Lanfranco D’Elia

Do statins reduce blood pressure?: a meta-analysis of randomized, controlled trials.

A meta-analysis was performed of the effect of 3hydroxy3methylglutaryl-coenzyme A reductase inhibitors (statins) on blood pressure in humans including the randomized, controlled trials of statin therapy (20 trials and 828 patients) in which concomitant antihypertensive treatment (if any) remained unchanged throughout the study. A total of 291 and 272 patients were given a statin or placebo, respectively, in parallel group trials, whereas 265 took part in crossover trials receiving a statin and placebo (or probucol, in 1 trial). Systolic blood pressure was significantly lower in patients on statin than in those on placebo or control hypolipidemic drug (mean difference: −1.9 mm Hg; 95% CI: −3.8 to −0.1). The effect was greater when the analysis was restricted to studies with a baseline systolic blood pressure >130 mm Hg (&Dgr; systolic blood pressure: −4.0; 95% CI: −5.8 to −2.2 mm Hg). There was a trend for lower diastolic blood pressure in patients receiving statin therapy compared with control: −0.9 mm Hg (95% CI: −2.0 to 0.2) overall and −1.2 mm Hg (95% CI: −2.6 to 0.1) in studies with a baseline diastolic blood pressure >80 mm Hg. In general, the higher the baseline blood pressure, the greater the effect of statins on blood pressure (P=0.066 for systolic blood pressure and P=0.023 for diastolic blood pressure). The blood pressure response to statins was unrelated to age, changes in serum cholesterol, or length of the trial. In conclusion, statin therapy has a relatively small but statistically significant and clinically meaningful effect on blood pressure.

Associations of selenium status with cardiometabolic risk factors: An 8-year follow-up analysis of the Olivetti Heart Study

OBJECTIVE High selenium status has been associated with adverse cardiometabolic outcomes in selenium-replete populations such as the US. In populations with lower selenium status such as in Italy, there is little epidemiological evidence about the association of selenium with cardiometabolic risk factors. We therefore examined cross-sectional and prospective relationships of serum selenium concentrations with cardiometabolic risk factors including blood pressure, diabetes and blood lipids in the Olivetti Heart Study. METHODS The study population consisted of 445 adult male individuals for whom baseline serum selenium measurement and cardiometabolic risk factors at baseline (1994-1995) and follow-up examination (2002-2004: average follow-up=8 years) were available. Serum selenium was measured by atomic absorption spectrophotometry. RESULTS Average serum selenium concentration at baseline was 77.5 ± 18.4 μg/L. In cross-sectional analyses, serum selenium levels were positively associated with serum total cholesterol (p for trend <0.0001) and prevalent diabetes (p for trend <0.05). In prospective analysis, serum selenium at baseline was likewise a strong predictor of serum total cholesterol (p=0.002) and LDL-cholesterol (p=0.001) at follow-up, after adjustment for age, BMI, cigarette smoking, physical activity, and lipid-lowering medication. These associations, however, were no longer significant after additional adjustment for baseline blood lipids. Selenium at baseline did not predict changes in total cholesterol levels between the baseline and follow-up examinations [β-coefficient (± SE)= 0.09 ± 0.12 (p=0.46)]. CONCLUSION These findings corroborate previous cross-sectional associations of high selenium status with adverse blood lipid profile and diabetes. However, prospective analyses do not support the causality of these relations. Randomized and experimental evidence is necessary to clarify the mechanisms underlying the observed cross-sectional associations.

Dietary salt intake and risk of gastric cancer.

Humans began to use large amounts of salt for the main purpose of food preservation approximately 5,000 years ago and, although since then advanced technologies have been developed allowing drastic reduction in the use of salt for food storage, excess dietary salt intake remains very common. Gastric cancer is a common neoplasia, and dietary factors, including salt consumption, are considered relevant to its causation. A number of experimental studies supported the cocarcinogenic effect of salt through synergic action with Helicobacter pylori infection, in addition to some independent effects such as increase in the rate of cell proliferation and of endogenous mutations. Many epidemiological studies analyzed the relationship between excess salt intake and risk of gastric cancer. Both cross-sectional and prospective studies indicated a possibly dose-dependent positive association. In particular, a comprehensive meta-analysis of longitudinal studies detected a strong adverse effect of total salt intake and salt-rich foods on the risk of gastric cancer in the general population. Altogether, the epidemiological, clinical, and experimental evidence supports the possibility of a substantial reduction in the rates of gastric cancer through progressive reduction in population salt intake.

