Three decades of secondary prevention in ASCVD: temporal trends in risk factors and recurrent cardiovascular events

Abstract

Patients with established atherosclerotic cardiovascular disease (ASCVD) are at high risk of recurrent events. Over recent decades, guidelines have intensified secondary prevention strategies targeting risk factors, including low-density lipoprotein-cholesterol (LDL-c), systolic blood pressure (SBP), smoking cessation, adiposity, antithrombotic therapy, and emerging targets such as C-reactive protein (CRP). Evaluating long-term trends in risk factor control and clinical outcomes is essential to assess progress in secondary prevention and to identify persistent treatment gaps. To evaluate the change in cardiovascular (CV) risk factor levels and the risk of recurrent events in patients with established ASCVD. We included 10,175 ASCVD patients enrolled in the prospective UCC-SMART cohort (1996–2024) with coronary artery disease (CAD), cerebrovascular disease (CeVD), and peripheral arterial disease (PAD) including abdominal aortic aneurysm (AAA). Trends in CV risk factors (LDL-c, SBP, BMI, smoking, antithrombotic therapy, and CRP) were analyzed using linear or logistic regression, adjusted for age, sex, neighbourhood socioeconomic status (SES), and ASCVD location. Linear spline terms were applied for BMI and antithrombotic therapy, with knot placement based on the lowest AIC. To determine changes in recurrent events (myocardial infarction, stroke, CV death) over time, inclusion time was split into successive seven-year inclusion periods. Cox proportional hazards models were used to assess the risk of recurrent events across inclusion periods, adjusted for age, sex, SES, and ASCVD location. 3,721 recurrent events occurred during 100,252 person-years of follow-up. Apart from BMI, all risk factors consistently improved over time (Figure 1). Adjusted analyses showed declines per 5 years in LDL-c (-0.27 mmol/L, 95% CI -0.28 to -0.26), SBP (-2.7 mmHg, 95% CI -2.9 to -2.4), CRP (-17.5%, 95% CI -18.7 to -16.2), and smoking prevalence (-3.1%, 95% CI -3.6 to -2.6). BMI increased until 2004 (+0.7 kg/m², 95% CI 0.4 to 0.9) and then stabilized (0.0, 95% CI −0.1 to 0.1). Antithrombotic therapy increased until 2010 (+5.7%, 95% CI 4.8 to 6.5) and then plateaued (+0.5%, 95% CI −0.3 to 1.2). HRs for recurrent events declined progressively across inclusion periods for all ASCVD locations (Figure 2). This association remained substantial after adjustment for modifiable risk factor levels, with HRs decreasing across successive inclusion periods from 0.75 (95% CI 0.65 to 0.86) to 0.51 (0.40 to 0.64), indicating that improvements extended beyond measured changes in traditional risk factors. Over nearly three decades, patients with established ASCVD at different vascular locations achieved meaningful improvements in risk factor control and reductions in recurrent events. These findings reflect major advances in secondary prevention while highlighting persistent opportunities for further risk reduction.