Cardiovascular Outcomes in Middle-Aged Adults on Antihypertensive Medications and No Prior Cardiovascular Disease

Middle-aged adults with hypertension and no prior cardiovascular disease are commonly seen in clinical practice, yet limited research exists on optimal antihypertensive therapy for this group. This study evaluated whether cardiovascular outcomes vary by antihypertensive drug classes in this population.

Using the Korean National Health Insurance Service database, we analyzed individuals aged <60 years without cardiovascular disease who were prescribed antihypertensive drugs between 2013 and 2014. Patients on monotherapy were grouped by drug class; those on ≥2 drug classes or uncommon agents (eg, alpha-blockers, hydralazine, or mineralocorticoid receptor antagonists) were categorized as "Others." A subgroup analysis compared outcomes between different angiotensin receptor blockers (ARBs). The primary outcome was a composite of cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, and hospitalization for heart failure.

A total of 217,617 participants were included; ARBs were the most common monotherapy (n = 59,906, 27.5%). During follow-up, 3.3% (n = 7080) experienced the primary outcome. The highest incidence of the primary outcome, all-cause death, and cardiovascular death occurred in the diuretic group, and the lowest observed rates were in the ARB group (P < 0.001). In multivariable analysis, beta-blockers (hazard ratio [HR] = 1.81, 95% confidence interval [CI] = 1.48-2.22, P < 0.001) and diuretics (HR = 2.09, 95% CI = 1.70-2.57, P < 0.001) were associated with higher event rates compared with the angiotensin-converting enzyme inhibitor reference group. No statistically significant differences were detected among the individual ARBs evaluated.

Among middle-aged adults with hypertension and no prior cardiovascular disease, ARB users had the lowest observed cardiovascular event rates in this cohort. The higher event rates observed with beta-blockers and diuretics likely reflect confounding by indication. These hypothesis-generating findings require confirmation in prospective studies.