Association of hepatic steatosis with atherosclerotic cardiovascular events: A hospital-based case-control study from India.

Background: Hepatic steatosis, a recognised manifestation of systemic metabolic dysfunction, remains incompletely characterised in terms of its independent association with clinical atherosclerotic cardiovascular disease (ASCVD), particularly in South Asian populations where prior studies have relied on surrogate markers. Aim: To evaluate the association of objectively quantified hepatic steatosis with clinical ASCVD events in an Indian cohort. Design: Hospital-based, frequency-matched (age, sex, BMI) case-control study. Methods: 165 ASCVD cases and 165 controls were evaluated. Hepatic steatosis was quantified by vibration-controlled transient elastography (VCTE; FibroScan®) and examined for its independent association with ASCVD using multivariable logistic regression after adjustment for established cardiovascular risk factors. Dose-response relationships and phenotype-specific associations were additionally assessed. Results: Hepatic steatosis, modelled as a continuous CAP exposure, was independently associated with ASCVD (aOR 2.02 per 1-SD increase; 95% CI 1.48-2.75; p < 0.001), an association concentrated above an empirically-identified threshold of 260 dB/m (no association below this level, p = 0.73; strong association above it, p < 0.0001). Consistent with this, only severe steatosis (S3, ≥280 dB/m) was independently significant on categorical analysis (aOR 5.13; 95% CI 2.45-10.73; p < 0.001); mild and moderate grades were not. The association was predominantly driven by acute coronary syndrome; analyses for cerebrovascular accident and peripheral artery disease were limited by sample size. Unmatched cardiometabolic risk factors - diabetes, hypertension, smoking, and dyslipidaemia - behaved as expected, supporting model validity; age, sex, and BMI, the matched variables, showed the attenuated associations expected under frequency matching. Conclusion: VCTE-defined hepatic steatosis is independently associated with major ASCVD events in a severity-dependent manner in an Indian cohort. The observed association was primarily driven by ACS; CVA and PAD showed numerically elevated but non-significant associations and require validation in adequately powered cohorts. The association was concentrated at severe steatosis, consistent with a threshold rather than a linear dose-response effect. Given the cross-sectional design, temporal precedence between steatosis and ASCVD cannot be established. These findings suggest hepatic steatosis assessment may merit consideration within cardiovascular risk evaluation, particularly in high-risk South Asian populations, pending validation in prospective cohorts.