyzed in 2020-2021) used the Multiethnic Study of Atherosclerosis cohort (2000-2017), which included participants with diverse ethnic/racial backgrounds aged 45-84 years without cardiovascular disease at baseline. The primary endpoint was time to diagnosis of venous thromboembolism defined using International Classification of Diseases codes (415, 451, 453, 126, 180, and 182). Multivariable-adjusted hazard ratios of the predictors of venous thromboembolism were calculated with a focus on the interaction between obesity and race/ethnicity categories. RESULTS: Over a median follow-up period of 14 years, 233 individuals developed venous thromboembolism. Incidence rates (per 1,000 person-years) varied across racial/ethnic groups with the highest incidence among Black (4.02) followed by White (2.98), Hispanic (2.08), and Chinese (0.79) participants. There was a stepwise increase in the incidence rate of venous thromboembolism with increasing BMI regardless of race/ethnicity: normal (1.95), overweight (2.52), obese (3.63), and morbidly obese (4.55). The association between BMI and venous thromboembolism was strongest among non-White women with the highest incidence rate for obese (4.8) compared with non-obese (1.6). The interaction among obesity, gender, and race was statistically significant (p=0.01) in non-White obese women. Risk of venous thromboembolism increased with age for all race/ethnicities. CONCLUSIONS: This study finds that obesity may confer an increased risk for venous thromboembolism among non-White women compared with other groups-White men, White women, and non-White men.

Coronary artery calcium scores indicating secondary prevention level risk: Findings from the CAC consortium and FOURIER trial.

BACKGROUND AND AIMS: Coronary artery calcium (CAC) burden displays a stepwise association with atherosclerotic cardiovascular disease (ASCVD) risk. Among primary prevention patients, we sought to determine the CAC scores equivalent to ASCVD mortality rates observed in the FOURIER trial, a modern secondary prevention cohort. METHODS AND RESULTS: For the main analysis, we included participants from the CAC Consortium ≥50 years old with a 10-year ASCVD risk ≥7.5% (n = 20,207). Poisson regression was used to define the relationship between CAC and annual ASCVD mortality. Equations generated from the regression models were then used to derive CAC scores associated with equivalent annual ASCVD mortality as observed in FOURIER placebo participants from the overall trial and in key trial subgroups. The CAC Consortium participants had a similar age (65.5 versus 62.5 years) and sex (22% versus 24% female) distribution as FOURIER. The annualized ASCVD mortality rate in FOURIER participants (0.766 per 100 person-years) corresponded to a CAC score of 781 (418-1467). A CAC score of 255 (162-394) corresponded to an ASCVD mortality rate equivalent to the lowest risk FOURIER subgroup (presence of myocardial infarction >2 years prior to trial enrollment). No CAC score produced a risk equivalent to high-risk FOURIER subgroups, particularly those with symptomatic peripheral arterial disease and/or multivessel coronary heart disease. CONCLUSIONS: Primary prevention individuals with increased CAC burden may have annualized ASCVD mortality rates equivalent to persons with stable secondary prevention-level risk. These findings argue for a risk continuum between higher risk primary prevention and stable secondary prevention patients, as their ASCVD risks may overlap.

Coronary artery calcium is associated with increased risk for lung and colorectal cancer in men and women: the Multi-Ethnic Study of Atherosclerosis (MESA).

AIMS: This study explored the association of coronary artery calcium (CAC) with incident cancer subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA). CAC is an established predictor of cardiovascular disease (CVD), with emerging data also supporting independent predictive value for cancer. The association of CAC with risk for individual cancer subtypes is unknown. METHODS AND RESULTS: We included 6271 MESA participants, aged 45-84 and without known CVD or self-reported history of cancer. There were 777 incident cancer cases during mean follow-up of 12.9 ± 3.1 years. Lung and colorectal cancer (186 cases) were grouped based on their strong overlap with CVD risk profile; prostate (men) and ovarian, uterine, and breast cancer (women) were considered as sex-specific cancers (in total 250 cases). Incidence rates and Fine and Gray competing risks models were used to assess relative risk of cancer-specific outcomes stratified by CAC groups or Log(CAC+1). The mean age was 61.7 ± 10.2 years, 52.7% were women, and 36.5% were White. Overall, all-cause cancer incidence increased with CAC scores, with rates per 1000 person-years of 13.1 [95% confidence interval (CI): 11.7-14.7] for CAC = 0 and 35.8 (95% CI: 30.2-42.4) for CAC ≥400. Compared with CAC = 0, hazards for those with CAC ≥400 were increased for lung and colorectal cancer in men [subdistribution hazard ratio (SHR): 2.2 (95% CI: 1.1-4.7)] and women [SHR: 2.2 (95% CI: 1.0-4.6)], but not significantly for sex-specific cancers across sexes. CONCLUSION: CAC scores were associated with cancer risk in both sexes; however, this was stronger for lung and colorectal when compared with sex-specific cancers. Our data support potential synergistic use of CAC scores in the identification of both CVD and lung and colorectal cancer risk.