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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. [ABSTRACT FROM AUTHOR]

Background: Coronary artery calcium (CAC) is heterogeneous in older age and is incompletely explained by traditional atherosclerotic cardiovascular disease risk factors. The extremes of subclinical atherosclerosis burden are strongly associated with either a low or high 10-year risk of incident atherosclerotic cardiovascular disease, respectively. However, the genetic underpinnings of differences in arterial aging remain unclear. We sought to determine the independent association of 2 polygenic scores for coronary heart disease (CHD) with CAC in adults ≥75 years of age., Methods: There were 1865 ARIC (Atherosclerosis Risk in Communities) participants who underwent genetic testing at visit 1 (1987-1989) and CAC scans at visit 7 (2018-2019). In the primary analysis, an externally derived multi-ancestry polygenic CHD risk score was calculated for both White and Black participants. Results were confirmed using a separate ARIC-derived polygenic CHD risk score, including ≥6 million variants computed for White participants. We used multivariable logistic regression models to assess the association of polygenic CHD risk with CAC, after adjusting for baseline, time-averaged lifestyle, traditional risk factors, and local ancestry principal components., Results: In the primary analysis, the average age was 80.6 years old, 61.6% were women, and the median CAC score was 246 (189 participants with CAC=0, 364 participants with CAC≥1000). Compared with persons below the 20th percentile of polygenic CHD risk, persons with polygenic-CHD risk above the 80th percentile had 82% lower odds of having CAC=0 (odds ratio, 0.18 [95% CI, 0.09-0.37]) and had >4-fold higher odds of CAC≥1000 (odds ratio, 4.77 [95% CI, 2.88-7.88]). On a continuous scale, each SD increment increase in the polygenic risk score was associated with a 78% higher CAC score. Results were nearly identical using a second confirmatory polygenic CHD risk score in White participants., Conclusions: Polygenic CHD risk is robustly associated with a lower prevalence of CAC=0 and a higher prevalence of CAC≥1000 in adults ≥75 years of age, beyond lifestyle and traditional risk factors. These results suggest a heritable contribution to distinct healthy and unhealthy arterial aging phenotypes that persist throughout the life course., Competing Interests: Dr Blaha reports grants from the National Institutes of Health, US Food and Drug Administration, American Heart Association, Amgen, Novo Nordisk, and Bayer, as well as Advisory Boards for Amgen, Novartis, Novo Nordisk, Bayer, Roche, Merck, Astra Zeneca, Eli Lilly, Boehringer Ingelheim, Vectura, Agepha. The other authors report no conflicts.

Mitral annular calcification (MAC) may be a potential marker of biologic aging. However, the association of MAC with noncardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and noncardiovascular 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% women) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with noncontrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed the cross-sectional association of MAC with BMD and walking pace. Furthermore, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. In addition, we assessed the association of MAC with cardiovascular and noncardiovascular 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% confidence interval [CI] -0.06 to -0.02), with significant interaction by gender (p-interaction = 0.035). MAC was, however, not associated with impaired walking pace (odds ratio 1.09, 95% CI 0.89 to 1.33). Compared with participants without MAC, those with MAC had an increased risk of incident renal failure, albeit nonsignificant (hazard ratio [HR] 1.18, 95% CI 0.95 to 1.45), and a significantly higher hazards of dementia (HR 1.36, 95% CI 1.10 to 1.70). In addition, participants with MAC had a substantially higher risk of all-cause (HR 1.47, 95% CI 1.29 to 1.69), cardiovascular (subdistribution HR 1.39, 95% CI 1.04 to 1.87), and noncardiovascular mortality (subdistribution HR 1.35, 95% CI 1.14 to 1.60) than those without MAC. MAC ≥100 versus <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and noncardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia and all-cause, cardiovascular, and noncardiovascular 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 noncardiovascular outcomes and death from other causes., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael J. Blaha has grants funded by NIH, FDA, AHA, Bayer, Novo Nordisk, Amgen. He is on advisory boards for Amgen, Novartis, Novo Nordisk, Bayer, Roche, Inozyme, Kaleido, 89Bio; and consults for Emocha health and Kowa. The other authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Funding Support and Author Disclosures The ARIC study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, 75N92022D00005). The MESA was supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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, &gt;300) will place a patient above the 75th percentile. Also, we derived gender-specific age cutoffs by which 95% of participants with any (&gt;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 &gt;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 (&gt;100) place nearly all men &lt;60 years and all women &lt;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 &lt;50 years and women &lt;60 years with any CAC, men &lt;60 years and women &lt;70 years with CAC &gt;100) for identifying CAC &gt;75th percentile that might be readily adopted in clinical practice., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The long-term prognostic significance of a coronary artery calcium (CAC) score of 0 is poorly defined in younger adults. We evaluated this among participants aged 45 to 55 years from the Multi-Ethnic Study of Atherosclerosis, and assessed whether additional biomarkers can identify subgroups at increased absolute risk. We included 1,407 participants (61% women) without diabetes or severe