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AimsWhether isolated diastolic hypertension (IDH), as defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline, is associated with cardiovascular disease (CVD) has been disputed. We aimed to further study the associations of IDH with (i) subclinical CVD in the form of coronary artery calcium (CAC), (ii) incident systolic hypertension, and (iii) CVD events.Methods and resultsWe used multivariable-adjusted logistic and Cox regression to test whether IDH by 2017 ACC/AHA criteria (i.e. systolic blood pressure 0 of 0.88 (95% CI 0.66, 1.17)]. Similarly, while IDH was associated with incident systolic hypertension, there was no statistically significant associations with incident CVD [hazard ratio 1.19 (95% CI 0.77, 1.84)] or death [hazard ratio 0.94 (95% CI 0.65, 1.36)] over 13 years in MESA. In a stratified meta-analysis of eight cohort studies (10 037 843 participants), the 2017 IDH definition was also not consistently associated with CVD and the relative magnitude of any potential association was noted to be numerically small [e.g. depending on inclusion criteria applied in the stratification, the adjusted hazard ratios ranged from 1.04 (95% CI 0.98, 1.10) to 1.09 (95% 1.03, 1.15)].ConclusionThe lack of consistent excess in CAC or CVD suggests that emphasis on healthy lifestyle rather than drug therapy is sufficient among the millions of middle-aged or older adults who now meet the 2017 ACC/AHA criteria for IDH, though they require follow-up for incident systolic hypertension. These findings may not extrapolate to adults younger than 40 years, motivating further study in this age group.

Background and aimsA large proportion of statin eligible candidates have a baseline absence of coronary artery calcium (CAC) and low 10-year atherosclerotic cardiovascular disease (ASCVD) risk. We sought to determine the proportion of statin eligible individuals who had long-term healthy arterial aging (persistent CAC = 0) and their examined 15-year ASCVD outcomes.MethodsWe included 561 statin eligible candidates from the Multi-Ethnic Study of Atherosclerosis who were not on statin therapy with CAC = 0 at Visit 1 (2000-02) and underwent a subsequent CAC scan at Visit 5 (2010-11). Adjusted Cox proportional hazards regression assessed the association between persistent CAC = 0 and ASCVD events over 15.9 years.ResultsParticipants were on average 61.7 years old, 50% were women, and 43% maintained long-term CAC = 0. Individuals with an LDL-C ≥190 mg/dL (54%) and those with an ASCVD risk ≥20% (33%) had the highest and lowest proportion of persistent CAC = 0, respectively. There were 57 ASCVD events, and 15-year ASCVD event rates were low for individuals with and without healthy arterial aging (4.3 versus 8.6 per 1,000 persons-years), but the 10-year number needed to treat to prevent one ASCVD event differed by more than two fold (117 versus 54). In multivariable modeling, persistent CAC = 0 conferred a 51% lower risk of ASCVD compared to those with incident CAC (HR = 0.49, 95% CI: 0.27-0.90, p=0.02).ConclusionsMore than 40% of statin eligible individuals with baseline CAC = 0 had long-term healthy arterial aging. Statin eligible candidates with persistent CAC = 0 had a very low 15-year ASCVD risk, suggesting that statin therapy may be of limited benefit among this group of individuals.

Untreated hypertension may contribute to increased atherosclerotic cardiovascular disease (ASCVD) risk in South Asians (SA). We assessed HTN prevalence among untreated adults free of baseline ASCVD from the MASALA & MESA studies. The proportion of participants who received discordant recommendations regarding antihypertensive pharmacotherapy use by the 2017-ACC/AHA and JNC7 Guidelines across CAC score categories in each race/ethnic group was calculated. Compared with untreated MESA participants (n = 3896), untreated SA (n = 445) were younger (55±8 versus 59±10 years), had higher DBP (73±10 versus 70±10 mmHg), total cholesterol (199±34 versus 196±34 mg/dL), statin use (16% versus 9%) and CAC=0 prevalence (69% versus 58%), with fewer current smokers (3% versus 15%) and lower 10-year-ASCVD-risk (6.4% versus 9.9%) (all p100 and thus may be better at informing hypertension management in American South Asians.

