Although the traditional Agatston coronary artery calcium (CAC) score is a powerful predictor of mortality, it is unknown if the regional distribution of CAC further improves cardiovascular risk prediction. We retrospectively studied 23,058 patients referred for Agatston CAC scoring, of whom 61% had CAC (n=14,084). CAC distribution was defined as the number of vessels with CAC (0 to 4, including left main). For multivessel CAC, "diffuse" CAC was defined by decreasing percentage of CAC in the single most affected vessel and by ≤75% total Agatston CAC score in the most calcified vessel. All-cause mortality was ascertained through the social security death index. The mean age was 55±11 years, with 69% men. There were 584 deaths (2.5%) over 6.6±1.7 years. Considerable heterogeneity existed between the Agatston CAC score group and the number of vessels with CAC. In each CAC group, increasing number of vessels with CAC was associated with an increased mortality rate. After adjusting for age, gender, Agatston CAC score, and cardiovascular risk factors, increasing number of vessels with CAC was associated with higher mortality risk compared with single-vessel CAC (2-vessel: HR 1.61 [95% CI 1.14 to 2.25], 3-vessel: 1.99 [1.44 to 2.77], and 4-vessel: 2.22 [1.53 to 3.23]). "Diffuse" CAC was associated with a higher mortality rate in the CAC 101 to 400 and >400 groups. Left main CAC was associated with increased mortality risk. In conclusion, increasing number of vessels with CAC and left main CAC predict increased all-cause mortality and improve the prognostic power of the traditional Agatston CAC score.

Background and aims

South Asians are at increased risk for cardiovascular disease (CVD). Aortic valve calcium (AVC) is associated with CVD risk and aortic stenosis. Elevated Lp(a) is a heritable risk factor for CVD and AVC. AVC prevalence and its association with Lp(a) have not been studied in South Asians.

Methods

Among participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study (n = 695), AVC prevalence and extent were compared to four race/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA) (n = 4671). Multivariable regression was performed to evaluate associations between Lp(a) and AVC stratified by race/ethnic groups, adjusting for cardiovascular risk factors.

Results

After age and sex adjustment, South Asians had higher median Lp(a) (17.0 mg/dL) compared to Whites (12.9 mg/dL), Hispanics (13.1 mg/dL) and Chinese Americans (12.9 mg/dL), and Blacks had highest Lp(a) levels (35.1 mg/dL). There were no differences in the odds of AVC in South Asians compared with Whites or Hispanics, after age and sex adjustment (p = 0.64 and 0.63, respectively). Odds of AVC was lower in Chinese (OR 0.35; 95%CI 0.23-0.54) and somewhat lower in Blacks compared with South Asians (OR 0.76; 0.56-1.04). There were no associations between Lp(a) and AVC presence or extent in South Asians. Lp(a) was associated with AVC only among Blacks and Whites.

Conclusions

Although present in Whites and Blacks, there were no associations between Lp(a) and AVC in South Asians. These differences may be due to statistic power or race specific modifying factors that influences the effect of Lp(a) particles on AVC pathogenesis.

Aims

Patients with a low lifetime risk of coronary heart disease (CHD) are not completely free of events over 10 years. We evaluated predictors for CHD among "low lifetime risk" participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA).

Methods

MESA enrolled 6814 men and women aged 45-84 years who were free of baseline cardiovascular disease. Using established criteria of non-diabetic, non-smokers with total cholesterol ≤ 200 mg/dL, systolic BP ≤ 139 mmHg, and diastolic BP ≤ 89 mmHg at baseline, we identified 1391 participants with a low lifetime risk for cardiovascular disease. Baseline covariates were age, gender, ethnicity, HDL-C, C-reactive protein, family history of CHD, carotid intima-media thickness and coronary artery calcium (CAC). We calculated event rates and the number needed to scan (NNS) to identify one participant with CAC>0 and > 100.