hypercholesterolemia, with estimated 10-year risk <20% and CAC = 0. We evaluated all and hard cardiovascular disease (CVD) events, overall and among subjects with each of the following: high-sensitivity C-reactive protein levels ≥2 mg/L, homocysteine ≥10 µmol/L, high-sensitivity cardiac troponin T ≥95th percentile, lipoprotein (a) >50 mg/dl, triglycerides ≥175 mg/dl, apolipoprotein B ≥130 mg/dl, albuminuria, thoracic aortic calcium, aortic valve calcium (AVC), mitral annular calcium, ankle-brachial index <0.9, any carotid plaque, and maximum internal carotid artery intima-media thickness (ICA-IMT) ≥1.5 mm. Median follow-up was 16 years, and overall CVD event rates were low (4% at 15 years). For most exposures evaluated, rates of all CVD events were <6 per 1,000 person-years, except for ICA-IMT ≥1.5 mm (6.43) and AVC (13.8). The number needed to screen to detect ICA-IMT ≥1.5 mm was 8, and 84 for AVC. Among participants with borderline/intermediate risk or premature family history, hard CVD event rates were <7 per 1,000 for most exposures, except for ICA-IMT ≥1.5 mm (8.25), albuminuria (8.30), and AVC (13.47). Nonsmokers and those with ICA-IMT <1.5 mm had very low rates. In conclusion, our results demonstrate a favorable long-term prognosis of CAC = 0 among adults aged ≤55 years, particularly among nonsmokers. ICA-IMT testing could be considered for further risk assessment in adults ≤55 years with CAC = 0 and uncertain management., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background Randomized trials of pharmacologic strength omega-3 fatty acid (n3-FA)-based therapies suggest a dose-dependent cardiovascular benefit. Whether blood n3-FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3-FA levels would be associated with incident bleeding and AF events in MESA (Multi-Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline. Methods and Results We examined the association between baseline plasma n3-FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization International Classification of Diseases, Ninth Revision ( ICD-9 ), and International Classification of Diseases, Tenth Revision ( ICD-10 ), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3-FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA. Conclusions In MESA, higher plasma levels of n3-FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.

Background The optimal method for communicating coronary heart disease (CHD) risk to individual patients is not yet clear. Recent research supports the concept of "coronary age" for more effective risk communication. We defined an individual's coronary age as the age at which an average healthy individual would have an equivalent estimated CHD risk as that calculated for the index individual, building on our previously validated MESA (Multi-Ethnic Study of Atherosclerosis) 10-year CHD Risk Score equations with and without coronary artery calcium (CAC). Methods and Results We derived a coronary age by (1) calculating the MESA 10-year CHD risk; (2) mathematically setting this equal to an equation describing risk of an average healthy MESA participant, as a function of age; and (3) solving for age. The risk discrimination of the resultant coronary age was compared with that of chronological age, the MESA CHD Risk Score, and CAC alone. Approximately 95% of coronary age values ranged from 30 years less to 30 years higher than chronological age. Although the mean chronological age of individuals experiencing CHD events compared with those free of events was 67.4 versus 61.8 years, the difference in coronary age including CAC was larger (80.6 versus 62.8 years). Coronary age with CAC had identical predictive ability to that of MESA CHD Risk Score and outperformed chronological age and CAC alone. Conclusions The newly derived coronary age is a convenient transformation of MESA CHD Risk, retaining very good risk discrimination. This easy-to-communicate tool will be available for patients and clinicians, potentially facilitating risk communication in routine care.

Background: Obesity is associated with higher risk for coronary artery calcium (CAC), but the relationship between body mass index (BMI) and mortality is complex and frequently paradoxical., Methods: We analyzed BMI, CAC, and subsequent mortality using data from the CAC Consortium, a multi-centered cohort of individuals free of established cardiovascular disease (CVD) who underwent CAC testing. Mortality was assessed through linkage to the Social Security Death Index and cause of death from the National Death Index. Multivariable logistic regression was used to determine odds ratios for the association of clinically relevant BMI categories and prevalent CAC. Cox proportional hazards regression modeling was used to determine hazard ratios for coronary heart disease, CVD, and all-cause mortality according to categories of BMI and CAC., Results: Our sample included 36 509 individuals, mean age 54.1 (10.3) years, 34.4% female, median BMI 26.6 (interquartile range, 24.1-30.1), 46.6% had zero CAC, and 10.5% had CAC ≥400. Compared with individuals with normal BMI, the multivariable adjusted odds of CAC >0 were increased in those overweight (odds ratio, 1.13 [95% CI, 1.1-1.2]) and obese (odds ratio, 1.5 [95% CI, 1.4-1.6]). Over a median follow-up of 11.4 years, there were 1550 deaths (4.3%). Compared with normal BMI, obese individuals had a higher risk of coronary heart disease, CVD, and all-cause mortality while overweight individuals, despite a higher odds of CAC, showed no significant increase in mortality. In a sex-stratified analysis, the increase in coronary heart disease, CVD, and all-cause mortality in obese individuals appeared largely limited to men, and there was a lower risk of all-cause mortality in overweight women (hazard ratio, 0.79 [95% CI, 0.63-0.98])., Conclusions: In a large sample undergoing CAC scoring, obesity was associated with a higher risk of CAC and subsequent coronary heart disease, CVD, and all-cause mortality. However, overweight individuals did not have a higher risk of mortality despite a higher risk for CAC.

