Very High Coronary Artery Calcium (≥1000) and Association With Cardiovascular Disease Events, Non-Cardiovascular Disease Outcomes, and Mortality: Results From MESA.

BACKGROUND: There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations. METHODS: Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). RESULTS: Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm2), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups. CONCLUSIONS: Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.

Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019: The MESA Study (Multi-Ethnic Study of Atherosclerosis).

BACKGROUND: Recent American College of Cardiology/American Heart Association Primary Prevention Guidelines recommended considering low-dose aspirin therapy only among adults 40 to 70 years of age who are at higher atherosclerotic cardiovascular disease (ASCVD) risk but not at high risk of bleeding. However, it remains unclear how these patients are best identified. The present study aimed to assess the value of coronary artery calcium (CAC) for guiding aspirin allocation for primary prevention by using 2019 aspirin meta-analysis data on cardiovascular disease relative risk reduction and bleeding risk. METHODS: The study included 6470 participants from the MESA Study (Multi-Ethnic Study of Atherosclerosis). ASCVD risk was estimated using the pooled cohort equations, and 3 strata were defined: <5%, 5% to 20%, and >20%. All participants underwent CAC scoring at baseline, and CAC scores were stratified as =0, 1 to 99, ≥100, and ≥400. A 12% relative risk reduction in cardiovascular disease events was used for the 5-year number needed to treat (NNT5) calculations, and a 42% relative risk increase in major bleeding events was used for the 5-year number needed to harm (NNH5) estimations. RESULTS: Only 5% of MESA participants would qualify for aspirin consideration for primary prevention according to the American College of Cardiology/American Heart Association guidelines and using >20% estimated ASCVD risk to define higher risk. Benefit/harm calculations were restricted to aspirin-naive participants <70 years of age not at high risk of bleeding (n=3540). The overall NNT5 with aspirin to prevent 1 cardiovascular disease event was 476 and the NNH5 was 355. The NNT5 was also greater than or similar to the NNH5 among estimated ASCVD risk strata. Conversely, CAC≥100 and CAC≥400 identified subgroups in which NNT5 was lower than NNH5. This was true both overall (for CAC≥100, NNT5=140 versus NNH5=518) and within ASCVD risk strata. Also, CAC=0 identified subgroups in which the NNT5 was much higher than the NNH5 (overall, NNT5=1190 versus NNH5=567). CONCLUSIONS: CAC may be superior to the pooled cohort equations to inform the allocation of aspirin in primary prevention. Implementation of current 2019 American College of Cardiology/American Heart Association guideline recommendations together with the use of CAC for further risk assessment may result in a more personalized, safer allocation of aspirin in primary prevention. Confirmation of these findings in experimental settings is needed.

Fitness and prostate cancer screening, incidence, and mortality: Results from the Henry Ford Exercise Testing (FIT) Project.

BACKGROUND: The relation between cardiorespiratory fitness (CRF) and prostate cancer is not well established. The objective of this study was to determine whether CRF is associated with prostate cancer screening, incidence, or mortality. METHODS: The Henry Ford Exercise Testing Project is a retrospective cohort study of men aged 40 to 70 years without cancer who underwent physician-referred exercise stress testing from 1995 to 2009. CRF was quantified in metabolic equivalents of task (METs) (<6 [reference], 6-9, 10-11, and ≥12 METs), estimated from the peak workload achieved during a symptom-limited, maximal exercise stress test. Prostate-specific antigen (PSA) testing, incident prostate cancer, and all-cause mortality were analyzed with multivariable adjusted Poisson regression and Cox proportional hazard models. RESULTS: In total, 22,827 men were included, of whom 739 developed prostate cancer, with a median follow-up of 7.5 years. Men who had high fitness (≥12 METs) had an 28% higher risk of PSA screening (95% CI, 1.2-1.3) compared with those who had low fitness (<6 METs. After adjusting for PSA screening, fitness was associated with higher prostate cancer incidence (men aged <55 years, P = .02; men aged >55 years, P ≤ .01), but not with advanced prostate cancer. Among the men who were diagnosed with prostate cancer, high fitness was associated with a 60% lower risk of all-cause mortality (95% CI, 0.2-0.9). CONCLUSIONS: Although men with high fitness are more likely to undergo PSA screening, this does not fully account for the increased incidence of prostate cancer seen among these individuals. However, men with high fitness have a lower risk of death after a prostate cancer diagnosis, suggesting that the cancers identified may be low-risk with little impact on long-term outcomes.

