Prevention of congestive heart failure in high risk patients.

Congestive heart failure, in particular with preserved left ventricular ejection fraction, is increasing in incidence. Hypertensive disease is also increasing, and data suggest that this is a major contributor to the increasing incidence of congestive heart failure. In addition, there are data suggesting that patients with hypertension not only have a high prevalence of impaired left ventricular diastolic function, but in particular when left ventricular hypertrophy is present also have a high prevalence of impaired left ventricular myocardial function that in turn can lead to congestive heart failure. Furthermore, there are also data suggesting even more complex relationships between left ventricular systolic and diastolic function and that these conditions are in fact inter-related. We and others have shown that blood pressure reduction does in fact improve measures of left ventricular diastolic and systolic function. Furthermore, it has also been shown that improvement of the electrocardiographic strain pattern during antihypertensive treatment does reduce the risk of new-onset heart failure. It seems logical that if reduction in blood pressure can improve myocardial load by improving left ventricular systolic and diastolic function, this in turn would be associated with a reduced risk of subsequent heart failure. However, the data from the Blood Pressure Lowering Treatment Trialists’ Collaboration did not show any clear association between blood pressure reduction and reduced risk of congestive heart failure. Another question is whether the same pharmacological treatment used in congestive heart failure with depressed left ventricular ejection fraction is useful for the prevention of heart failure in patients with preserved left ventricular ejection fraction. The study of Verdecchia et al. is an interesting meta-analysis evaluating all relevant antihypertensive trials with the goal of estimating how much blood pressure reduction per se reduces risk of subsequent congestive heart failure. The analysis shows that greater blood pressure reduction leads to more prevention of congestive heart failure. For every 5 mmHg reduction in systolic blood pressure, the risk of congestive heart failure decreased by 24%. Furthermore, at any given level of blood pressure reduction, blockade of the renin–angiotensin system was superior to calcium channel blockade for prevention of congestive heart failure that is over and above the blood pressure reduction achieved. Furthermore, treatment with angiotensin-converting enzyme inhibitors (ACEIs) reduced the risk of congestive heart failure by 21% compared with placebo, while calcium channel blockers had no effect, but did on the other hand not increase the risk of congestive heart failure. ACEIs did not reduce the risk of congestive heart failure compared with b-blocker/diuretic combination therapy, while calcium channel blocker therapy was associated with an 18% increased risk of congestive heart failure compared with b-blocker/diuretic combination therapy. One major concern of the meta-analysis as a modus to derive additional information is that the input equals the output, and the information derived can be flawed by one large study with poor design overweighing smaller studies with proper design. This meta-analysis actually includes data from the large ALLHAT study; a study flawed by the inclusion of blacks with poor blood pressure response to treatment with renin–angiotensin-inhibiting therapy. It is reassuring that the authors have performed additional sensitivity analyses, estimating that ALLHAT did not exert significant influence on the overall estimates on the effect of ACEIs and angiotensin receptor blockers (ARBs) or calcium channel blockers vs. other active drugs. Another concern regards the assessments of congestive heart failure as an endpoint. The different studies are quite heterogeneous, with regard to independent adjudication, need for hospitalization, symptoms, echocardiography, X-ray, etc. Although all systematic reviews of current data on congestive heart failure share the same caveat, this introduces uncontrolled bias of a larger degree than when evaluating cardiovascular mortality,