Knowing the patient's current cardiovascular disease (CVD) status, as well as the patient's current and future CVD risk, helps the clinician make more informed patient-centered management recommendations towards the goal of preventing future CVD events. Imaging tests that can assist the clinician with the diagnosis and prognosis of CVD include imaging studies of the heart and vascular system, as well as imaging studies of other body organs applicable to CVD risk. The American Society for Preventive Cardiology (ASPC) has published "Ten Things to Know About Ten Cardiovascular Disease Risk Factors." Similarly, this "ASPC Top Ten Imaging" summarizes ten things to know about ten imaging studies related to assessing CVD and CVD risk, listed in tabular form. The ten imaging studies herein include: (1) coronary artery calcium imaging (CAC), (2) coronary computed tomography angiography (CCTA), (3) cardiac ultrasound (echocardiography), (4) nuclear myocardial perfusion imaging (MPI), (5) cardiac magnetic resonance (CMR), (6) cardiac catheterization [with or without intravascular ultrasound (IVUS) or coronary optical coherence tomography (OCT)], (7) dual x-ray absorptiometry (DXA) body composition, (8) hepatic imaging [ultrasound of liver, vibration-controlled transient elastography (VCTE), CT, MRI proton density fat fraction (PDFF), magnetic resonance spectroscopy (MRS)], (9) peripheral artery / endothelial function imaging (e.g., carotid ultrasound, peripheral doppler imaging, ultrasound flow-mediated dilation, other tests of endothelial function and peripheral vascular imaging) and (10) images of other body organs applicable to preventive cardiology (brain, kidney, ovary). Many cardiologists perform cardiovascular-related imaging. Many non-cardiologists perform applicable non-cardiovascular imaging. Cardiologists and non-cardiologists alike may benefit from a working knowledge of imaging studies applicable to the diagnosis and prognosis of CVD and CVD risk - both important in preventive cardiology.

ObjectivesThis study sought to quantify and model conversion of a normal coronary artery calcium (CAC) scan to an abnormal CAC scan.BackgroundAlthough the absence of CAC is associated with excellent prognosis, progression to CAC >0 confers increased risk. The time interval for repeated scanning remains poorly defined.MethodsThis study included 3,116 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with baseline CAC = 0 and follow-up scans over 10 years after baseline. Prevalence of incident CAC, defined by thresholds of CAC >0, CAC >10, or CAC >100, was calculated and time to progression was derived from a Weibull parametric survival model. Warranty periods were modeled as a function of sex, race/ethnicity, cardiovascular risk, and desired yield of repeated CAC testing. Further analysis was performed of the proportion of coronary events occurring in participants with baseline CAC = 0 that preceded and followed repeated CAC testing at different time intervals.ResultsMean participants' age was 58 ± 9 years, with 63% women, and mean 10-year cardiovascular risk of 14%. Prevalence of CAC >0, CAC >10, and CAC >100 was 53%, 36%, and 8%, respectively, at 10 years. Using a 25% testing yield (number needed to scan [NNS] = 4), the estimated warranty period of CAC >0 varied from 3 to 7 years depending on sex and race/ethnicity. Approximately 15% of participants progressed to CAC >10 in 5 to 8 years, whereas 10-year progression to CAC >100 was rare. Presence of diabetes was associated with significantly shorter warranty period, whereas family history and smoking had small effects. A total of 19% of all 10-year coronary events occurred in CAC = 0 prior to performance of a subsequent scan at 3 to 5 years, whereas detection of new CAC >0 preceded 55% of future events and identified individuals at 3-fold higher risk of coronary events.ConclusionsIn a large population of individuals with baseline CAC = 0, study data provide a robust estimation of the CAC = 0 warranty period, considering progression to CAC >0, CAC >10, and CAC >100 and its impact on missed versus detectable 10-year coronary heart disease events. Beyond age, sex, race/ethnicity, diabetes also has a significant impact on the warranty period. The study suggests that evidence-based guidance would be to consider rescanning in 3 to 7 years depending on individual demographics and risk profile.