Results

Over 10.4 years median follow-up, there were 33 events (2.4%) in participants with low lifetime risk. There were 479 participants (34%) with CAC>0 including 183 (13%) with CAC>100. CAC was present in 25 (76%) participants who experienced an event. In multivariable analyses, only CAC>100 remained predictive of CHD (HR 4.6; 95% CI: 1.6-13.6; p = 0.005). The event rates for CAC = 0, CAC>0 and CAC>100 were 0.9/1,000, 5.7/1,000, and 11.0/1000 person-years, respectively. The NNS to identify one participant with CAC>0 and > 100 were 3 and 7.6, respectively.

Conclusions

While 10-year event rates were low in those with low lifetime risk, CAC was the strongest predictor of incident CHD. Identification of individuals with CAC = 0 and CAC>100 carries significant potential therapeutic implications.

Background

Absence 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.

Methods

Multi-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.

Results

Among 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.

Conclusions

The 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.

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 p<0.001). A higher proportion of untreated MASALA and MESA participants were diagnosed with hypertension and recommended anti-hypertensive pharmacotherapy according to the ACC/AHA guideline compared to JNC7 (all p<0.001). Overall, discordant BP treatment recommendations were observed in 9% SA, 11% Whites, 15% Blacks, 10% Hispanics, and 9% Chinese-American. In each race/ethnic group, the proportion of participants receiving discordant recommendation increased across CAC groups (all p<0.05), however was highest among SA (40% of participants). Similar to other race/ethnicities, a higher proportion of SA are recommended anti-hypertensive pharmacotherapy by ACC/AHA as compared with JNC7 guidelines. The increase was higher among those with CAC>100 and thus may be better at informing hypertension management in American South Asians.

Background

Coronary 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.

Methods

White, 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.

Results

Among 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<0.001). High CAC burden (score ≥100) was independently associated with ASCVD and CHD risk in all groups and with stroke risk in the overall cohort and Blacks. No sex- or race-based CAC interactions for ASCVD, CHD, and stroke events were observed. Adding CAC to a traditional risk factor model improved risk discrimination and reclassification for CHD but not for stroke events.

Conclusions

In 2 population-based cohorts of asymptomatic individuals, 10-year CHD-to-stroke incidence ratio was higher with increasing CAC score categories across sex and race groups, and CAC was consistently a better predictor of CHD than stroke. High CAC burden comparably associated with ASCVD risk across sex and race groups.

Background and aims

South Asian (SA) individuals are thought to represent a group that is at high-risk for atherosclerotic cardiovascular disease (ASCVD). However, the performance of the Pooled Cohort Equations (PCE) remains uncertain in SAs living in the US. We aimed to study the interplay between predicted 10-year ASCVD risk and coronary artery calcium (CAC) in SAs compared to other racial/ethnic groups.

Methods

We studied 536 SAs from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, and 2073 Non-Hispanic Whites (NHWs), 1514 African Americans (AAs), 1254 Hispanics, and 671 Chinese Americans (CAs) from the Multi-Ethnic Study of Atherosclerosis (MESA) who were not currently on statins. We used logistic regression models to assess the association between race/ethnicity and CAC within each ASCVD risk stratum.

Results

SAs at low and at intermediate estimated ASCVD risk were more likely to have CAC = 0 compared to NHWs, while SAs at high risk had a similar CAC burden to NHWs. For example, intermediate-risk SAs had a 73% higher odds of CAC = 0 compared to NHWs (95% 1.00-2.99), while high-risk SAs were equally likely to have CAC = 0 (OR 0.95, 95% CI 0.65-1.38) and CAC >100 (OR 0.86, 95% CI 0.61-1.22).

Conclusions

Our results suggest that the extent of ASCVD risk overestimation using the PCEs may be even greater among SAs considered at low and intermediate risk than among NHWs. Studies with incident ASCVD events are required to validate and/or recalibrate current ASCVD risk prediction tools in this group.

Background

There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations.

Methods

Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk).

Results

Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm²), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups.

Conclusions

Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.