Stefano Bacchelli

Use of statins and blood pressure control in treated hypertensive patients with hypercholesterolemia

High serum cholesterol has been frequently reported in patients with arterial hypertension in whom it might influence the blood pressure control. The aim of this study was to compare the extent of blood pressure changes in 41 patients with hypertension and hypercholesterolemia, taking antihypertensive drugs and treated for 3 months with statins (HC-S; pravastatin or simvastatin) and compared with matched controls with high (HC-D; 44) or normal serum cholesterol (NC-D; 45) undergoing antihypertensive treatment combined with dietary treatment alone. After 3 months of follow-up, a greater reduction of systolic (SBP) and diastolic (DBP) blood pressure values was observed in HC-S patients (ASBP/DBP, -11.3 +/-3/-10.6 +/- 2%) when compared with both HC-D (deltaSBP/DBP, -6.6 +/- 2/-6.1 +/- 2%; p < 0.05) and NC-D (deltaSBP/DBP, -6.9 +/- 2/-6.8 +/- 1.5%; p < 0.05). In statin-treated patients, a slight linear relation has been found between the percentage changes in DBP and those in plasma total cholesterol (R = 0.37, p = 0.043), whereas no relation was found with SBP changes (R =0.11; p = 0.35). In conclusion, the results of this study demonstrate that the use of statins in combination with antihypertensive drugs can improve blood pressure control in patients with uncontrolled hypertension and high serum cholesterol levels. The additional blood pressure reduction observed in patients treated with statins is clinically relevant and only partially related to the lipid-lowering effect.

Effects of the administration of an angiotensin-converting enzyme inhibitor during the acute phase of Myocardial infarction in patients with arterial hypertension

A positive history of arterial hypertension (HBP) is present in as many as 30% of patients with acute myocardial infarction (AMI) and their clinical outcome could be greatly improved by drugs enhancing blood pressure control and preserving ventricular function. The aim of the present study was to evaluate the importance of a history of HBP on the clinical efficacy of early treatment with the angiotensin-converting enzyme (ACE) inhibitor zofenopril in patients with anterior AMI. We summarize the results of a post-hoc analysis of data from the Survival of Myocardial Infarction Long-term Evaluation (SMILE) study, which randomly evaluated the efficacy of zofenopril given within 24 h of symptom onset to patients with anterior AMI not undergoing thrombolysis. Of 1441 patients who entered the study, 565 (39.2%) had a history of HBP. The mean follow-up time was 12 months and the main outcome measures were 6-week combined occurrence of death and severe congestive heart failure (CHF) and 1-year mortality. After 6-week of treatment with zofenopril the relative risk of death or severe CHF was 0.60 (95% confidence interval [CI]: 0.45-0.81; 2P < .05) in the hypertensive group and 0.89 (0.74-1.08; 2P = .62) for normotensive patients, whereas the 1-year risk of death was 0.61 (95% CI: 0.23,0.89; 2P < .05) and 0.77 (95% CI: 0.52-1.17; 2P = .22), respectively. The 6-week prevalence of mild-to-moderate CHF was also significantly reduced by zofenopril in the hypertensive population (14.1% v 9.4%; 2P < .05). The present data suggest that treatment with zofenopril started within 24 h of the onset of anterior AMI could be highly beneficial in patients with a history of HBP.

Factors associated with the development of stable hypertension in young borderline hypertensives

