Hypertension and coronary artery disease: Mechanistic insights and therapeutic challenges

The INTERHEART study recently documented that hypertension remains a major risk factor for myocardial infarction worldwide, in both sexes and at all ages [1]. Thus, there is a compelling need for better understanding the mechanisms linking hypertension to coronary artery disease, as well as for identifying factors influencing blood pressure control in hypertensive patients with ischaemic heart disease. The current issue of Blood Pressure includes two original papers, which deal with these issues.

Previous studies have shown that increased pulse pressure appears to be the most powerful factor identifying hypertensive patients at greatest risk for a subsequent myocardial infarction [2], [3]. Aortic stiffness is an independent predictor of primary coronary events in patients with essential hypertension [4]. Arterial stiffening assessed by measurement of pulse wave velocity is a strong independent predictor of cardiovascular morbidity and mortality [5–7]. The relationship between arterial stiffening and premature coronary artery disease is particularly striking in younger subjects (up to 60 years of age) [8].

In the current issue of Blood Pressure, Guray et al. [9] have shown an independent association between aortic pulsatility and presence of coronary artery disease in a cohort of female patients undergoing angiography. These findings are consistent with prior studies indicating that increased arterial stiffness might be associated with both coronary and carotid atherosclerosis [10], [11]. Factors underlying this association are not clear. Artery stiffness is an important determinant of heart rate control, transit of wave reflections and coronary perfusion [12]. Impairment of such mechanisms might contribute to initiation and/or progression of atherosclerosis. Furthermore, increased arterial stiffness may enhance left ventricular load and favour cardiac hypertrophy [5], further contributing to cardiac ischaemia, oxidative stress and plaque development. Other mechanisms might also be implicated. For example, activation of the sympathetic and renin–angiotensin systems have been linked to development of coronary atherosclerosis and to arterial stiffening. Finally, there is growing evidence that inflammation might not only contribute to atherosclerosis, but may also modulate arterial mechanical properties which promotes stiffening [13]. Taken together, these results indicate that impairment of large artery function (arteriosclerosis) and atherosclerosis often coexist and interact, share multiple pathophysiological mechanisms, and might jointly contribute to increased risk of cardiovascular disease.

Increased cardiovascular morbidity in treated hypertensives as compared with normotensives is largely due to remaining high systolic blood pressure levels in spite of treatment [14]. During therapy, progression of arterial stiffness is delayed only in patients with well‐controlled blood pressure [15]. Good blood pressure control is of particular importance in patients with coronary artery disease. Despite overwhelming evidence of benefit for intensive hypertension management, blood pressure is inadequately controlled in more than half of patients with coronary artery disease throughout Europe [16]. In this issue of Blood Pressure, Jankowski et al. [17] assessed factors influencing long‐term hypertension management in a cohort of more than 1000 patients with ischaemic heart disease. Their findings include, first, that older patients were less likely to achieve appropriate blood pressure control after discharge. Second, patients with unstable angina were more likely to remain without antihypertensive therapy than patients with myocardial infarction or those undergoing coronary artery bypass grafting. Third, a significant proportion of the patients with apparently normal blood pressure at discharge developed hypertension during the follow‐up. These findings might have important implications for understanding the challenges of hypertension management in secondary prevention. The authors attributed the unsatisfactory control of blood pressure in this high‐risk population to lack of patient education and under‐usage of combined therapy. Several other factors, including lack of lifestyle changes and psychosocial stress might also be implicated. Thus, while searching for new mechanisms linking hypertension to risk for coronary atherosclerosis, we should also focus on developing strategies for more effectively managing high blood pressure in those hypertensive patients in whom ischaemic heart disease is already established and symptomatic.