PARTIAL ADHERENCE TO ANTIHYPERTENSIVE THERAPY FAILS TO ACHIEVE FULL CARDIOVASCULAR BENEFITS IN RATS WITH MALIGNANT HYPERTENSION.

Abstract

Purpose Hypertension is a major risk factor underlying cardiovascular morbidity and mortality. Adequate antihypertensive therapy prevents adverse cardiovascular events in hypertensive patients, but many patients do not adhere strictly to therapy and, in that way, may still be exposed to increased risk of unknown magnitude. Thus, we evaluated in quantitative terms cardiovascular risk inherent in partial therapy adherence experimentally in spontaneously hypertensive rats (SHRs). Methods Adult SHRs were given l-NAME to exacerbate hypertension and were divided into four groups: (1) controls, not given antihypertensive medication; (2) SHRs treated with candesartan (10 mg/kg/d) (perfect adherers); (3) SHRs given candesartan three times a week (intermittent adherers); and (4) SHRs given candesartan only during the last 6 days of a 3-week course of the experiment (visit-related adherers). A group of age- and sex-matched SHRs not given l-NAME was used for comparison. At the end, indices of systemic hemodynamics, blood flows and vascular resistances to target organs of hypertension (kidneys, brain, and heart), and indices of left ventricular function were determined. Results Treatment with l-NAME aggravated hypertension, adversely affected target organ blood flows and resistances, and grossly impaired heart function. Regular therapy with candesartan completely prevented all adverse cardiovascular effects of l-NAME. In partial adherers, arterial pressure decreased achieving control values (mean arterial pressure was 174 ± 3, 199 ± 7,* 170 ± 5, 182 ± 4, and 179 ± 5 mm Hg in rats given no L-NAME, SHRs given l-NAME only, and perfect, intermittent, and visit-related adherers, respectively). However, target organ hemodynamics and heart function showed only slight improvements, if any (thus, coronary flow reserve was 3.8 ± 0.3, 0.3 ± 0.4,* 3.9 ± 0.6, 2.1 ± 0.4,* and 1.1 ± 0.4* mL/min/g, whereas dP/dTmax, an index of systolic function, was 10,062 ± 309, 5,267 ± 476,* 9,721 ± 378, 8,673 ± 356,* and 6,234 ± 476* mmHg/s in rats given no l-NAME, SHRs given l-NAME only, and perfect, intermittent, and visit-related adherers, respectively) (*p Conclusions The results demonstrate that partial adherence to therapy may reduce arterial pressure but may not prevent target organ damage. Translated to humans, partial adherence to therapy with a subsequent decrease in arterial pressure may give a false sense of cardiovascular benefit.