Characterization of Volatile Organic Compound Metabolites in Cigarette Smokers, Electronic Nicotine Device Users, Dual Users, and Nonusers of Tobacco.

INTRODUCTION: Limited research exists about the possible cardiovascular effects of electronic nicotine delivery systems (ENDS). We therefore sought to compare exposure to known or potentially cardiotoxic volatile organic compounds (VOCs) in ENDS users, smokers, and dual users. METHODS: A total of 371 individuals from the Cardiovascular Injury due to Tobacco Use study, a cross-sectional study of healthy participants aged 21-45 years, were categorized as nonusers of tobacco (n = 87), sole ENDS users (n = 17), cigarette smokers (n = 237), and dual users (n = 30) based on 30-day self-reported tobacco product use patterns. Participants provided urine samples for VOC and nicotine metabolite measurement. We assessed associations between tobacco product use and VOC metabolite measures using multivariable-adjusted linear regression models. RESULTS: Mean (SD) age of the population was 32 (±6.8) years, 55% men. Mean urinary cotinine level in nonusers of tobacco was 2.6 ng/mg creatinine, whereas cotinine levels were similar across all tobacco product use categories (851.6-910.9 ng/mg creatinine). In multivariable-adjusted models, sole ENDS users had higher levels of metabolites of acrolein, acrylamide, acrylonitrile, and xylene compared with nonusers of tobacco, but lower levels of most VOC metabolites compared with cigarette smokers or dual users. In direct comparison of cigarettes smokers and dual users, we found lower levels of metabolites of styrene and xylene in dual users. CONCLUSION: Although sole ENDS use may be associated with lower VOC exposure compared to cigarette smoking, further study is required to determine the potential health effects of the higher levels of certain reactive aldehydes, including acrolein, in ENDS users compared with nonusers of tobacco. IMPLICATIONS: ENDS use in conjunction with other tobacco products may not significantly reduce exposure to VOC, but sole use does generally reduce some VOC exposure and warrants more in-depth studies.

Cardiorespiratory fitness and incident lung and colorectal cancer in men and women: Results from the Henry Ford Exercise Testing (FIT) cohort.

BACKGROUND: To the authors' knowledge, the relationship between cardiorespiratory fitness (CRF) and lung and colorectal cancer outcomes is not well established. METHODS: A retrospective cohort study was performed of 49,143 consecutive patients who underwent clinician-referred exercise stress testing from 1991 through 2009. The patients ranged in age from 40 to 70 years, were without cancer, and were treated within the Henry Ford Health System in Detroit, Michigan. CRF, measured in metabolic equivalents of task (METs), was categorized as <6 (reference), 6 to 9, 10 to 11, and ≥12. Incident cancer was obtained through linkage to the cancer registry and all-cause mortality from the National Death Index. RESULTS: Participants had a mean age of 54 ± 8 years. Approximately 46% were female, 64% were white, 29% were black, and 1% were Hispanic. The median follow-up was 7.7 years. Cox proportional hazard models, adjusted for age, race, sex, body mass index, smoking history, and diabetes, found that those in the highest fitness category (METs ≥12) had a 77% decreased risk of lung cancer (hazard ratio [HR], 0.23; 95% CI, 0.14-0.36) and a 61% decreased risk of incident colorectal cancer (HR, 0.39; 95% CI, 0.23-0.66; with additional adjustment for aspirin and statin use). Among those diagnosed with lung and colorectal cancer, those with high fitness had a decreased risk of subsequent death of 44% and 89%, respectively (HR, 0.56 [95% CI, 0.32-1.00] and HR, 0.11 [95% CI, 0.03-0.37], respectively). CONCLUSIONS: In what to the authors' knowledge is the largest study performed to date, higher CRF was associated with a lower risk of incident lung and colorectal cancer in men and women and a lower risk of all-cause mortality among those diagnosed with lung or colorectal cancer.

The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017.

