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

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.

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.

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).

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.

Social, economic, and neighborhood conditions shape cardiovascular risk factors and predict cardiovascular events.Blood pressure, LDL cholesterol, and A1c targets anchor prevention and quality measurement, yet trials of treating to those targets show modest absolute reductions in hard outcomes.

After adjustment for the measured biomarker itself, each SD of more favorable preindex social context was associated with a 37% to 46% lower hazard of myocardial infarction, ischemic stroke, or heart failure across SBP, LDL cholesterol, and A1c cohorts. The association persisted, at 27% to 37%, in sensitivity cohorts 1.8 to 2.8 times larger.Below each biomarker cutoff, less favorable context carried 2- to nearly 4-fold higher observed event rates.A value below a study cutoff identifies a biomarker category; recorded social context identifies variation in subsequent events within that category.