Combination therapy in hypertension: From effect on arterial stiffness and central haemodynamics to cardiovascular benefits

•Aortic stiffness and central haemodynamics are important biomarkers for risk prediction.•Antihypertensive treatment may mediate its benefits through improvement in such biomarkers.•ACE inhibitors reduce mortality in hypertension, whereas ARBs do not exhibit such a benefit.•ACE inhibitors and CCBs reduce CAD risk and stroke independently of blood pressure respectively.•Combining an ACE inhibitor with a CCB acts synergistically both at clinical and vascular level.

Measures of arterial aging have the potential to improve risk prediction beyond traditional risk scores. Such biomarkers that fulfil most, or some of the strict criteria of a surrogate end-point are aortic stiffness (IIa level of recommendation in European Guidelines and Position Papers) and central haemodynamics (IIb level of recommendation). Early intervention towards improving aortic elastic properties acquires particular importance since evidence suggests that arterial stiffening may occur before the onset of hypertension. Part of the beneficial effects of antihypertensive treatment in risk reduction may be mediated through improvement in aortic stiffness and central haemodynamics. However, not all antihypertensive drugs affect aortic stiffness and central haemodynamics in a similar way. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) have beneficial effects on such parameters. Meta-analytical approaches have shown that ACE inhibitors reduce mortality in hypertension, whereas ARBs do not exhibit such a benefit. Furthermore, ACE inhibitors have been shown to reduce the risk of coronary artery disease, and CCBs to reduce the risk of stroke independently of blood pressure reduction. Combining an ACE inhibitor with a CCB has the potential to reduce cardiovascular risk (synergy at the clinical level) by reducing aortic stiffness and improving central haemodynamics (synergy at the vascular level).