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 (NNT 5 ) calculations, and a 42% relative risk increase in major bleeding events was used for the 5-year number needed to harm (NNH 5 ) 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 NNT 5 with aspirin to prevent 1 cardiovascular disease event was 476 and the NNH 5 was 355. The NNT 5 was also greater than or similar to the NNH 5 among estimated ASCVD risk strata. Conversely, CAC≥100 and CAC≥400 identified subgroups in which NNT 5 was lower than NNH 5 . This was true both overall (for CAC≥100, NNT 5 =140 versus NNH 5 =518) and within ASCVD risk strata. Also, CAC=0 identified subgroups in which the NNT 5 was much higher than the NNH 5 (overall, NNT 5 =1190 versus NNH 5 =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.

Objectives: This study sought to evaluate the association and burden of coronary artery calcium (CAC) with long-term, cause-specific mortality across the spectrum of baseline risk., Background: Although CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate., Methods: The CAC Consortium cohort is a multicenter cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC testing. The following risk factors (RFs) were considered: 1) current cigarette smoking; 2) dyslipidemia; 3) diabetes mellitus; 4) hypertension; and 5) family history of CHD., Results: During the 12.5-years median follow-up, 3,158 (4.7%) deaths occurred; 32% were cardiovascular disease (CVD) deaths. Participants with CAC scores ≥400 had a significantly increased risk for CHD and CVD mortality (hazard ratio [HR]: 5.44; 95% confidence interval [CI]: 3.88 to 7.62; and HR: 4.15; 95% CI: 3.29 to 5.22, respectively) compared with CAC of 0. Participants with ≥3 RFs had a smaller increased risk for CHD and CVD mortality (HR: 2.09; 95% CI: 1.52 to 2.85; and HR: 1.84; 95% CI: 1.46 to 2.31, respectively) compared with those without RFs. Across RF strata, CAC added prognostic information. For example, participants without RFs but with CAC ≥400 had significantly higher all-cause, non-CVD, CVD, and CHD mortality rates compared with participants with ≥3 RFs and CAC of 0., Conclusions: Across the spectrum of RF burden, a higher CAC score was strongly associated with long-term, all-cause mortality and a greater proportion of deaths due to CVD and CHD. Absence of CAC identified people with a low risk over 12 years of follow-up, with most deaths being non-CVD in nature, regardless of RF burden., (Copyright © 2020. Published by Elsevier Inc.)

Background Coronary artery calcium (CAC) is a predictor for the development of cardiovascular disease (CVD) and to a lesser extent cancer. The age- and sex-specific relationship of CAC with CVD and cancer mortality is unknown. Methods and Results Asymptomatic patients aged 40 to 75 years old without known CVD were included from the CAC Consortium. We calculated sex-specific mortality rates per 1000 person-years' follow-up. Using parametric survival regression modeling, we determined the age- and sex-specific CAC score at which the risk of death from CVD and cancer were equal. Among the 59 502 patients included in this analysis, the mean age was 54.9 (±8.5) years, 34% were women, and 89% were white. There were 671 deaths attributable to CVD and 954 deaths attributable to cancer over a mean follow-up of 12±3 years. Among patients with CAC=0, cancer was the leading cause of death, the total mortality rate was low (women, 1.8; men, 1.5), and the CVD mortality rate was exceedingly low for women (0.3) and men (0.3). The age-specific CAC score at which the risk of CVD and cancer mortality were equal had a U-shaped relationship for women, while the relationship was exponential for men. Conclusions The age- and sex-specific relationship of CAC with CVD and cancer mortality differed significantly for women and men. Our age- and sex-specific CAC score provides a more precise estimate and further facilitates the use of CAC as a synergistic tool in strategies for the prediction and prevention of CVD and cancer mortality.