BackgroundThere 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.MethodsOur 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).ResultsCompared 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.ConclusionsIndividuals 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.

BackgroundAbsence of coronary artery calcium (CAC) identifies asymptomatic individuals at low cardiovascular disease risk. Carotid artery plaque is a marker of increased risk, but its association with cardiovascular risk and incident CAC in people without CAC is unclear.MethodsMulti-Ethnic Study of Atherosclerosis participants with CAC score of 0 at enrollment who also underwent carotid plaque measurement using B-mode ultrasonography were prospectively followed for incident coronary heart disease, stroke, and cardiovascular disease events, and CAC (score >0 on up to 3 serial computed tomography scans). The association of carotid plaque presence and plaque score (Ln[score+1]) at baseline with cardiovascular events and incident CAC was evaluated with Cox proportional hazards regression models adjusted for demographics, risk factors, and statin use.ResultsAmong these 2673 participants (58 years, 64% women, 34% White, 30% Black, 24% Hispanic, and 12% Chinese), carotid plaque at baseline was observed in 973 (36%) and the median plaque score (range, 1-12) among those with plaque was 1. A total of 79 coronary heart disease, 80 stroke, and 151 cardiovascular disease events were observed during 16.1 years of follow-up. Carotid plaque presence and plaque score were independently associated with coronary heart disease risk (HRs, 1.66 [95% CI, 1.04-2.66]; and 1.48 [95% CI, 1.01-2.17], respectively) but not with stroke and cardiovascular disease risk. A total of 973 (36.4%) participants developed CAC over the evaluation period (median 9.3 years). Carotid plaque presence and plaque score were independently associated with incident CAC (HRs, 1.34 [95% CI, 1.18-1.54]; and 1.37 [95% CI, 1.21-1.54]), respectively.ConclusionsThe presence and extent of carotid plaque are associated with long-term coronary heart disease risk and incident CAC among middle-aged asymptomatic individuals with an initial CAC score of 0.

ObjectivesThe aim of this study was to evaluate whether machine learning (ML) of noncontrast computed tomographic (CT) and clinical variables improves the prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) deaths compared with coronary artery calcium (CAC) Agatston scoring and clinical data.BackgroundThe CAC score provides a measure of the global burden of coronary atherosclerosis, and its long-term prognostic utility has been consistently shown to have incremental value over clinical risk assessment. However, current approaches fail to integrate all available CT and clinical variables for comprehensive risk assessment.MethodsThe study included data from 66,636 asymptomatic subjects (mean age 54 ± 11 years, 67% men) without established ASCVD undergoing CAC scanning and followed for cardiovascular disease (CVD) and CHD deaths at 10 years. Clinical risk assessment incorporated the ASCVD risk score. For ML, an ensemble boosting approach was used to fit a predictive classifier for outcomes, followed by automated feature selection using information gain ratio. The model-building process incorporated all available clinical and CT data, including the CAC score; the number, volume, and density of CAC plaques; and extracoronary scores; comprising a total of 77 variables. The overall proposed model (ML all) was evaluated using a 10-fold cross-validation framework on the population data and area under the curve (AUC) as metrics. The prediction performance was also compared with 2 traditional scores (ASCVD risk and CAC score) and 2 additional models that were trained using all the clinical data (ML clinical) and CT variables (ML CT).ResultsThe AUC by ML all (0.845) for predicting CVD death was superior compared with those obtained by ASCVD risk alone (0.821), CAC score alone (0.781), and ML CT alone (0.804) (p

