Cardiovascular risk in patients receiving antihypertensive drug treatment from the perspective of endothelial function

Blood-pressure-lowering therapy with antihypertensive drugs can reduce the risk of cardiovascular morbidity and mortality in patients with hypertension. However, patients treated with antihypertensive drugs generally have a worse prognosis than untreated individuals. Consistent with the results obtained from epidemiological studies, a clinical study showed that endothelial function was impaired more in treated patients with hypertension than in untreated individuals with the same blood pressure level, suggesting that blood-pressure-lowering therapy with currently available antihypertensive drugs cannot restore endothelial function to the level of that in untreated individuals. Several mechanisms of endothelial dysfunction in treated patients are postulated: irreversible damage to the endothelium caused by higher cumulative elevated blood pressure exposure over time; the persistence of the primary causes of hypertension even after the initiation of antihypertensive drug treatment, including an activated renin-angiotensin-aldosterone system, oxidative stress, and inflammation; and higher global cardiovascular risk related not only to conventional cardiovascular risk factors but also to undetectable nonconventional risk factors. Lifestyle modifications/nonpharmacological interventions should be strongly recommended for both untreated and treated individuals with hypertension. Lifestyle modifications/nonpharmacological interventions may directly correct the primary causes of hypertension, which can improve endothelial function and consequently reduce cardiovascular risk regardless of the use or nonuse of antihypertensive drugs.