Individuals of South Asian (SA) ancestry are predisposed to a higher risk of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC) volume and density can identify coronary plaque characteristics unique to SA that may provide important prognostic information to identify high risk individuals beyond traditional CAC scores. We used data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA). CAC density and volume were assessed according to established protocols. ASCVD risk was estimated using the pooled cohort equations (PCE). Multivariable-adjusted linear regression models were used to study the association between the PCE and advanced CAC measures, and between cardiovascular risk factors and CAC density and volume. Our analyses included 1,155 participants (mean age 57 (SD 9) years, 52% men) with information on advanced CAC measures. After multivariable-adjustment, the PCE was associated with both CAC density (β 0.24, 95% CI 0.12,0.35) and CAC volume (β 0.43, 95% CI 0.38,0.48). High-density lipoprotein cholesterol was directly associated with CAC density while waist circumference was inversely associated with it. Body mass index, hypertension status, statin use, diabetes, and HOMA-IR were all directly associated with CAC volume. Estimated ASCVD risk was associated with both CAC volume and density. Different cardiometabolic risk factors are associated with CAC density and volume. Future longitudinal studies are required to demonstrate the interrelationship of advanced CAC measures and cardiovascular risk factors with incident ASCVD outcomes.

Background and aims

South 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.

Methods

We 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.

Results

Our 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.

Conclusions

SA 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.

Introduction

We characterized the association of 3 metabolic conditions - obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) - with increased inflammation and subclinical atherosclerosis.

Methods

We conducted cross-sectional analysis of 3976 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with adequate CT imaging to diagnose NAFLD. Obesity was defined as BMI ≥ 30 kg/m(2), metabolic syndrome by AHA/NHLBI criteria, and NAFLD using non-contrast cardiac CT and a liver/spleen attenuation ratio (L/S) < 1. Increased inflammation was defined as high sensitivity C-reactive protein (hsCRP) ≥2 mg/L and subclinical atherosclerosis as coronary artery calcium (CAC) > 0. We studied the association of a stepwise increase in number of these metabolic conditions (0-3) with increased inflammation and CAC, stratifying results by gender and ethnicity.

Results

Mean age of participants was 63 (±10) years, 45% were male, 37% white, 10% Chinese, 30% African American, and 23% were Hispanic. Adjusting for obesity, metabolic syndrome and traditional risk factors, NAFLD was associated with a prevalence odds ratio for hsCRP ≥2 mg/L and CAC >0 of 1.47 (1.20-1.79) and 1.37 (1.11-1.68) respectively. There was a positive interaction between female gender and NAFLD in the association with hsCRP ≥2 mg/L (p = 0.006), with no interaction by race. With increasing number of metabolic conditions, there was a graded increase in prevalence odds ratios of hsCRP ≥2 mg/L and CAC >0.

Conclusion

NAFLD is associated with increased inflammation and CAC independent of traditional risk factors, obesity and metabolic syndrome. There is a graded association between obesity, metabolic syndrome, and NAFLD with inflammation and 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 (NNT₅) calculations, and a 42% relative risk increase in major bleeding events was used for the 5-year number needed to harm (NNH₅) estimations.

Results

Only 5% of MESA participants would qualify for aspirin consideration for primary prevention according to the American College of Cardiology/American Heart Association guidelines and using >20% estimated ASCVD risk to define higher risk. Benefit/harm calculations were restricted to aspirin-naive participants <70 years of age not at high risk of bleeding (n=3540). The overall NNT₅ with aspirin to prevent 1 cardiovascular disease event was 476 and the NNH₅ was 355. The NNT₅ was also greater than or similar to the NNH₅ among estimated ASCVD risk strata. Conversely, CAC≥100 and CAC≥400 identified subgroups in which NNT₅ was lower than NNH₅. This was true both overall (for CAC≥100, NNT₅=140 versus NNH₅=518) and within ASCVD risk strata. Also, CAC=0 identified subgroups in which the NNT₅ was much higher than the NNH₅ (overall, NNT₅=1190 versus NNH₅=567).

Conclusions

CAC may be superior to the pooled cohort equations to inform the allocation of aspirin in primary prevention. Implementation of current 2019 American College of Cardiology/American Heart Association guideline recommendations together with the use of CAC for further risk assessment may result in a more personalized, safer allocation of aspirin in primary prevention. Confirmation of these findings in experimental settings is needed.

Objectives

This 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.

Background

The 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.

Methods

We 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.

Results

Mean 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.

Conclusions

Our 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.

Aims

Whether 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 results

We used multivariable-adjusted logistic and Cox regression to test whether IDH by 2017 ACC/AHA criteria (i.e. systolic blood pressure <130 mmHg and diastolic blood pressure ≥80 mmHg) was associated with the above outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA). In a random-effects meta-analysis of the association between IDH and CVD events, we combined the MESA results with those from seven other previously published cohort studies. Among the 5104 MESA participants studied, 7.5% had IDH by the 2017 ACC/AHA criteria. There was no association between IDH and CAC [e.g. adjusted prevalence odds ratio for CAC >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)].

Conclusion

The 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

The prognostic value of coronary artery calcium (CAC) or carotid intima-media thickness (CIMT) among asymptomatic adults with a family history (FH) of premature coronary heart disease is unclear.

