Statins and Blood Pressure Lowering: A Claim for Ad-Hoc Trials
To the Editor:
An interesting meta-analysis on the blood pressure–lowering effect of statins was recently been published in Hypertension.1 To obtain results of clinical significance, Strazzullo et al have performed a difficult and laborious review of randomized trials with rigid and very strict inclusion and exclusion criteria. Although there were limitations related to small sample size, inadequacy of previous study designs, heterogeneity of patients, therapies, duration of the trials, and statistical analyses, these limitations have been discussed by the authors. In addition, the most important beneficial vascular pleiotropic effects of statins have been considered and evidence that a clinically meaningful gain is achievable from their use has been provided.1
In agreement with the conclusions reached, we want to add some further possible limitations to the analysis that might be taken into account when planning future studies.
The trials considered in the metaanalysis included both overweight and obese patients/subjects. In addition, although the heterogeneity of dietary treatments has been carefully reviewed and exhaustively described, there was no possibility to investigate its role. However, no mention in the discussion has been provided with this regard.1 In some cases, diet-induced weight loss occurred, whereas in others no information on final body weight or BMI was available. Moreover, significant weight loss has been considered an important cause of blood pressure lowering (please see referenced trials included in the meta-analysis1).
If endothelial dysfunction represents an abnormality of hypercholesterolemic patients, obesity per se, in particular visceral adiposity, is independently associated with both2 and also with arterial hypertension.3 Moreover, progressive increase in body weight alters cholesterol metabolism through lowered absorption and increased synthesis.4 However, large doses of statin result in decreased synthesis and turnover and increased fractional and mass absorption of cholesterol.5 In addition, adherence to healthy dietary pattern is demonstrated to improve endothelial dyfunction,2,6 particularly when coupled to weight loss.6,7 Thus, diet and body weight might significantly contribute to overall improvement of endothelial function, blood pressure, and cholesterol metabolism. These considerations may also help to explain the lack of association between both baseline serum cholesterol and its reduction with the lowering of blood pressure observed by Strazzullo et al.1
In conclusion, the present metaanalysis highlights some potential beneficial effects achievable from drugs conceived for other purposes. This evidence should be considered, especially when cardiovascular disease prevention in at-risk patients frequently requires the contemporary treatment of several risk factors (eg, hypercholesterolemia, high blood pressure, diabetes). Finally, ad-hoc trials are clearly warranted.
Strazzullo P, Kerry SM, Barbato A, Versiero M, D’Elia L, Cappuccio FP. Do statins reduce blood pressure? a meta-analysis of randomized, controlled trials. Hypertension. 2007; 49: 792–798.
Perticone F, Ceravolo R, Candigliota M, Ventura G, Iacopino S, Sinopoli F, Mattioli PL. Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: protective effect of vitamin C. Diabetes. 2001; 50: 159–165.
Rahmouni K, Correia ML, Haynes WG, Mark AL. Obesity-associated hypertension: new insights into mechanisms. Hypertension. 2005; 45: 9–14.
Ziccardi P, Nappo F, Giugliano G, Esposito K, Marfella R, Cioffi M, D’Andrea F, Molinari AM, Giugliano D. Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation. 2002; 105: 804–809.