ObjectivesThis study compared risk discrimination for the prediction of coronary heart disease (CHD) and cardiovascular disease (CVD) deaths for the Pooled Cohort Equations (PCE), the MESA (Multi-Ethnic Study of Atherosclerosis) Risk Score (with and without coronary artery calcium [CAC]), and of simple addition of CAC to the PCE.BackgroundThe PCE predict 10-year risk of atherosclerotic CVD events, and the MESA Risk Score predicts risk of CHD. Their comparative performance for the prediction of fatal events is poorly understood.MethodsWe evaluated 53,487 patients ages 45 to 79 years from the CAC Consortium, a retrospective cohort study of asymptomatic individuals referred for clinical CAC scoring. Risk discrimination was measured using C-statistics.ResultsMean age was 57 years, 35% were women, and 39% had CAC of 0. There were 421 CHD and 775 CVD deaths over a mean 12-year follow-up. In the overall study population, discrimination with the MESA Risk Score with CAC and the PCE was almost identical for both outcomes (C-statistics: 0.80 and 0.79 for CHD death, 0.77 and 0.78 for CVD death, respectively). Addition of CAC to the PCE improved risk discrimination, yielding the largest C-statistics. The MESA Risk Score with CAC and the PCE plus CAC showed the best discrimination among the 45% of patients with 5% to 20% estimated risk. Secondary analyses by estimated CVD risk strata showed modestly improved risk discrimination with CAC also among low- and high-estimated risk groups.ConclusionsOur findings support the current guideline recommendation to use, among available risk scores, the PCE for initial risk assessment and to use CAC for further risk assessment in a broad borderline and intermediate risk group. Also, in select individuals at low or high estimated risk, CAC modestly improved discrimination. Studies in unselected populations will lead to further understanding of the potential value of tools combining risk scores and CAC for optimal risk assessment.

Background and aimsSouth Asians (SA) experience disproportionately higher rates of atherosclerotic cardiovascular disease (ASCVD) events than non-Hispanic whites (NHW) and several other Asian groups. The coronary artery calcium (CAC) Agatston score may not capture the unique characteristics of coronary plaque in SA. We therefore evaluated the prevalence and patterns of advanced CAC measures (specific coronary vessel involvement, CAC volume and density) in SA versus other race/ethnicities.MethodsWe combined data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts. We used multivariable-adjusted linear regression models to compare advanced CAC measures between SA and other ethnicities.ResultsOur analyses included 7,625 individuals (810 SA, 2,622 whites, 1,893 African Americans, 1,496 Hispanics, 803 Chinese Americans) with mean (SD) age 62 (10) years and 48% men. In adjusted analyses, compared to NHW, SA had lower overall CAC volume [beta coefficient (95% CI)] [-0.46 (-0.62,-0.29)] but higher overall CAC density [0.14 (0.11,0.18)]. These trends were similar when SA were compared to non-whites (Hispanics, Chinese Americans, and African Americans). SA had higher overall [0.07 (0.03,0.12)] and right coronary artery [0.09 (0.03,0.16)] CAC density compared to non-whites, while CAC volume was not significantly different between these two groups.ConclusionsSA have lower CAC volume compared to NHW but similar compared to non-whites. Overall CAC density is higher among SA compared to NHW and non-whites. Future longitudinal studies of ASCVD events are required to confirm the prognostic significance of these findings among SA.

ObjectivesThe purpose of this study was to identify predictors of healthy arterial aging (long-term coronary artery calcification [CAC] of 0) among individuals with metabolic syndrome (MetS) or type 2 diabetes (T2D), which may improve primary prevention strategies.BackgroundIndividuals with MetS or T2D have a heterogeneously increased risk of atherosclerotic cardiovascular disease and not all have a high-intermediate risk.MethodsWe included 574 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with MetS or T2D who had CAC=0 at baseline and a repeat CAC scan 10 years later. Multivariable logistic regression assessed the association of traditional and novel atherosclerotic cardiovascular disease risk factors and the MetS severity score (based on the 5 MetS criteria) with healthy arterial aging.ResultsThe mean age of participants was 58.9 years, 67% were women, 422 participants had MetS, and 152 had T2D. The proportion with long-term CAC=0 was similar for MetS (42%) and T2D (44%). A younger age was the only individual low/normal traditional risk factor associated with an increased likelihood of long-term CAC=0 (odds ratio [OR]: 1.50; 95% confidence interval [CI]: 1.22 to 1.85 per 10-years younger). The strongest associations of nontraditional risk factors were observed for an absence of thoracic calcification (OR: 2.42; 95% CI: 1.24 to 4.72), absence of carotid plaque (OR: 1.81; 95% CI: 1.25 to 2.61), and among persons with a high sensitivity troponin