Methods and results

Multiethnic Study of Atherosclerosis enrolled 6814 adults without known atherosclerotic cardiovascular disease (ASCVD). Hard ASCVD events were ascertained over a median follow-up of 10.2 years. We estimated adjusted-hazard ratios for CAC and CIMT categories using Cox regression, both within and across FH status groups. Improvement in discrimination with CAC or CIMT added to variables from the ASCVD pooled cohort equation was also evaluated using receiver-operating characteristic curve and likelihood ratio analysis. Of 6125 individuals (62±10 years; 47% men) who reported information on FH, 1262 (21%) had an FH of premature coronary heart disease. Among these, 104 hard ASCVD events occurred. Crude incidence rates (per 1000 person-years) for hard ASCVD were 4.4 for CAC, 0 (n=574; 46% of the sample); 8.8 for CAC, 1 to 99 (n=368); 14.9 for CAC, 100 to 399 (n=178); and 20.8 for CAC, ≥400 (n=142). Relative to CAC=0, adjusted hard ASCVD hazard ratios for each CAC category among persons with an FH were 1.64 (95% confidence interval, 0.94-2.87), 2.45 (1.31-4.58), and 2.80 (1.44-5.43), respectively. However, there was no increased adjusted hazard for hard ASCVD in high versus low CIMT categories. In participants with an FH of premature coronary heart disease, CAC improved discrimination of hard ASCVD events (P<0.001). However, CIMT did not discriminate ASCVD (P=0.70).

Conclusions

Nearly half of individuals reporting FH have zero CAC and may receive less net benefit from aspirin or statin therapy. Among persons with an FH, CAC is a robust marker of absolute and relative risk of ASCVD, whereas CIMT is not.

Background and aims

Statins 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.

Methods

We 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.

Results

Participants (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.

Conclusion

CAC 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.

Arterial calcification reflects an atherosclerotic process associated with vascular stiffness. Whether baseline coronary artery calcium (CAC) and extra-coronary calcium (ECC), measured using noncontrast computed tomography imaging, are associated with incident hypertension is poorly understood. We studied participants from the Multi-Ethnic Study of Atherosclerosis without measured or self-reported hypertension at baseline. Incident hypertension was defined by blood pressure criteria (BP, ≥140/90 mmHg), BP medication use, or both, and was assessed at in-person visits. We analyzed incident hypertension using multivariable-adjusted discrete-time proportional hazards models. Net reclassification improvement (NRI) assessed whether CAC reclassified hypertension risk when added to the Framingham hypertension risk score. Among 3,304 subjects analyzed, mean age was 59 ± 10 years; 48% were male and 42% were white. There were 1,283 incident hypertension cases over a median (interquartile range) follow-up time of 10.6 (4.5, 11.5) years. Each 1-unit increase in ln(CAC+1) was independently associated with a 12% higher risk of hypertension (95% confidence interval [CI] 9% to 16%). Relative to CAC = 0, patients with CAC >400 had a hazard ratio for incident hypertension of 2.2 (95% CI 1.8 to 2.9). There was no interaction by age, gender, or baseline BP (p = 0.43, 0.19, 0.09, respectively). Continuous NRI analyses demonstrated that CAC can reclassify risk of incident hypertension; NRI = 0.19 (95% CI 0.10 to 0.26). Furthermore, all measurements of ECC were significantly associated with incident hypertension, even after adjustment for CAC (hazard ratios ranging from 1.36 to 1.38). In conclusion, patients with CAC and ECC are at markedly higher risk of incident hypertension and may benefit from more intensified prevention efforts.

Background and aims

South Asian (SA) ethnicity is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). However, the implications of considering SA ethnicity as a "risk-enhancing factor" per recent American College of Cardiology/American Heart Association guidelines are not fully understood.

Methods

We used data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, a community-based cohort study of individuals of SA ancestry living in the US. The Pooled Cohort Equations were used to estimate 10-year ASCVD risk. Metabolic risk factors and coronary artery calcium (CAC) scores were assessed.

Results

Among 1114 MASALA participants included (median age 56 years, 48% women), 28% were already using a statin at baseline, 25% had prevalent diabetes, and 59% qualified for 10-year ASCVD risk assessment for statin allocation purposes. The prevalence of low, borderline, intermediate, and high estimated ASCVD risk was 65%, 11%, 20% and 5%, respectively. Among participants at intermediate risk, 30% had CAC = 0 and 37% had CAC>100, while among participants at borderline risk, 54% had CAC = 0 and 13% had CAC>100. Systematic consideration of intermediate and, particularly, of borderline risk individuals as statin candidates would enrich the statin-consideration group with CAC = 0 participants up to 35%. Prediabetes and abdominal obesity were highly prevalent across all estimated risk strata, including among those with CAC = 0.

Conclusions

Our findings suggest that systematic consideration of borderline risk SAs as statin candidates might result in considerable overtreatment, and further risk assessment with CAC may help better personalize statin allocation in these individuals. Early, aggressive lifestyle interventions aimed at reducing the risk of incident diabetes should be strongly recommended in US SAs, particularly among those considered candidates for statin therapy for primary prevention. Longitudinal studies are needed to confirm the favorable prognosis of CAC = 0 in SAs.