Background: The Coronary Artery Calcium Data and Reporting System (CAC-DRS), which takes into account the Agatston score category (A) and the number of calcified vessels (N) has not yet been validated in terms of its prognostic significance., Methods: We included 54,678 patients from the CAC Consortium, a large retrospective clinical cohort of asymptomatic individuals free of baseline cardiovascular disease (CVD). CAC-DRS groups were derived from routine, cardiac-gated CAC scans. Cox proportional hazards regression models, adjusted for traditional CVD risk factors, were used to assess the association between CAC-DRS groups and CHD, CVD, and all-cause mortality. CAC-DRS was then compared to CAC score groups and regional CAC distribution using area under the curve (AUC) analysis., Results: The study population had a mean age of 54.2 ± 10.7, 34.4% female, and mean ASCVD score 7.3% ± 9.0. Over a mean follow-up of 12 ± 4 years, a total of 2,469 deaths (including 398 CHD deaths and 762 CVD deaths) were recorded. There was a graded risk for CHD, CVD and all-cause mortality with increasing CAC-DRS groups ranging from an all-cause mortality rate of 1.2 per 1,000 person-years for A0 to 15.4 per 1,000 person-years for A3/N4. In multivariable-adjusted models, those with CAC-DRS A3/N4 had significantly higher risk for CHD mortality (HR 5.9 (95% CI 3.6-9.9), CVD mortality (HR4.0 (95% CI 2.8-5.7), and all-cause mortality a (HR 2.5 (95% CI 2.1-3.0) compared to CAC-DRS A0. CAC-DRS had higher AUC than CAC score groups (0.762 vs 0.754, P < 0.001) and CAC distribution (0.762 vs 0.748, P < 0.001)., Conclusion: The CAC-DRS system, combining the Agatston score and the number of vessels with CAC provides better stratification of risk for CHD, CVD, and all-cause death than the Agatston score alone. These prognostic data strongly support new SCCT guidelines recommending the use CAC-DRS scoring., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: This study thoroughly explored the demographic and imaging characteristics, as well as the all-cause and cause-specific mortality risks of patients with a coronary artery calcium (CAC) score ≥1,000 in the largest dataset of this population to date., Background: CAC is commonly used to quantify cardiovascular risk. Current guidelines classify a CAC score of >300 or 400 as the highest risk group, yet little is known about the potentially unique imaging characteristics and mortality risk in individuals with a CAC score ≥1,000., Methods: A total of 66,636 asymptomatic adults were included from the CAC consortium, a large retrospective multicenter clinical cohort. Mean patient follow-up was 12.3 ± 3.9 years for patients with cardiovascular disease (CVD), coronary heart disease (CHD), cancer, and all-cause mortality. Multivariate Cox proportional hazards regression models adjusted for age, sex, and conventional risk factors were used to assess the relative mortality hazard of individuals with CAC ≥1,000 compared with, first, a CAC reference of 0, and second, with patients with a CAC score of 400 to 999., Results: There were 2,869 patients with CAC ≥1,000 (86.3% male, mean 66.3 ± 9.7 years of age). Most patients with CAC ≥1,000 had 4-vessel CAC (mean: 3.5 ± 0.6 vessels) and had greater total CAC area, higher mean CAC density, and more extracoronary calcium (79% with thoracic artery calcium, 46% with aortic valve calcium, and 21% with mitral valve calcium) than those with CAC scores of 400 to 999. After full adjustment, those with CAC ≥1,000 had a 5.04- (95% confidence interval [CI]: 3.92 to 6.48), 6.79- (95% CI: 4.74 to 9.73), 1.55- (95% CI:1.23 to 1.95), and 2.89-fold (95% CI: 2.53 to 3.31) risk of CVD, CHD, cancer, and all-cause mortality, respectively, compared to those with CAC score of 0. The CAC ≥1,000 group had a 1.71- (95% CI: 1.41 to 2.08), 1.84- (95% CI: 1.43 to 2.36), 1.36- (95% CI:1.07 to 1.73), and 1.51-fold (95% CI: 1.33 to 1.70) increased risk of CVD, CHD, cancer, and all-cause mortality compared to those with CAC scores 400 to 999. Graphic analysis of CAC ≥1,000 patients revealed continued logarithmic increase in risk, with no clear evidence of a risk plateau., Conclusions: Patients with extensive CAC (CAC ≥1,000) represent a unique very high-risk phenotype with mortality outcomes commensurate with high-risk secondary prevention patients. Future guidelines should consider CAC ≥1,000 patients to be a distinct risk group who may benefit from the most aggressive preventive therapy., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery calcium (CAC) has been shown in multiple populations to predict atherosclerotic cardiovascular disease. However, its predictive value in Asian-Americans is poorly described., Patients and Methods: We studied 1621 asymptomatic Asian-Americans in the CAC Consortium, a large multicenter retrospective cohort. CAC was modeled in categorical (CAC = 0; CAC = 1-99; CAC = 100-399; CAC ≥ 400) and continuous [ln (CAC + 1)] forms. Participants were followed over a mean follow-up of 12 ± 4 years for coronary heart disease (CHD) death, cardiovascular disease (CVD) death, and all-cause mortality. The predictive value of CAC for individual outcomes was assessed using multivariable-adjusted Cox regression models adjusted for traditional cardiovascular risk factors and reported as hazard ratios (95% confidence interval)., Results: The mean (SD) age of the population was 54 (11.2) years and 64% were men. The mean 10-year atherosclerotic cardiovascular disease risk score was 8%. Approximately half had a CAC score of 0, whereas 22.5% had a CAC score of greater than 100. A total of 56 deaths (16 CVD and 8 CHD) were recorded, with no CVD or CHD deaths in the CAC = 0 group. We noted a significantly increased risk of CHD [hazard ratio (HR): 2.6 (1.5-4.3)] and CVD [HR: 2.3 (1.8-2.9)] mortality per unit increase in In (CAC + 1). Compared to those with CAC scores of 0, individuals with CAC scores of at least 400 had over a three-fold increased risk of all-cause mortality [HR: 3.3 (1.3-8.6)]., Conclusion: Although Asian-Americans are a relatively low-risk group, CAC strongly predicts CHD, CVD, and all-cause mortality beyond traditional risk factors. These findings may help address existing knowledge gaps in CVD risk prediction in Asian-Americans.