Background and aimsStatins do not decrease coronary artery calcium (CAC) and may increase existing calcification or its density. Therefore, we examined the prognostic significance of CAC among statin users at the time of CAC scanning.MethodsWe included 28,025 patients (6151 statin-users) aged 40-75 years from the CAC Consortium. Cox regression models were used to assess the association of CAC with coronary heart disease (CHD) and cardiovascular disease (CVD) mortality. Models were adjusted for traditional CVD risk factors. Additionally, we examined the predictive performance of CAC components including CAC area, volume, and density using an age- and sex-adjusted Cox regression model.ResultsParticipants (mean age 53.9 ± 10.3 years, 65.0% male) were followed for median 11.2 years. There were 395 CVD and 182 CHD deaths. One unit increase in log CAC score was associated with increased risk of CVD mortality (hazard ratio (HR), 1.2; 95% CI = 1.1-1.3) and CHD mortality (HR, 1.2; 95% CI = 1.1-1.4)) among statin users. There was a small but significant negative interaction between CAC score and statin use for the prediction of CHD (p-value = 0.036) and CVD mortality (p-value = 0.025). The volume score and CAC area were similarly associated with outcomes in statin users and non-users. Density was associated with CVD and CHD mortality in statin naïve patients, but with neither in statin users.ConclusionCAC scoring retains robust risk prediction in statin users, and the changing relationship of CAC density with outcomes may explain the slightly weaker relationship of CAC with outcomes in statin users.

BackgroundIdentifying cancer patients at high risk of CVD is important for targeting CVD prevention strategies and evaluating chemotherapy options in the context of cardiotoxicity. Coronary artery calcium (CAC), a strong marker of coronary atherosclerosis, is used clinically to enhance risk assessment, yet the value of CAC for assessing risk of CVD complications in cancer is poorly understood.ObjectiveIn cases of cancer mortality, to determine the value of CAC for predicting risk of CVD as a supporting cause of death.MethodsThe CAC Consortium is a multi-center cohort of 66,636 asymptomatic adults without CVD who underwent CAC scanning. During a follow-up of 12.5 years, 1129 patients died of cancer and were included in this analysis. The primary outcome was presence of CVD listed as a supporting cause of cancer mortality on official death certificates obtained from the National Death Index. Logistic regression models were used to assess the odds of CVD being listed as a supporting cause of death by CAC.ResultsCVD was listed as a supporting cause of death in 306 (27%) cancer mortality cases. Baseline CAC was significantly higher in individuals with CVD-supported mortality. Odds ratios of having CVD-supported death increased by ASCVD risk score category [1.15 (0.81, 1.65) for 5-20% 10-year risk and 1.97 (1.36, 2.89) for ≥20% risk, in reference to

BackgroundCoronary artery calcium (CAC) is a guideline recommended cardiovascular disease (CVD) risk stratification tool that increases with age and is associated with non-cardiovascular disease outcomes including cancer. We sought to define the age-specific change in the association between CAC and cause-specific mortality.MethodsThe Coronary Artery Calcium Consortium includes 59,502 asymptomatic patients age 40-75 without known CVD. Age-stratified mortality rates and parametric survival regression modeling was performed to estimate the age-specific CAC score at which CVD and cancer mortality risk were equal.ResultsThe mean age was 54±8 years (67% men) and there were 2,423 deaths over a mean 12±3 years follow-up. Among individuals with CAC = 0, cancer was the leading cause of death, with low CVD mortality rates for both younger (40-54 years) 0.2/1,000 person-years and older participants (65-75 years) 1.3/1,000 person-years. When CAC ≥400, CVD was consistently the leading cause of death among younger (71% of deaths) and older participants (56% of deaths). The CAC score at which CVD overtook cancer as the leading cause of death increased exponentially with age and was approximately 115 at age 50 and 380 at age 65.ConclusionsRegardless of age, when CAC = 0 cancer was the leading cause of death and the cardiovascular disease mortality rate was low. Our age-specific estimate for the CAC score at which CVD overtakes cancer mortality allows for a more precise approach to synergistic prediction and prevention strategies for CVD and cancer.