BACKGROUND: E-cigarette use prevalence has grown rapidly in the US. Despite the popularity of these products, few acute exposure toxicity studies exist, and studies on long-term pulmonary health effects are limited. E-cigarette users who are never combustible cigarette smokers (sole users) constitute a unique group of young adults that may be at increased risk of bronchial hyperreactivity and development of asthma. Given the public health concern about the potential pulmonary health effects of sole e-cigarette use, we aimed to examine the association between e-cigarette use and asthma among never combustible cigarette smokers. METHODS: We pooled 2016 and 2017 data of the Behavioral Risk Factor Surveillance System (BRFSS), a large, cross-sectional telephone survey of adults aged 18 years and older in the U.S. We included 402,822 participants without any history of combustible cigarette smoking (defined as lifetime smoking < 100 cigarettes) and with complete self-reported information on key variables. Current e-cigarette use, further classified as daily or occasional use, was the primary exposure. The main outcome, asthma, was defined as self-reported history of asthma. We assess the relationship of sole e-cigarette use with asthma using multivariable logistic regression adjusting for age, sex, race, income, level of education and body mass index. RESULTS: Of 402,822 never combustible cigarette smokers, there were 3103 (0.8%) current e-cigarette users and 34,074 (8.5%) with asthma. The median age group of current e-cigarette users was 18-24 years. Current e-cigarette use was associated with 39% higher odds of self-reported asthma compared to never e-cigarette users (Odds Ratio [OR], 1.39; 95% confidence interval: 1.15, 1.68). There was a graded increased odds of having asthma with increase of e-cigarette use intensity. The odds ratio of self-reported asthma increased from 1.31 (95% confidence interval: 1.05, 1.62) in occasional users to 1.73 (95% confidence interval: 1.21, 2.48) in daily e-cigarette users, compared to never e-cigarette users. CONCLUSION: Our findings from a large, nationally representative survey suggest increased odds of asthma among never combustible smoking e-cigarette users. This may have potential public health implications, providing a strong rationale to support future longitudinal studies of pulmonary health in young e-cigarette-using adults.

Sex differences in calcified plaque and long-term cardiovascular mortality: observations from the CAC Consortium.

Aims: Pathologic evidence supports unique sex-specific mechanisms as precursors for acute cardiovascular (CV) events. Current evidence on long-term CV risk among women when compared with men based on measures of coronary artery calcium (CAC) remains incomplete. Methods and results: A total of 63 215 asymptomatic women and men were enrolled in the multicentre, CAC Consortium with median follow-up of 12.6 years. Pooled cohort equation (PCE) risk scores and risk factor data were collected with the Agatston score and other CAC measures (number of lesions and vessels, lesion size, volume, and plaque density). Cox proportional hazard models were employed to estimate CV mortality (n = 919). Sex interactions were calculated. Women and men had average PCE risk scores of 5.8% and 9.1% (P < 0.001). Within CAC subgroups, women had fewer calcified lesions (P < 0.0001) and vessels (P = 0.017), greater lesion size (P < 0.0001), and higher plaque density (P = 0.013) when compared with men. For women and men without CAC, long-term CV mortality was similar (P = 0.67), whereas detectable CAC was associated with 1.3-higher hazard for CV death among women when compared with men (P < 0001). Cardiovascular mortality was higher among women with more extensive, numerous, or larger CAC lesions. The relative hazard for cardiovascular disease (CVD) mortality for women and men was 8.2 vs. 5.1 for multivessel CAC, 8.6 vs. 5.9 for ≥5 CAC lesions, and 8.5 vs. 4.4 for a lesion size ≥15 mm3, respectively. Additional explorations revealed that women with larger sized and more numerous CAC lesions had 2.2-fold higher CVD mortality (P < 0.0001) as compared to men. Moreover, CAC density was not predictive of CV mortality in women (P = 0.51) but was for men (P < 0.001), when controlling for CAC volume and cardiac risk factors. Conclusion: Our overall findings support that measures beyond the Agatston score provide important clues to sex differences in atherosclerotic plaque and may further refine risk detection and focus preventive strategies of care.

Coronary Artery Calcium to Guide a Personalized Risk-Based Approach to Initiation and Intensification of Antihypertensive Therapy.

