Cardiometabolic risk factor burden and early cardiovascular disease onset among Asians: insights from the NIH All of Us cohort and Georgia OASIS

Moultrie, GA

INTRODUCTION: Cardiometabolic risk factors including diabetes, obesity, and smoking are major contributors to cardiovascular disease (CVD), yet the cumulative impact of multiple risk factors on age of onset across cardiovascular phenotypes remains incompletely defined. Cardiovascular risk patterns in Asian populations may differ from those in the general population, and the influence of cumulative cardiometabolic risk burden on early disease remains insufficiently characterized. Understanding how cardiometabolic risk burden influences early cardiovascular disease among Asians may help identify high-risk individuals and guide prevention strategies.

OBJECTIVES: To determine whether increasing cardiometabolic risk factor burden is associated with earlier cardiovascular disease onset among Asians and whether these patterns correspond to population-level cardiovascular morbidity and mortality.

METHODS: Clinical and demographic data were obtained from the NIH All of Us Research Program. Participants with documented diagnoses of coronary artery disease (CAD), hypertension (HTN), or stroke were identified through electronic health records. After applying inclusion criteria and removing duplicates, the final analytic cohort included 166,396 unique individuals, including 2,823 of Asian ancestry. Analyses were conducted in the overall cohort and Asian subgroup. Differences in age at diagnosis across phenotypes were evaluated using one-way ANOVA with Tukey post hoc comparisons, and associations with demographic or clinical variables were assessed using chi-square tests and logistic regression. Cardiometabolic risk factor burden was defined as the cumulative presence of obesity, diabetes, and smoking, and disease onset was evaluated using age thresholds of < 45, < 55, and < 65 years. Associations between increasing cardiometabolic risk factor burden and age thresholds were evaluated using trend analyses and logistic regression. Population-level emergency visits and cardiovascular mortality were examined using Georgia OASIS surveillance data and stratified by geography and age.

RESULTS: Age at diagnosis differed significantly across cardiovascular phenotypes (ANOVA F = 6866.64, p< 0.001). In the overall cohort, CAD was diagnosed 7.46 years later than hypertension and stroke 5.68 years later (both p< 0.001). Similar patterns were observed in the Asian subgroup, where CAD was diagnosed 7.28 years later than hypertension, and stroke 5.40 years later. In logistic regression comparing CAD with hypertension, diabetes increased CAD odds by 61%, male sex by 48%, and each additional year of age by 5%. Increasing cardiometabolic risk factor burden demonstrated a strong dose-response relationship with CAD prevalence; each additional risk factor increased odds of CAD before age 45 by 25%. Within the Asian subgroup, increasing risk factor burden was associated with earlier hypertension onset; each additional risk factor increasing odds of hypertension before age 45 by 13%. Population-level Georgia OASIS analyses demonstrated regional and age-stratified variation in cardiovascular emergency visits and mortality, with higher rates observed in rural districts and older populations.

CONCLUSION: Increasing cardiometabolic risk factor burden is strongly associated with earlier cardiovascular disease onset across multiple phenotypes. Among Asians, increasing risk factor burden is associated with earlier hypertension onset and similar age-of-onset patterns compared with the overall cohort. Population-level surveillance data demonstrate regional and age-related disparities in cardiovascular morbidity and mortality, highlighting the importance of early identification and aggressive management of cardiometabolic risk factors to reduce cardiovascular disease burden.