ObjectiveWhile diabetes has been previously noted to be a stronger risk factor for cardiovascular disease (CVD) in women compared with men, whether this is still the case is not clear. Coronary artery calcium (CAC) predicts coronary heart disease (CHD) and CVD in people with diabetes; however, its sex-specific impact is less defined. We compared the relation of CAC in women versus men with diabetes for total, CVD, and CHD mortality.Research design and methodsWe studied adults with diabetes from a large registry of patients with CAC scanning with mortality follow-up over 11.5 years. Cox regression examined the relation of CAC with mortality end points.ResultsAmong 4,503 adults with diabetes (32.5% women) aged 21-93 years, 61.2% of women and 80.4% of men had CAC >0. Total, CVD, and CHD mortality rates were directly related to CAC; women had higher total and CVD death rates than men when CAC >100. Age- and risk factor-adjusted hazard ratios (HRs) per log unit CAC were higher among women versus men for total mortality (1.28 vs. 1.18) (interaction P = 0.01) and CVD mortality (1.47 vs. 1.27) (interaction P = 0.04) but were similar for CHD mortality (1.48 and 1.48). For CVD mortality, HRs with CAC scores of 101-400 and >400 were 3.67 and 6.27, respectively, for women and 1.63 and 3.48, respectively, for men (interaction P = 0.04). For total mortality, HRs were 2.56 and 4.05 for women, respectively, and 1.88 and 2.66 for men, respectively (interaction P = 0.01).ConclusionsCAC predicts CHD, CVD, and all-cause mortality in patients with diabetes; however, greater CAC predicts CVD and total mortality more strongly in women.

BackgroundCoronary artery calcium (CAC) predicts atherosclerotic cardiovascular disease (ASCVD) events, inclusive of coronary heart disease (CHD) and stroke, and is a decision-making aid for primary prevention. The predictive value of CAC categories for CHD and stroke separately and across sex and race groups of an asymptomatic population is unclear.MethodsWhite, Black, and Hispanic participants of MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) underwent CAC measurement at enrollment and were followed for incident ASCVD events. Ten-year CHD-to-stroke incidence ratios across CAC score categories 0, 1 to 99, and ≥100 were assessed. Associations of CAC with incident CHD and stroke events were evaluated using multivariable-adjusted Cox models and multiplicative interactions of CAC with sex/race were tested.ResultsAmong 7042 participants (mean age, 57 years, 54% women, 36% Black, 23% Hispanic, 49% CAC=0, 19% CAC ≥100), 574 incident ASCVD events (333 CHD and 241 stroke) were observed over 12.3-year follow-up. Ten-year CHD-to-stroke incidence ratio increased significantly across CAC categories in men, women, Whites, Blacks, and Hispanics (all P

BackgroundRecent 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.MethodsThe 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: 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.ResultsOnly 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

ObjectivesThis 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.BackgroundAlthough CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate.MethodsThe 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.ResultsDuring 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.ConclusionsAcross 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.

BackgroundThe purpose of this study is to determine if a new score calculated with coronary artery calcium (CAC) density and volume is associated with total coronary artery plaque burden and composition on coronary CT angiography (CCTA) compared to the Agatston score (AS).MethodsWe identified 347 men enrolled in the Multicenter AIDS cohort study who underwent contrast and non-contrast CCTs, and had CAC>0. CAC densities (mean Hounsfield Units [HU]) per plaque) and volumes on non-contrast CCT were measured. A Density-Volume Calcium score was calculated by multiplying the plaque volume by a factor based on the mean HU of the plaque (4, 3, 2 and 1 for 130-199, 200-299, 300-399, and ≥400HU). Total Density-Volume Calcium score was determined by the sum of these individual scores. The semi-quantitative partially calcified and total plaque scores (PCPS and TPS) on CCTA were calculated. The associations between Density-Volume Calcium score, PCPS and TPS were examined.ResultsOverall, 2879 CAC plaques were assessed. Multivariable linear regression models demonstrated a stronger association between the log Density-Volume Calcium score and both the PCPS (β 0.99, 95%CI 0.80-1.19) and TPS (β 2.15, 95%CI 1.88-2.42) compared to the log of AS (PCPS: β 0.77, 95%CI 0.61-0.94; TPS: β 1.70, 95%CI 1.48-1.94). Similar results were observed for numbers of PC or TP segments.ConclusionThe new CAC score weighted towards lower density demonstrated improved correlation with semi-quantitative PC and TP burden on CCTA compared to the traditional AS, which suggests it has utility as an alternative measure of atherosclerotic burden.