BACKGROUND: The use of atherosclerotic cardiovascular disease (ASCVD) risk to personalize systolic blood pressure (SBP) treatment goals is a topic of increasing interest. Therefore, we studied whether coronary artery calcium (CAC) can further guide the allocation of anti-hypertensive treatment intensity. METHODS: We included 3733 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with SBP between 120 and 179 mm Hg. Within subgroups categorized by both SBP (120-139 mm Hg, 140-159 mm Hg, and 160-179 mm Hg) and estimated 10-year ASCVD risk (using the American College of Cardiology/American Heart Assocation pooled-cohort equations), we compared multivariable-adjusted hazard ratios for the composite outcome of incident ASCVD or heart failure after further stratifying by CAC (0, 1-100, or >100). We estimated 10-year number-needed-to-treat for an intensive SBP goal of 120 mm Hg by applying the treatment benefit recorded in meta-analyses to event rates within CAC strata. RESULTS: The mean age was 65 years, and 642 composite events took place over a median of 10.2 years. In persons with SBP <160 mm Hg, CAC stratified risk for events. For example, among those with an ASCVD risk of <15% and who had an SBP of either 120 to 139 mm Hg or 140 to 159 mm Hg, respectively, we found increasing hazard ratios for events with CAC 1 to 100 (1.7 [95% confidence interval, 1.0-2.6] or 2.0 [1.1-3.8]) and CAC >100 (3.0 [1.8-5.0] or 5.7 [2.9-11.0]), all relative to CAC=0. There appeared to be no statistical association between CAC and events when SBP was 160 to 179 mm Hg, irrespective of ASCVD risk level. Estimated 10-year number-needed-to-treat for a SBP goal of 120mmHg varied substantially according to CAC levels when predicted ASCVD risk <15% and SBP <160mmHg (eg, 10-year number-needed-to-treat of 99 for CAC=0 and 24 for CAC>100, when SBP 120-139mm Hg). However, few participants with ASCVD risk <5% had elevated CAC. Furthermore, 10-year number-needed-to-treat estimates were consistently low and varied less among CAC strata when SBP was 160 to 179 mm Hg or when ASCVD risk was ≥15% at any SBP level. CONCLUSIONS: Combined CAC imaging and assessment of global ASCVD risk has the potential to guide personalized SBP goals (eg, choosing a traditional goal of 140 or a more intensive goal of 120 mm Hg), particularly among adults with an estimated ASCVD risk of 5% to 15% and prehypertension or mild hypertension.

Role of Coronary Artery Calcium Score of Zero and Other Negative Risk Markers for Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Limited attention has been paid to negative cardiovascular disease (CVD) risk markers despite their potential to improve medical decision making. We compared 13 negative risk markers using diagnostic likelihood ratios (DLRs), which model the change in risk for an individual after the result of an additional test. METHODS AND RESULTS: We examined 6814 participants from the Multi-Ethnic Study of Atherosclerosis. Coronary artery calcium score of 0, carotid intima-media thickness <25th percentile, absence of carotid plaque, brachial flow-mediated dilation >5% change, ankle-brachial index >0.9 and <1.3, high-sensitivity C-reactive protein <2 mg/L, homocysteine <10 µmol/L, N-terminal pro-brain natriuretic peptide <100 pg/mL, no microalbuminuria, no family history of coronary heart disease (any/premature), absence of metabolic syndrome, and healthy lifestyle were compared for all and hard coronary heart disease and all CVD events over the 10-year follow-up. Models were adjusted for traditional CVD risk factors. Among all negative risk markers, coronary artery calcium score of 0 was the strongest, with an adjusted mean DLR of 0.41 (SD, 0.12) for all coronary heart disease and 0.54 (SD, 0.12) for CVD, followed by carotid intima-media thickness <25th percentile (DLR, 0.65 [SD, 0.04] and 0.75 [SD, 0.04], respectively). High-sensitivity C-reactive protein <2 mg/L and normal ankle-brachial index had DLRs >0.80. Among clinical features, absence of any family history of coronary heart disease was the strongest (DLRs, 0.76 [SD, 0.07] and 0.81 [SD, 0.06], respectively). Net reclassification improvement analyses yielded similar findings, with coronary artery calcium score of 0 resulting in the largest, most accurate downward risk reclassification. CONCLUSIONS: Negative results of atherosclerosis-imaging tests, particularly coronary artery calcium score of 0, resulted in the greatest downward shift in estimated CVD risk. These results may help guide discussions on the identification of individuals less likely to receive net benefit from lifelong preventive pharmacotherapy.

Prognostic Value of Pericardial Effusion on Serial Echocardiograms in Pulmonary Arterial Hypertension.

