Risk-Treatment Discordance and Fatal Cardiovascular Disease: A Nationwide Analysis Using PREVENT Thresholds

The 2026 multisociety dyslipidemia guideline adopted the PREVENT-ASCVD equations as the primary tool for identifying adults eligible for primary-prevention lipid-lowering therapy (LLT). The population-level treatment gap under this updated framework, and its relationship to fatal cardiovascular disease (CVD), have not been quantified.

Among 39,277 U.S. adults aged 30-79 years, 1,606 cardiovascular deaths occurred during follow-up; 38.5% occurred among individuals without baseline diagnosed CVD. Per-person risk was substantially higher among individuals with established CVD than among those without baseline CVD. Among 22,505 participants without baseline CVD with calculable PREVENT-ASCVD risk, 23.6% met the intermediate-or-higher risk threshold (≥5%), of whom 67.1% were not receiving LLT. At the borderline-or-higher threshold (≥3%), 35.9% met criteria, of whom 71.2% were untreated. Although per-person risk was substantially higher among individuals with established CVD (11.54 vs 0.97 per 1,000 person-years; P < 0.001), 38.5% (95% CI 35.2-41.8) of all cardiovascular deaths occurred in individuals without prior diagnosed CVD. Among individuals without baseline CVD, male sex, current smoking, and higher systolic blood pressure were independently associated with fatal CVD; diabetes was not independently associated after adjustment.

A majority of U.S. adults meeting contemporary PREVENT-ASCVD thresholds for LLT consideration are not receiving therapy, and a substantial share of fatal CVD occurs in this undertreated, primary-prevention population. Retrospective application of contemporary PREVENT thresholds suggests that substantial numbers of U.S. adults who subsequently experienced fatal cardiovascular disease would have met current treatment eligibility criteria yet were not receiving lipid-lowering therapy.