Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73,913 patients - Introduction

A Special Author Introduction
Journal of Hypertension
Official Journal of the European Society of Hypertension and the International Society of Hypertension

ISSN: 0263-6352 • Frequency: 12/year • Subscribe Now • Journal Website

By Gianpaolo Reboldi, Giorgio Gentile, Fabio Angeli, Giuseppe Ambrosio, Giuseppe Mancia and Paolo Verdecchia

Gianpaolo Reboldi, Giorgio Gentile, Fabio Angeli, Giuseppe Ambrosio, Giuseppe Mancia and Paolo VerdecchiaThe diabetes epidemic continues to grow, particularly in economically developing and newly industrialized countries. The projected number of diabetic patients worldwide will rise to 438 million in 2030. Concomitant hypertension is present in 40% or more of newly diagnosed type 2 diabetics, doubling total mortality and stroke risk, tripling the risk of coronary heart disease and significantly hastening the progression of diabetic nephropathy, retinopathy and neuropathy. In such patients, a difference of 5 mmHg in either systolic or diastolic blood pressure (BP) is associated with an increased risk of cardiovascular events or death by 20-30%.
Therefore, BP lowering is a major priority in preventing clinical events in patients with type 2 diabetes and hypertension. Although most guidelines suggest a systolic BP target lower than 130 mmHg, the recently published ACCORD BP trial showed no improvements in the composite primary outcome of non-fatal MI, stroke or CV death in the intensive BP-lowering arm (< 120 mmHg). The issue is further complicated by data from observational studies, including a post-hoc analysis from INVEST, suggesting that intensive BP lowering might cause an increased risk of cardiovascular events, the so-called J-curve. These data have led many organizations, including the European Society of Hypertension, to question the 130-mmHg target in diabetic patients.

We recently performed a meta-analysis of 31 intervention trials involving almost 74,000 patients, among which were five trials specifically targeted to tighter versus less tight BP control. Overall, we found that antihypertensive treatment reduced the risk of stroke by 9% (p=0.0059) and that of MI by 11% (p=0.0015). No clear differences between different drug classes were observed. Allocation to tighter versus less-tight BP control reduced the risk of stroke by 39% (relative risk 0.61; p<0.001) and showed a trend toward benefit for MI (RR 0.87; p=0.084). The findings apply to both systolic and diastolic BP, and the risk of stroke fell by 13% for each 5-mm-Hg systolic BP reduction and by 11.5% for each 2-mm-Hg diastolic BP drop. In contrast, the risk of MI did not show any significant association with the extent of BP reduction. In other words, a J-curve for coronary events was not observed and was effectively excluded down to a systolic BP level of 120 mmHg. The average BP levels across trials in the tightest control studies were 129/69 mmHg, which is at the border of what is currently recommended for diabetics.

Our results remove the potential concern for an increased risk of MI at low levels of achieved systolic BP (i.e 130 mmHg), which implies that these levels can be pursued in clinical practice. Intensive BP lowering is clearly appropriate for reducing the risk of stroke, which is a major debilitating event, in high-risk diabetics, does not increase the risk of coronary events, and indeed may produce coronary benefits.

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