Large and Small Artery Cross-Talk and Recent Morbidity-Mortality Trials in Hypertension

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The results of recent large clinical trials in hypertension invite re-evaluation of the mechanisms of action of antihypertensive drugs on large and small arteries in the context of their effects on cardiovascular outcomes. By increasing our understanding of the relationship between large and small artery damage, target organ damage, and clinical end points, the trials provide us with new insights into the management of hypertension. This short review aims at analyzing the following: (1) whether β-blockers may exert deleterious effects on cardiovascular CV prevention through the reduction in heart rate (HR) or the lack of arterial remodeling; (2) whether long-term arterial remodeling can explain the “legacy” effect of multifactorial treatment in patients with hypertension and type 2 diabetes mellitus (T2D); and (3) to which level diastolic BP (DBP) can be safely lowered in elderly patients with isolated systolic hypertension (ISH). Because these issues have the concept of large/small artery cross-talk in common, we analyzed it first. The damaging effect of local pulse pressure (PP) has been well demonstrated on large arteries and, to a lesser extent, on small arteries. Elevated PP can stimulate hypertrophy, remodeling (increased media:lumen ratio), or rarefaction in the microcirculation, leading to increased resistance to mean flow. Recent studies showed a close relationship between microvascular damage in the heart, brain, retina, and kidney and either PP or arterial stiffness. Indeed, significant relationships have been demonstrated between brachial PP and glomerular filtration rate,1,2 microalbuminuria,2 or white matter lesions3; between arterial stiffness and glomerular filtration rate,4,5 urinary albumin,5 retinal arteriolar narrowing,6,7 white matter lesions,3 or cognitive function8; and between carotid stiffness and glomerular filtration rate.4,5 Although not all of these relationships are independent of confounding factors,3 there is a large amount of evidence for linking the pulsatility …