Background and aimsWe sought to understand the risk factor correlates of very early coronary artery calcium (CAC), and the potential investigational value of CAC phenotyping in adults aged 20-30 years.MethodsWe studied all participants aged 20-30 years at baseline (N = 373) in the Coronary Artery Calcium Consortium, a large multi-center cohort study of patients aged 18 years or older without known atherosclerotic cardiovascular disease (ASCVD) at baseline, referred for CAC scoring for clinical risk stratification. We described the prevalence of CAC in men and women, the frequency of risk factors by the presence of CAC (CAC = 0 vs CAC >0), and assessed the association between traditional non-demographic CVD risk factors (hypertension, hyperlipidemia, smoking, family history of CHD, and diabetes) and prevalent CAC, using age- and sex-adjusted logistic regression models.ResultsThe mean age of the study participants was 27.5 ± 2.4 years; 324 (86.9%) had CAC = 0, and 49 (13.1%) had CAC >0. Among the 49 participants with CAC, 38 (77.6%) were men, and median CAC score was low at 4.6. In age- and sex-adjusted models, there was a graded increase in the odds of CAC >0 with increasing traditional cardiovascular disease (CVD) risk factor burden (p = 0.001 for linear trend). Participants with ≥3 traditional risk factors had a statistically significant higher odds of having prevalent CAC (OR 5.57, 95% CI; 1.82-17.03) compared to participants with no risk factors.ConclusionsOur study demonstrates the non-negligible prevalence of CAC among very high-risk young US adults, reinforcing the critical importance of traditional risk factors in the earliest development of detectable subclinical ASCVD.

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 and aimsThe long-term associations between zero, minimal coronary artery calcium (CAC) and cause-specific mortality are currently unknown, particularly after accounting for competing risks with other causes of death.MethodsWe evaluated 66,363 individuals from the CAC Consortium (mean age 54 years, 33% women), a multi-center, retrospective cohort study of asymptomatic individuals undergoing CAC scoring for clinical risk assessment. Baseline evaluations occurred between 1991 and 2010.ResultsOver a mean of 12 years of follow-up, individuals with CAC = 0 (45% prevalence, mean age 45 years) had stable low rates of coronary heart disease (CHD) death, cardiovascular disease (CVD) death (ranging 0.32 to 0.43 per 1000 person-years), and all-cause death (1.38-1.62 per 1000 person-years). Cancer was the predominant cause of death in this group, yet rates were also very low (0.47-0.79 per 1000 person-years). Compared to CAC = 0, individuals with CAC 1-10 had an increased multivariable-adjusted risk of CVD death only under age 40. Individuals with CAC>10 had multivariable-adjusted increased risks of CHD death, CVD death and all-cause death at all ages, and a higher proportion of CVD deaths.ConclusionsCAC = 0 is a frequent finding among individuals undergoing CAC scanning for risk assessment and is associated with low rates of all-cause death at 12 years of follow-up. Our results support the emerging consensus that CAC = 0 represents a unique population with favorable all-cause prognosis who may be considered for more flexible treatment goals in primary prevention. Detection of any CAC in young adults could be used to trigger aggressive preventive interventions.

BackgroundThe 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.MethodsWe 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.ResultsThe 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

ObjectivesThis 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.BackgroundCAC 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.MethodsA 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.ResultsThere 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.ConclusionsPatients 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.