Meta-Analysis of the Effect of Dietary Sodium Restriction with or without Concomitant Renin-Angiotensin-Aldosterone System–Inhibiting Treatment on Albuminuria

BACKGROUND AND OBJECTIVES Urinary albumin excretion and/or albumin to creatinine ratio are associated with CKD and higher risk of cardiovascular events. Several studies investigated the effect of reduced dietary sodium intake on urinary albumin excretion and/or albumin to creatinine ratio in adult patient populations, but the majority was inconclusive because of insufficient statistical power. A meta-analysis of the randomized, controlled trials available could overcome this problem and lead to more definitive conclusions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A systematic search of the online databases available (from 1996 to October of 2014) was conducted of randomized, controlled trials that expressed urinary albumin excretion or albumin to creatinine ratio as the difference between the effects of two different sodium intake regimens. For each study, the mean difference and 95% confidence intervals were pooled using a random effect model. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. RESULTS Eleven studies met the predefined inclusion criteria and provided 23 cohorts with 516 participants and 1-6 weeks of follow-up time. In the pooled analysis, an average reduction in sodium intake of 92 mmol/d was associated with a 32.1% (95% confidence interval, -44.3 to -18.8) reduction in urinary albumin excretion. The effect of sodium restriction was higher in the cohorts including patients on concomitant renin-angiotensin-aldosterone system-blocking therapy, in the studies with intervention lasting at least 2 weeks, and among participants with evidence of kidney damage. A greater reduction of urinary albumin excretion was associated with a higher decrease in BP during the intervention. The analysis of changes in albumin to creatinine ratio provided similar results. CONCLUSIONS This meta-analysis indicates that sodium intake reduction markedly reduces albumin excretion, more so during concomitant renin-angiotensin-aldosterone system-blocking therapy and among patients with kidney damage.

Not smoking is associated with lower risk of hypertension: results of the Olivetti Heart Study

BACKGROUND Few epidemiological investigations evaluated the role of smoking cessation on blood pressure (BP), and the results are not univocal. Therefore, the aim of this study was to assess the effect of smoking cessation on the risk to develop hypertension (HPT) and on BP values. METHODS This longitudinal study, with a follow-up period of 8 years, included the participants of the Olivetti Heart Study. Participants were 430 untreated normotensive non-diabetic men with normal renal function, examined twice in 1994-95 and in 2002-04. The sample included current smokers (S, n = 212), former smokers (ES, n = 145) and never smokers (NS, n = 73) at baseline. RESULTS Basal body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher in ES than in S (ES vs. S; BMI: 27.0 ± 2.5 vs. 26.1 ± 2.9 kg/m2; P < 0.01; SBP/DBP: 121.2 ± 9.3/80.0 ± 5.8 vs. 19.1 ± 9.9/77.4 ± 6.7 mm Hg; P < 0.05; M ± SD). After 8 years of follow-up, BP changes (Δ) were significantly lower in ES than in S (ΔSBP/DBP: 12.6 ± 13.4/7.9 ± 8.1 vs. 16.0 ± 14.9/10.3 ± 10.1 mm Hg; P < 0.05; M ± SD), also after adjustment for potential confounders. Moreover, at the last examination, the overall HPT prevalence was 33%, with lower values in ES than in S (25 vs. 38%, P = 0.01). After accounting for age, BP and BMI at baseline, and changes in smoking habit over the 8-year period, ES still had significant lower risk of HPT than S (odds ratio 0.30, 95% confidence interval 0.15-0.58; P < 0.01). CONCLUSIONS In this sample of healthy men, smoking cessation was associated with lower BP increment and minor HPT risk, independently of potential confounders.

Recommending Salt Intake Reduction to the Hypertensive Patient

The average individual dietary salt intake largely exceeds the physiological needs almost worldwide. A direct causal association between salt intake and blood pressure levels has been clearly established. Furthermore, there is increasing evidence for additional blood pressure-independent pathways linking excess salt intake to the process of atherosclerosis. Recent meta-analyses of randomized controlled trials showed that moderate reduction of salt intake is associated with reduction of blood pressure and, in perspective, with reduction of cardiovascular and cerebrovascular events in hypertensive individuals. According to the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines for the management of hypertension, instructions to reduce dietary salt intake to the level of 5 g/day based on the WHO recommendation should be provided to all patients, regardless of their requirement for drug treatment. Unfortunately, the patients’ response to this measure is heterogeneous, mainly due to variable compliance with the doctor’s prescription and to a lesser extent to different individual BP salt sensitivity.This article discusses the factors affecting the probability of a successful intervention focusing in particular on the doctor’s commitment to evaluate the patient’s dietary habits, to point out the main sources of salt in the patient’s diet, to provide the patient with adequate motivation and with proper instructions to implement gradual reduction of his/her salt intake, not disregarding the need for regular follow-up.