Cardiorespiratory fitness (CRF) is inversely associated with atherosclerotic cardiovascular disease (ASCVD) risk. It is unclear whether the prognostic value of CRF differs by baseline estimated ASCVD risk. We studied a retrospective cohort of patients without known heart failure or myocardial infarction (MI) who underwent treadmill stress testing. CRF was measured by metabolic equivalents of task (METs) and ASCVD risk was calculated using the Pooled Cohorts Equations. Multivariable-adjusted Cox regressions analyses examined the association between METs and incident all-cause mortality and MI outcomes stratified by baseline ASCVD risk. The C-index evaluated risk discrimination while net reclassification improvement evaluated reclassification with CRF added to the ASCVD risk score. Our study population consisted of 57,999 patients of mean age 53 (13) years, 49% women, 64% white, 29% black. Over a median follow-up 11 years (interquartile range 8 to 14 years) there were 6,670 (11%) deaths, while there were 1,757 (3.0%) MIs over a median follow-up of 6 years (interquartile range 3 to 8 years). Among patients with ASCVD risk ≥20%, those with METs ≥12 had a 77% lower risk of all-cause mortality (Hazard ratio 0.23 95% confidence interval = 0.20, 0.27) and 67% lower risk of MI (Hazard ratio 0.33 95% confidence interval = 0.24, 0.46) compared to METs <6. Similar results were obtained for those with ASCVD risk <5%. Addition of METs to ASCVD risk score improved the C-statistic from 0.778 to 0.798 for all-cause mortality and 0.726 to 0.733 for MI (both p <0.001). Addition of METs to ASCVD risk score significantly reclassified risk of all-cause mortality (p <0.001) but not MI (p = 0.052). In conclusion, CRF is inversely associated with risk of all-cause mortality and MI at all levels of ASCVD risk, and provides incremental risk discrimination and reclassification beyond the ASCVD risk score., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We studied the association between cigarette smoking and incident heart failure (HF) in a racially diverse US cohort. We included 6,792 participants from the Multi-Ethnic Study of Atherosclerosis with information on cigarette smoking at baseline, characterized by status, intensity, burden, and time since quitting. Adjudicated outcomes included total incident HF cases and HF stratified by ejection fraction (EF) into HF with reduced EF (HFrEF; EF ≤ 40%) and preserved EF (HFpEF; EF ≥ 50%). We used Cox proportional hazards models adjusted for traditional cardiovascular risk factors and accounted for competing risk of each HF type. Mean age was 62 ± 10 years; 53% were women, 61% were nonwhite, and 13% were current smokers. A total of 279 incident HF cases occurred over a median follow-up of 12.2 years. The incidence rates of HFrEF and HFpEF were 2.2 and 1.9 cases per 1000 person-years, respectively. Current smoking was associated with higher risk of HF compared with never smoking (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.36 to 3.09); this was similar for HFrEF (HR, 2.58; 95% CI, 1.27 to 5.25) and HFpEF (HR, 2.51; 95% CI, 1.15 to 5.49). Former smoking was not significantly associated with HF (HR, 1.17; 95% CI, 0.88 to 1.56). Smoking intensity, burden, and time since quitting did not provide additional information for HF risk after accounting for smoking status., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We examined the utility of coronary artery calcium (CAC) for cardiovascular risk stratification among hypertensive adults, including those fitting eligibility for SPRINT (Systolic Blood Pressure Intervention Trial). Additionally, we used CAC to identify hypertensive adults with cardiovascular disease (CVD) mortality rates equivalent to those observed in SPRINT who may, therefore, benefit from the most intensive blood pressure therapy. Our study population included 16 167 hypertensive patients from the CAC Consortium, among whom 6375 constituted a "SPRINT-like" population. We compared multivariable-adjusted hazard ratios of coronary heart disease and CVD deaths by CAC category (0, 1-99, 100-399, ≥400). Additionally, we generated a CAC-CVD mortality curve for patients aged >50 years to determine what CAC scores were associated with CVD death rates observed in SPRINT. Mean age was 58.1±10.6 years. During a mean follow-up of 11.6±3.6 years, there were 409 CVD deaths and 207 coronary heart disease deaths. Increasing CAC scores were associated with increased coronary heart disease and CVD mortality (coronary heart disease-CAC 100-399: hazard ratio [95% CI] 1.88 [1.04-3.40], CAC ≥400: 4.16 [2.34-7.39]; CVD-CAC 100-399: 1.93 [1.31-2.83], CAC ≥400: 3.51 [2.40-5.13]). A similar increased risk was observed across 10-year atherosclerotic CVD risk categories and in the SPRINT-like population. A CAC score of 220 (confidence range, 165-270) was associated with the CVD mortality rate observed in SPRINT. CAC risk stratifies adults with hypertension, including those who are SPRINT eligible. A CAC score of 220 can identify hypertensive adults with SPRINT-level CVD mortality risk and, therefore, may be reasonable for identifying candidates for aggressive blood pressure therapy.