BACKGROUND: Pericardial effusion in pulmonary arterial hypertension (PAH) is an indicator of right heart failure and poor prognosis; its significance on serial transthoracic echocardiograms (TTE) is not clear. METHODS: Baseline and follow-up TTE (1.0 ± 0.5 years), clinical parameters, and outcomes were studied (N = 200) in consecutive patients with PAH who underwent TTE at our center between October 1999 and November 2007. Study baseline TTE was 2.8 ± 4.0 years from initial PAH diagnosis. RESULTS: Over median follow-up of 3.6 ± 2.6 years from baseline TTE, 106 patients (53%) died. Pericardial effusion was present in 20% at baseline, and at any time during the study in 29%. Patients with any pericardial effusion during follow-up were more likely to have underlying connective tissue disease. They also had significantly higher mean right atrial pressure and pulmonary vascular resistance, had lower cardiac output by invasive hemodynamic studies, had higher serum creatinine, and were more likely to be treated with prostanoids. Patients were also significantly likely to have more echocardiographic right atrial dilation and right ventricular dilation and dysfunction, and worse tricuspid regurgitation with higher peak velocity. During follow-up, there was significantly increased use of prostanoids (58% vs. 28%) and combination therapy (8% vs. 2%) compared to baseline. Persistence of pericardial effusion on both baseline and follow-up TTE was associated with worse outcome, and an independent predictor of survival after adjusting for age, creatinine, functional class, and hemodynamics (P < 0.01). CONCLUSION: Persistence of pericardial effusion in PAH despite vasoactive therapy predicts worse outcomes; absence or resolution of pericardial effusion with therapy suggests better prognosis.

The Association of Mitral Annular Calcification with Cardiovascular and Non-Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis.

Mitral annular calcification (MAC) may be a potential marker of biological aging. However, the association of MAC with non-cardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and non-cardiovascular mortality, is not well studied in a multiracial cohort. We used data from 6,814 participants (mean age:62.2±10.2 years; 52.9%-females) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with non-contrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed cross-sectional association of MAC with BMD and walking pace. Also, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. Additionally, we assessed the association of MAC with cardiovascular and non-cardiovascular mortality using competing risks regression. The prevalence of MAC was 9.5% and was higher in women (10.7%) than in men (8.0%). MAC was associated with low BMD (coefficient: -0.04; 95%CI: -0.06 - -0.02) with significant interaction by sex (p-interaction:0.035). MAC was, however, not associated with impaired walking pace (odds ratio:1.09; 95%CI:0.89-1.33). Compared to individuals without MAC, those with MAC had an increased risk of incident renal failure albeit nonsignificant (hazard ratio [HR]:1.18; 95%CI:0.95-1.45) but a significantly higher hazards of dementia (HR:1.36; 95%CI:1.10-1.70). Additionally, persons with MAC had a substantially higher risk of all-cause (HR:1.47; 95%CI:1.29-1.69), cardiovascular (sub-distribution HR:1.39; 95%CI:1.04-1.87), and non-cardiovascular mortality (sub-distribution HR:1.35; 95%CI:1.14-1.60), compared to those without MAC. MAC≥100 vs <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and non-cardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia, as well as all-cause, cardiovascular, and non-cardiovascular mortality in this multiracial cohort. Thus, MAC may be a marker not only for atherosclerotic burden but also for other metabolic and inflammatory factors that increase the risk of non-cardiovascular outcomes and death from other causes.

Carotid Ultrasound-Based Plaque Score for the Allocation of Aspirin for the Primary Prevention of Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis and the Atherosclerosis Risk in Communities Study.

BACKGROUND: Coronary artery calcium testing using noncontrast cardiac computed tomography is a guideline-indicated test to help refine eligibility for aspirin in primary prevention. However, access to cardiac computed tomography remains limited, with carotid ultrasound used much more often internationally. We sought to update the role of aspirin allocation in primary prevention as a function of subclinical carotid atherosclerosis. METHODS AND RESULTS: The study included 11 379 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) and ARIC (Atherosclerosis Risk in Communities) studies. A harmonized carotid plaque score (range, 0-6) was derived using the number of anatomic sites with plaque from the left and right common, bifurcation, and internal carotid artery on ultrasound. The 5-year number needed to treat and number needed to harm as a function of the carotid plaque score were calculated by applying a 12% relative risk reduction in atherosclerotic cardiovascular disease (ASCVD) events and 42% relative increase in major bleeding events related to aspirin use, respectively. The mean age was 57 years, 57% were women, 23% were Black, and the median 10-year ASCVD risk was 12.8%. The 5-year incidence rates (per 1000 person-years) were 5.5 (4.9-6.2) for ASCVD and 1.8 (1.5-2.2) for major bleeding events. The overall 5-year number needed to treat with aspirin was 306 but was 2-fold lower for individuals with carotid plaque versus those without carotid plaque (212 versus 448). The 5-year number needed to treat was less than the 5-year number needed to harm when the carotid plaque score was ≥2 for individuals with ASCVD risk 5% to 20%, whereas the presence of any carotid plaque demarcated a favorable risk-benefit for individuals with ASCVD risk >20%. CONCLUSIONS: Quantification of subclinical carotid atherosclerosis can help improve the allocation of aspirin therapy.

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.

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.

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.