1. ○ South Asians (SAs) have high rates of CHD which are not entirely explained by traditional CVD risk factors. ○ The association of a family history of CHD (FH) with subclinical atherosclerosis as measured by CAC in SAs is unknown. ○ We sought to assess the association of FH with CAC in US SAs (MASALA) compared to four other ethnicities in the US (MESA). MASALA ○ Prospective cohort investigating the prevalence and outcomes associated with subclinical CVD in a community-based sample of 906 asymptomatic SA men & women aged 40-83 years, from San Francisco, CA & Chicago, IL. MESA ○ Prospective, population-based cohort investigating the characteristics of subclinical CVD & the risk factors that predict progression to clinically overt CVD in 6,814 asymptomatic men & women aged 45-84 from six US field centers. Study Population and Analysis ○ 802 MASALA & 6395 MESA participants were included. ○ FH was defined as 1 st relative who experienced a fatal or nonfatal MI or cardiac procedure (CABG, balloon angioplasty, & intracoronary stenting). ○ Multivariable regression models were used to assess the association of FH with CAC (>0, >100, and >400). ○ Multiplicative interaction testing was performed for race/ethnicity & FH (race/ethnicity*FH). ○ Likelihood ratio tests assessed the incremental predictive ability of FH to identify CAC (>0, >100, >400) when added to the 2013 ACC/AHA ASCVD risk estimate. o The absence of a significant association between FH and CAC in South Asians and Chinese Americans suggests possible ethnic differences in risk associated with FH, or possible misclassification of FH status in these two Asian subgroups. o Factors such as cohort age, educational achievement, coronary plaque morphology, and high rates of statin use in SAs with a positive FH may account for the lower prevalence of CAC compared to MESA. Table 2: The association between FH of CHD & CAC in each racial/ethnic group. o SAs were 4.5 years younger than others. o SAs had a high prevalence of diabetic & statin medication use. ○ The presence of FH was much lower in CAs (20%) compared to other ethnic groups. o FH is independently associated with CAC prevalence & burden in NHWs, AAs, & HPs. o FH is not significant associated with CAC prevalence in CAs & SAs. o FH was significantly associated with very high CAC (≥400) in SAs, but not in CAs. o FH added significantly (p 0 in NHWs, AAs, & LAs, and CAC>100 in NHWs & LAs. o In SAs, the addition of FH to the base model was not significant in predicting prevalent CAC>0 (p = 0.9) & CAC>100 (p = 0.3). Table 1: Baseline characteristics of family history positive individuals stratified racial/ethnic group. Figure 1: ROC Curve for CAC>0 vs. CAC=0. No difference in AUC with addition of FH to base model* (p = 0.9) Interaction testing by race/ethnicity in the association of FH-CAC>0 & FH-CAC>100 was not significant in unadjusted & adjusted models. * Variables from the 2013 PCE for ASCVD; AUC for base model = 0.835 (not shown). AUC=0.834 MESAMASALA p-value comparing FH+ groups Race/Ethnicity Non-Hispanic Whites African - Americans Hispanics Chinese Americans South Asians Total Population, N 2,4701,7821,405738802 Positive FH, N (%) 1,274 (52)747 (42)566 (40)147 (20)373 (47) - Age, years 63 (55-71)63 (54-69)62 (54-69)62 (53-70)56 (51-63) <0.001 Male* 562 (44)298 (40)253 (45)62 (42)183 (49) 0.056 Current Smoker* 150 (12)139 (19)84 (15)6(4)16 (4) <0.001 SBP mmHg* 125 (21)132 (21)128 (22)125 (22)127 (16) <0.001 Diabetes* 52 (4)78 (11)74 (13)13 (9)49 (13) <0.001 Fasting blood glucose mg/dl+ 88 (82-96)92 (84-103)93 (85-104)92 (86-100)97 (91-109) <0.001 Total Cholesterol mg/dl* 197 (36)191 (36)199 (38)193 (35)188 (38) <0.001 HDL Cholesterol mg/dL+ 50 (41-61)50 (41-60)46 (39-54)48 (40-57)48 (41-57) <0.001 Meds for DM* 65 (5)96 (13)87 (15)9 (6)75 (20) <0.001 Meds for HTN* 380 (30)395 (53)200 (35)43 (29)139 (37) <0.001 Lipid-Lowering Meds* 274 (22)142 (19)95 (17)30 (20)129 (35) <0.001 *mean (SD), + median (IQR). Abbreviations: FH – Family History of CHD, SBP – Systolic Blood Pressure, HDL – high density lipoprotein, DM – Diabetes Mellitus, HTN – Hypertension. MESAMASALA Race/EthnicityNHWsAAsHPsCAsSAs Unadjusted Regression Analysis, Odds ratio for the presence of calcification by race/ethnicity with a FH (95%CI) CAC>0 vs =0 1.6 (1.3 - 1.9)1.5 (1.2 - 1.8)1.7 (1.3 - 2.1)1.2 (0.9 - 1.8) 1.1 (0.9 - 1.5) CAC>100 vs ≤1001.6 (1.3 - 1.9) 1.5 (1.1 - 1.8)1.9 (1.5 - 2.5)1.1 (0.7 - 1.8) 1.2 (0.9 - 1.7) CAC>400 vs ≤4001.8 (1.4 - 2.3) 1.2 (0.9 - 1.8)2.2 (1.5 - 3.3)1.4 (0.7 - 2.7) 1.8 (1.1 - 3.1) Adjusted Regression Analysis, Odds ratio for the presence of calcification by race/ethnicity with a FH (95%CI) CAC>0 vs =01.7 (1.4 - 2.1) 1.6 (1.3 - 2.0)1.6 (1.2- 2.1)1.3 (0.9 - 2.0) 1.1 (0.7 - 1.5) CAC>100 vs ≤1001.8 (1.5 - 2.2) 1.5 (1.2 - 2.0)1.9 (1.4 - 2.6)1.3 (0.8 - 2.0) 1.3 (0.9 - 1.9) CAC>400 vs ≤4002.0 (1.6 - 2.7) 1.3 (0.9 - 1.9)2.2 (1.4 - 3.5)1.5 (0.7 - 3.2) 2.4 (1.3 - 4.3) * Adjusted for age, sex, smoking status, SBP, total cholesterol, HDL cholesterol, HTN medication use, and lipid-lowering medication.