Preindex Social Context and Cardiovascular Events Across Blood Pressure, LDL Cholesterol, and A1c Cohorts.

Abstract

Background: Cardiovascular prevention is organized around target metrics. Blood pressure, LDL cholesterol, and A1c define treatment targets, quality metrics, and, implicitly, who is considered safe. Yet a value below a cutoff is a correlative measurement, not an outcome. We tested whether social context recorded before the measurement separated subsequent cardiovascular events among people whose numbers already met the cutoff.

Methods: In this retrospective cohort study, we analyzed All of Us participants without recorded cardiovascular disease and with low comorbidity in three separately indexed cohorts: systolic blood pressure (SBP), LDL cholesterol, and A1c. A preindex score combined household income, education, food security, physical activity, and ZIP-linked deprivation, standardized against a fixed pooled reference of 325,652 eligible people. Cox models adjusted for the measured biomarker value, its square, a score-by-biomarker term, medication exposure, and clinical covariates. The outcome was first myocardial infarction, ischemic stroke, or heart failure. A sensitivity analysis indexed participants at the first measurement after the score became computable and counted only events recorded in inpatient or emergency settings.

Results: The SBP, LDL, and A1c cohorts included 19,525, 16,578, and 18,539 participants with 144, 129, and 191 events. Each one-SD more favorable score was associated with lower hazard: HR 0.611 (95% CI 0.498-0.749), 0.631 (0.512-0.778), and 0.544 (0.457-0.648), respectively. Below each study cutoff (SBP <140 mmHg, LDL <100 mg/dL, A1c <8%), less favorable context had event rates of 3.39 versus 1.68, 7.16 versus 2.05, and 8.67 versus 2.34 per 1,000 person-years. In a one-year analysis restricted to 2019-2023 index dates, the corresponding adjusted HRs were 0.530, 0.336, and 0.365. In the sensitivity cohorts (54,338, 41,451, and 33,607 participants; 493, 288, and 316 events), HRs were 0.732 (0.657-0.815), 0.660 (0.573-0.761), and 0.631 (0.552-0.722).

Conclusions: A biomarker below the study cutoff did not identify a uniform, low-risk population. Social context recorded before the measurement separated cardiovascular events after adjustment for the measured value and clinical factors. Risk assessment that stops at the number misses this variation.