Background: The Society of Cardiovascular Computed Tomography (SCCT) recommends consideration of coronary artery calcium (CAC) scoring among individuals with a family history (FH) of coronary heart disease (CHD) and atherosclerotic cardiovascular disease (ASCVD) risk <5%. No dedicated study has examined the prognostic significance of CAC scoring among this population., Methods: The CAC Consortium is a multi-center observational cohort study from four clinical centers linked to long-term follow-up for cause-specific mortality. All CAC scans were physician referred and performed in patients without a history of CHD. Our analysis includes 14,169 patients with ASCVD scores <5% and self-reported FH of CHD., Results: This cohort had a mean age of 48.1 (SD 7.4), was 91.3% white, 47.4% female, had an average ASCVD score of 2.3% (SD 1.3), and 59.4% had a CAC = 0. The event rate for all-cause mortality was 1.2 per 1000 person-years, 0.3 per 1000 person-years for CVD-specific mortality, and 0.2 per 1000 person-years for CHD-specific mortality. In multivariable Cox proportional hazard models, those with CAC>100 had a 2.2 (95% CI 1.5-3.3) higher risk of all-cause mortality, 4.3 (95% CI 1.9-9.5) times higher risk of CVD-specific mortality, and a 10.4 (95% CI 3.2-33.7) times higher risk of CHD-specific mortality compared to individuals with CAC = 0. The NNS to detect CAC >100 in this sample was 9., Conclusion: In otherwise low risk patients with FH of CHD, CAC>100 were associated with increased risk of all-cause and CHD mortality with event rates in a range that may benefit with preventive pharmacotherapy. These data strongly support new SCCT recommendations regarding testing of patients with a family history of CHD., (Copyright © 2019. Published by Elsevier Inc.)

Aims: Coronary artery calcium (CAC) is the strongest predictor of cardiovascular disease (CVD), yet is also associated with chronic non-CVD such as cancer. We performed this analysis in order to describe the association of CAC with CVD vs. cancer mortality., Methods and Results: The CAC Consortium is comprised of 66 636 scans performed in asymptomatic patients without known CVD. The mean age was 54 ± 11 years and 67% of participants were men. Cause of death was ascertained from death certificates. The association of CAC with cause-specific mortality was calculated using Fine and Gray sub-distribution hazard ratio (SHR) models, which account for competing causes of death. There were 3158 deaths over a median 12 ± 4 years follow-up (37% cancer and 32% CVD). Cancer was the leading cause of death when CAC = 0 (50%) with CVD overtaking cancer when baseline CAC >300. Compared to participants with CAC = 0, the SHR for CVD mortality was 1.44 [95% confidence interval (CI) 1.14-1.81], 2.26 (95% CI 1.76-2.90), and 3.68 (95% CI 2.90-4.67) for patients with CAC 1-99, 100-299, and ≥300, and the SHR for cancer was 1.04 (95% CI 0.88-1.23), 1.19 (95% CI 0.98-1.46), and 1.30 (95% CI 1.07-1.58)., Conclusion: Cancer was the leading cause of death for patients with baseline CAC = 0, whereas CVD overtook cancer above a threshold of CAC >300. These results argue for a focused approach for patients at the extremes of CAC scoring while suggesting that combined CVD and cancer primary prevention strategies for patients with intermediate CAC scores may significantly decrease mortality from the two leading causes of death., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Importance: The interplay of self-rated health (SRH), coronary artery calcium (CAC) scores, and cardiovascular risk is poorly described., Objectives: To assess the degree of correlation between SRH and CAC, to determine whether these measures are complementary for risk prediction, and to assess the incremental value of the addition of SRH to established risk tools., Design, Setting, and Participants: The Multi-Ethnic Study of Atherosclerosis (MESA) is a large population-based prospective cohort study of adults aged 45 to 84 years who were recruited from 6 US communities. A total of 6764 participants without baseline cardiovascular disease (CVD) were included in the analysis. Data were collected from July 2000 through August 2002. Follow-up was completed by December 2013, and data were analyzed from October 2018 to December 2018., Exposures: The EVGGFP (excellent, very good, good, fair, and poor) self-assessment of overall health (assessed before the baseline study examination) and CAC score. The EVGGFP rating was categorized as poor/fair, good, very good, or excellent., Main Outcomes and Measures: Hard coronary heart disease (CHD) events, hard CVD events, and all-cause mortality during a median follow-up of 13.2 years (interquartile range, 12.7-13.7 years)., Results: Among the study population of 6764 participants, the mean (SD) age was 62.1 (10.2) years, and 52.9% were women. The EVGGFP rating was strongly associated with age, sex, race/ethnicity, educational and income levels, healthy diet and physical activity, and cardiovascular risk factors. Despite encapsulating many risk variables, no correlation (r = -0.007; P = .57) or association between EVGGFP and the presence (χ2 = 0.84; P = .84) or severity (χ2 = 4.64; P = .86) of CAC was found. During follow-up, 1161 deaths, 637 hard CVD events, and 405 hard CHD events were recorded. In models adjusted for age, sex, race/ethnicity, and CAC, participants who reported excellent health had a 45% lower risk of CVD (hazard ratio [HR], 0.55; 95% CI, 0.39-0.77) and a 42% lower risk of CHD (HR, 0.58; 95% CI, 0.37-0.90) compared with those who reported poor/fair health. Participants in the excellent SRH category who had any CAC had markedly elevated risk of hard CHD (HR, 6.19; 95% CI, 2.1-18.3) and CVD (HR, 6.50; 95% CI, 2.7-15.6) events compared with those with a CAC score of 0. The addition of the EVGGFP rating to CAC improved the area under the curve (C statistic) for CHD events (0.725 vs 0.734; P = .007), CVD events (0.693 vs 0.706; P < .001), and all-cause mortality (0.685 vs 0.707; P < .001). However, the addition of the EVGGFP rating to the combination of CAC and atherosclerotic CVD risk score did not significantly improve C statistics for CHD events (0.751 vs 0.753; P = .39), CVD events (0.739 vs 0.741; P = .18), or all-cause mortality (0.779 vs 0.781; P = .13)., Conclusions and Relevance: Although SRH and CAC integrate many risk variables, this study suggests that they are poorly correlated and have complementary predictive utility. A perception of excellent health does not obviate the need for definitive assessment of CVD risk, whereas fair/poor perceived health may serve as a risk enhancer, arguing for advanced risk assessment in selected clinical scenarios.