Response to Upregulation of Nitric Oxide, Inhibition of Oxidative Stress, and Antihypertensive Effects of Statins

We thank Zhou1 for his note on our meta-analysis of the effect of statin treatment on blood pressure. Zhou pointed out the potential impact of statin therapy on the imbalance between NO and reactive oxidative species production occurring in animal models of salt-sensitive hypertension.2 This ability of statins was indeed the basis for one of the explanations that we proposed for the relatively small but clinically meaningful antihypertensive effect of these drugs in humans.3 We share Zhou’s considerations and recollect the experimental evidence in support of the concept that genetic or acquired susceptibility to …

Coffee consumption and risk of hypertension: a dose–response meta-analysis of prospective studies

PurposeRecently, a large prospective study provided additional information concerning the debated possible association between habitual coffee consumption and risk of hypertension (HPT). Therefore, we updated the state of knowledge on this issue by carrying out a comprehensive new systematic review of the literature and a meta-analysis of the available relevant studies.MethodsWe performed a systematic search for prospective studies on general population, published without language restrictions (1966–August 2017). A random-effects dose–response meta-analysis was conducted to combine study specific relative risks (RRs) and 95% confidence intervals. Potential non-linear relation was investigated using restricted cubic splines.ResultsFour studies (196,256 participants, 41,184 diagnosis of HPT) met the inclusion criteria. Coffee intake was assessed by dietary questionnaire. Dose–response meta-analysis showed a non-linear relationship between coffee consumption and risk of HPT (p for non-linearity < 0.001). Whereas the habitual drinking of one or two cups of coffee per day, compared with non-drinking, was not associated with risk of HPT, a significantly protective effect of coffee consumption was found starting from the consumption of three cups of coffee per day (RR = 0.97, 95% CI = 0.94 to 0.99), and was confirmed for greater consumption.ConclusionsThe results of this analysis indicate that habitual moderate coffee intake is not associated with higher risk of HPT in the general population and that in fact a non-linear inverse dose–response relationship occurs between coffee consumption and risk of HPT.

Effect of statin therapy on pulse wave velocity: A meta-analysis of randomized controlled trials

ABSTRACT Background and Objective: Arterial stiffness (AS) is an independent cardiovascular risk factor. A number of studies have reported a beneficial role of statins on AS albeit with controversial results, in addition to their effects on lipid profile. Therefore, we carried out a meta-analysis of the available randomized controlled trials assessing the effects of statin therapy on AS, in the attempt to reach more definitive conclusions. Methods: A systematic search of the on-line databases available up to March 2017 was conducted, including intervention studies reporting AS expressed by carotid-femoral pulse wave velocity (PWV), as difference between the effects of treatment with or without statins. For each study, mean difference (MD) and 95% confidence intervals (CI) were pooled using a random effect model. Results: Eleven studies met the pre-defined inclusion criteria, for a total of 573 participants and 2–144 weeks’ intervention time. In the pooled analysis, statin therapy was associated with a −6.8% (95% C.I.: −11.7 to −1.8) reduction in PWV. There was significant heterogeneity among studies (I2 = 96%); none of the study characteristics seems to have influenced the effect of statin use on PWV. Conclusions: The results of this meta-analysis suggest that statin therapy reduces AS. This effect appears to be at least in part independent of the changes in blood pressure and lipid profile.

Excess Body Weight, Insulin Resistance and Isolated Systolic Hypertension: Potential Pathophysiological Links

Isolated systolic hypertension, the most common form of hypertension in the elderly, but also detectable among young and middle-aged subjects, is independently associated with higher risk of cardiovascular events and all-cause mortality. Among various pathophysiological changes associated with aging, excess body weight and insulin resistance may predispose to this type of hypertension. Overweight or frank obesity and their frequent companion insulin resistance could mediate the development of isolated systolic hypertension through increase in the renin–angiotensin–aldosterone system activity, in the sympathetic tone and in salt-sensitivity, all in turn leading to endothelial dysfunction, arterial stiffness and increase in blood pressure. This review will focus on this cluster of pathophysiological factors and on the mechanistic pathways whereby they may favor the development of isolated systolic hypertension.