Lionel H. Opie

Background— Hypertension in sub-Saharan Africa is a widespread problem of immense economic importance because of its high prevalence in urban areas, its frequent underdiagnosis, and the severity of its complications. Methods and Results— We searched PubMed and relevant journals for words in the title of this article. Among the major problems in making headway toward better detection and treatment are the limited resources of many African countries. Relatively recent environmental changes seem to be adverse. Mass migration from rural to periurban and urban areas probably accounts, at least in part, for the high incidence of hypertension in urban black Africans. In the remaining semirural areas, inroads in lifestyle changes associated with “civilization” may explain the apparently rising prevalence of hypertension. Overall, significant segments of the African population are still afflicted by severe poverty, famine, and civil strife, making the overall prevalence of hypertension difficult to determine. Black South Africans have a stroke rate twice as high as that of whites. Two lifestyle changes that are feasible and should help to stem the epidemic of hypertension in Africa are a decreased salt intake and decreased obesity, especially in women. Conclusions— Overall, differences from whites in etiology and therapeutic responses in sub-Saharan African populations are graded and overlapping rather than absolute. Further studies are needed on black Africans, who may (or may not) be genetically and environmentally different from black Americans and from each other in different parts of this vast continent.

# Direct comparative studies are needed {#article-title-2} Editor—The editorial by Verma and Strauss does not accord with the BMJ 's usual impartial evidence based approach.1 Evidence that angiotensin receptor blockers increase myocardial infarction is scant, and I remain puzzled about what exactly patients should be told—that the BMJ published an incorrect analysis? Regarding angiotensin receptor blockers and myocardial infarction in hypertension, the …

The negative results of glucose-insulin-potassium (GIK) in the very large CREATE-ECLA trial that studied 20 201 patients with ST-elevation acute myocardial infarction (AMI), are disappointing and warrant thorough evaluation. We attempt to put the new data into perspective and uncover the serious flaws in the trial design, otherwise the whole metabolic concept will be disparaged. The crucial issue, developed from basic science data, is that GIK should be initiated very early, before, or at the time of reperfusion. Another problem with CREATE-ECLA is that the mortality in Killip class 1 reperfused patients was 7.1%, much higher than that of a recent Dutch study in which mortality was only 1.2%. Nonetheless, there was a strong trend towards a lower mortality in the sub-groups that received the best reperfusion therapy in CREATE-ECLA, as well as in the first of two rather small Dutch GIK trials. In the future, the ideal protocol to test would be if GIK were given in the ambulance as the patient is being transported to a specialized centre of percutaneous coronary intervention (PCI), with the aim of expanding the time window between pain onset and actual PCI.

Diuretic antihypertensive therapy is recommended as first choice by many guidelines, often in combination with β-blockers. However, such recommendations are based on relatively short-term trials, whereas treatment for hypertension is often a lifetime process. A meta-analysis of seven studies in 58 010 individuals, showed that the ‘new’ therapies, namely angiotensin-converting enzyme (ACE) inhibitors, angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) provoke less new diabetes than the conventional ‘old’ therapies (diuretics and β-blockers). ACE inhibitors/ARBs decreased new diabetes by 20% ( P < 0.001), whereas CCBs decreased new diabetes by 16% ( P < 0.001). The number needed to treat for approximately 4 years by new rather than old conventional therapy to avoid one case of new diabetes is about 60–70. Other factors contributing to increased coronary risk are increased metabolic syndrome, blood lipid changes and hypokalaemia. It is not certain whether it is the new therapy that provides protection against new diabetes or the conventional therapy that precipitates new diabetes. However, when compared with placebo, ACE inhibition by ramipril or by the ARB, candesartan, both decrease the incidence of new diabetes, raising the hypothesis that these agents actually prevent the changes leading to insulin resistance, possibly by lessening the adverse effects of angiotensin II on the endothelium. Conversely, lipid abnormalities with conventional treatment could exert adverse effects on the endothelium. Therefore endothelial changes could help to explain the benefits of ‘modern’ treatment compared with the defects of conventional therapy.

Preconditioning a powerful protective mechanism, is the response to transient ischemia and reperfusion. However, the best way to achieve total protection is to avoid ischemia altogether. Therefore prevention of ischemia and protection by preconditioning are differently mediated so that anti-ischemic agents may not precondition, whereas paradoxically pro-ischemic agents may precondition. Metabolically active agents such as glucose-insulin-potassium, trimetazidine and ranolazine that protect from ischemia, increase glucose metabolism relative to that of fatty acids. By promoting glycolysis they tend to close the ATP-dependent potassium channels that help to mediate preconditioning. By lessening the oxygen-wasting effects of fatty acids, they are mitochondrial protective and oxygen-sparing. These qualities should help in the therapy of myocardial ischemia and also heart failure.