Background and Aims: We aimed to evaluate the associations and prognostic value of interleukin-6 (IL6) for the prediction of atherosclerotic cardiovascular disease (ASCVD) events, heart failure (HF), and other chronic diseases in a large, multi-ethnic, contemporary population., Methods: We included 6617 participants from the Multi-Ethnic Study of Atherosclerosis (5640 non-users, 977 users of statins at baseline). Main outcomes were hard ASCVD events and HF; secondary outcomes included all-cause death, atrial fibrillation, venous thromboembolism and cancer., Results: Median follow-up was 13.2 years. Strong associations were observed in Cox regression analyses between higher IL6 levels and ASCVD events, HF, and mortality, particularly among statins users. In the latter, associations remained strong after adjusting for traditional risk factors and other inflammation biomarkers (e.g., risk factor, hsCRP-adjusted hazard ratio for incident HF comparing 3rd vs. 1st IL6 tertiles: 3.55, 95% CI 1.23-10.27). Although IL6 did not improve CHD prediction beyond traditional risk factors, among statin users it improved the prediction of stroke (improvement in the C statistic +0.018), incident HF (+0.028, the largest C statistic increase across all study outcomes), and all-cause death (+0.017)., Conclusions: IL6 is strongly and independently associated with ASCVD events, HF, and all-cause mortality, particularly among statin users. Although the prognostic value of IL6 is limited for the prediction of CHD events, it may have a role for the prediction of stroke, HF and all-cause death in asymptomatic statin users. Larger studies are needed to replicate these findings., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The prognostic value of hsCRP in contemporary multi-ethnic populations is unclear, particularly in statin users. The aim of this study was to characterize the prognostic utility of hsCRP for atherosclerotic CVD (ASCVD) risk prediction in a multi-ethnic population including non-users and users of statins followed for >13 years. Associations with heart failure (HF), atrial fibrillation (AF), venous thromboembolism (VTE), cancer, and all-cause death were also examined., Methods and Results: We evaluated 6757 participants from the Multi-Ethnic Study of Atherosclerosis (MESA; 1002 using statins at baseline), median follow-up 13.2 years. Higher levels of hsCRP were associated with a higher risk of all study endpoints in the unadjusted Cox Proportional Hazards regression analyses, except AF. Among non-users of statins, hsCRP only remained associated with VTE after adjusting for ASCVD risk factors, and did not improve risk prediction. Among users of statins, hsCRP did not improve ASCVD risk prediction either, although it was strongly associated with incident HF (HR for hsCRP ≥ 2 vs <2 mg/L 3.99; 95% CI 2.02, 7.90) and all-cause death (HR 1.52; 95% CI 1.11, 2.08) in multivariable analyses, and hsCRP significantly improved prediction of HF (area under the curve [AUC] basic model 0.741, AUC basic + hsCRP 0.788)., Conclusions: The utility of hsCRP for ASCVD prediction was modest. On the other hand, hsCRP was associated with incident VTE in statin non-users, and all-cause mortality and HF in statin users. In the latter, hsCRP improved the prediction of incident HF events. This finding should be replicated in larger cohorts., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The potential impact of the 2016 United States Preventive Services Task Force (USPSTF) guidelines on statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) warrants further analysis., Methods and Results: We studied participants from MESA (Multi-Ethnic Study of Atherosclerosis) aged 40 to 75 years and not on statins. We compared statin eligibility at baseline (2000-2002) and over follow-up between USPSTF and the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Coronary artery calcium (CAC) was measured at baseline. Absolute ASCVD event rates were calculated according to eligibility categories for each guideline. Among 4962 MESA participants (aged 59.3±8.8 years, 47.2% female), compared with ACC/AHA guidelines, baseline statin eligibility by USPSTF was significantly lower (34.4% versus 49.1%) and increased less over time (39.1% versus 59.1%) at examination 5 [years 2010-2012]). Compared with ACC/AHA, participants eligible by USPSTF were less likely to have zero CAC at baseline (36.6% versus 41.2%) and had higher rates of hard ASCVD events per 1000 person-years (11.6 [95% confidence interval, 10.2-13.3] versus 10.0 [8.9-11.3]). The hard ASCVD event rate in those eligible by ACC/AHA but not USPSTF was 6.5 (4.9-8.5) events per 1000 person-years, with the rate varying significantly according to baseline CAC (4.2 [2.7-6.7] events in those with CAC=0, 12.8 [8.3-19.9] events in those with CAC >100)., Conclusions: In MESA, compared with ACC/AHA, the USPSTF statin guidelines resulted in a 15% absolute decrease in eligibility. Participants with discordant eligibility had ASCVD rates that varied significantly according to baseline CAC, suggesting CAC could aid clinical decision making for statins in these individuals., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

We studied the association of coronary artery calcium (CAC) and risk of heart failure with preserved ejection fraction (HFpEF) among men and women in a multiethnic cohort. Coronary artery disease is a risk factor for development of HFpEF and assessment of subclinical atherosclerosis using CAC may allow for the early identification of patients at risk for HFpEF. We used data from the Multi-Ethnic Study of Atherosclerosis. CAC was measured at baseline in all participants. Incident HFpEF was defined as heart failure hospitalization with left ventricular ejection fraction ≥50%. Multivariable-adjusted Cox proportional hazards models were used to calculate HFpEF risk by CAC categories (0, 1 to 100, 101 to 300, and >300) and by CAC (continuous), stratified by gender and race/ethnicity. Of 6809 total participants, 127 incident HFpEF cases (1.8%) were ascertained. Mean age was 62 years (±10 years), and the participants were 53% female, 38% White, and 12% Black. In adjusted analysis, CAC >300 was associated with increased risk of HFpEF (hazard ratio [HR] 1.68, 95% confidence interval [95 CI] 1.00, 1.83); however, this was significant only in women (HR 2.82, 95% CI 1.32, 6.00 vs HR 0.91, 95% CI 0.46, 1.82 for men, interaction p = 0.03). Similarly, CAC modeled as a continuous variable was strongly predictive in women but not in men. In conclusion, measurement of CAC, a marker of coronary atherosclerosis, may stratify risk of HFpEF beyond traditional risk factors for women. Further investigation is needed to better understand potential gender differences in pathophysiology and presentation of HFpEF., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Given the aging population and prevalence of sedentary behaviour in the USA, we investigated the impact of differences in exercise capacity associated with age on long-term outcomes. We derived fitness-associated 'biologic age' as a tool to encourage positive lifestyle changes., Methods: This retrospective cohort study included 57085 patients without established coronary artery disease or heart failure (median age 53 years, 49% women, 29% black) who underwent clinically-referred treadmill stress testing at the Henry Ford Health System from 1991 to 2009. Patients were followed for 10.4±5 and 5.4±4 years for all-cause mortality and myocardial infarction (MI), respectively. We calculated hazard ratios associated with exercise capacity by age deciles using Cox regression models, adjusting for demographic and haemodynamic data, medical history, and medication use. Fitness-associated 'biologic age' was derived as the chronologic age with equivalent mortality or MI risk., Results: There were 6356 deaths and 1646 MIs during follow-up. Exercise capacity declined with increasing age. Higher exercise capacity was strongly associated with greater survival, with per-MET HR ranging from 0.82 (95% CI 0.78 to 0.86) in patients under 40 years of age, to 0.88 (95% CI 0.87 to 0.90) in those over 70 years of age. Biologic age varied markedly-up to three decades-within each age decile, and was a stronger predictor of mortality (C-statistic 0.81 vs 0.77) and MI (C-statistic 0.72 vs 0.68) than chronologic age., Conclusions: Higher exercise capacity remained a powerful predictor of survival despite lower average exercise capacity at older ages, reinforcing its importance in patients of all ages. Fitness-associated biologic age was a stronger predictor of survival than chronologic age, and may be a useful clinical tool for facilitating patient discussions regarding the impact of exercise capacity on long-term risk., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: The 2013 ACC/AHA Report on the Assessment of Cardiovascular (CVD) Risk redefined "intermediate risk". We sought to critically compare the intermediate risk groups identified by prior guidelines and the new ACC/AHA guidelines., Methods: We analyzed data from 30,005 adult men free of known CVD from a large, multi-ethnic study of middle-aged adults. The Framingham Risk Score was calculated using published equations, and CVD risk was calculated using the new ACC/AHA Pooled Cohort Equations Risk Estimator. We first compared the size and characteristics of the intermediate risk group identified by the old (ATP III, 10-20% 10-year CHD risk) and new guidelines (5-7.4% 10-year CVD risk). We then defined time-to-high-risk as the length of time an individual patient resides in the intermediate risk group before progressing to high risk status based on advancing age alone., Results: The mean age of the study population was 53 ± 13 years, and 24% were African-American. Patients identified as intermediate risk by the new ACC/AHA Guidelines were younger and more likely to be African-American and have lower risk factor burden (all p < 0.05). The new intermediate risk group was just 37% the size of the traditional ATP III intermediate risk group, while the new high risk group was 103% larger. Under the new guidelines, men remain intermediate risk for an average of just 3 years, compared to 8 years under the prior guidelines (63% shorter time-to-high-risk, p < 0.05), before progressing to high risk based on advancing age alone., Conclusion: The new 2013 ACC/AHA risk assessment guidelines produce a markedly smaller, lower absolute risk, and more temporary "intermediate risk" group. These findings reshape the modern understanding of "intermediate risk", and have distinct implications for risk assessment, clinical decision making, and pharmacotherapy in primary prevention., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)