Objectives To identify factors predisposing subjects to the development of stable hypertension and to estimate their relative importance in 70 young patients with borderline hypertension monitored for 10 years. Design Longitudinal evaluation of the incidence of stable hypertension [diastolic blood pressure (DBP) > 95 mmHg]. Methods Patients were examined at baseline by determination of resting blood pressure, intracellular sodium level and individual pressor response to mental arithmetic and to intravenous saline loading. They were re-examined after 10 years to assess the prevalence of established hypertension and the importance of some prognostic variables identified prospectively (age, sex, intracellular sodium level, baseline blood pressure, pressor response to stress and acute salt-sensitivity). Results The prevalence of sustained hypertension (DBP > 95 mmHg) was 35.8% after 10 years of follow-up study. Subjects developing hypertension were older (26.9±1.3 versus 21.0±1.8 years) and showed a higher percentage of family history of hypertension (92 versus 64%) and of acute salt-sensitivity (72 versus 53%). The pressor response to mental arithmetic was greater in patients who developed hypertension (systolic blood pressure 26.9±1 versus 22.7±0.9 mmHg, P=0.005 DBP = 16.6±0.8 versus 13.1±0.7 mmHg, P=0.005), who also showed higher levels of intracellular sodium (30.7±0.6 versus 27.3±0.5 mmol/kg, P=0.001). The same variables were found to be related to the development of hypertension in a multivariate analysis and the concomitant presence of 4–5 risk factors was associated with a reasonable predictive power for the identification of patients at high risk (sensitivity 72%, specificity 67%, predictive accuracy 76%). Conclusions The present study demonstrates that borderline hypertensives at high risk of stable hypertension can be identified by the concomitant evaluation of some clinical and cellular characteristics directly related to long-term development of high blood pressure.

Lactotripeptides effect on office and 24-h ambulatory blood pressure, blood pressure stress response, pulse wave velocity and cardiac output in patients with high-normal blood pressure or first-degree hypertension: a randomized double-blind clinical trial

Contrasting data partially support a certain antihypertensive efficacy of lactotripeptides (LTPs) derived from enzymatic treatment of casein hydrolysate. Our aim was to evaluate this effect on a large number of hemodynamic parameters. We conducted a prospective double-blind randomized clinical trial, which included 52 patients affected by high-normal blood pressure (BP) or first-degree hypertension. We investigated the effect of a 6-week treatment with the LTPs isoleucine–proline–proline and valine–proline–proline at 3 mg per day, assumed to be functional food, on office BP, 24-h ambulatory BP monitoring (ABPM) values, stress-induced BP increase and cardiac output-related parameters. In the LTP-treated subjects, we observed a significant reduction in office systolic BP (SBP; −5±8 mm Hg, P=0.013) and a significant improvement in pulse wave velocity (PWV; −0.66±0.81 m s−1, P=0.001; an instrumental biomarker of vascular rigidity). No effect on 24-h ABPM parameters and BP reaction to stress was observed from treatment with the combined LTPs. LTPs, but not placebo, were associated with a mild but significant change in the stroke volume (SV), SV index (markers of cardiac flow), the acceleration index (ACI) and velocity index (VI) (markers of cardiac contractility). No effect was observed on parameters related to fluid dynamics or vascular resistance. LTPs positively influenced the office SBP, PWV, SV, SV index, ACI and VI in patients with high-normal BP or first-degree hypertension.

Serum cholesterol levels, blood pressure response to stress and incidence of stable hypertension in young subjects with high normal blood pressure

Rationale Elevated serum cholesterol levels are common in patients with high blood pressure (BP) and could contribute to the progression of the hypertensive disease. Objective To determine whether serum cholesterol levels affect the BP response to mental stress (MA) and the development of stable hypertension in young subjects with high normal BP. Methods Seventy young (age < 45 years) high normal BP subjects with elevated (> 200 mg/dl, n = 49; HC) or normal (⩽ 199 mg/dl, n = 21; NC) serum cholesterol levels, and 20 normotensive normocholesterolaemic (serum cholesterol < 199 mg/dl; C) subjects undergoing standardized mental challenge (mental arithmetic) were followed up for 15 years according to a prospective, longitudinal, cohort study design conducted in an ambulatory setting. The main outcome measure was the evaluation of the 15-year incidence of stable hypertension (diastolic BP > 95 mmHg). Results After adjustment for age, resting BP, family history of high BP and body mass index at the study entry, high normal BP subjects with HC showed an enhanced BP reactivity to stress and a higher 15-year incidence of stable hypertension compared to high normal BP and NC subjects [relative risk (RR) = 2.1; 95% confidence interval (CI) = 1.7–5.5, P < 0.001] and controls (RR = 3.1; 95% CI = 1.4–5.3, P < 0.001). In a multivariate analysis of data the presence of high cholesterol levels was an independent predictor for the development of hypertension. Conclusion These data suggest that subjects with high normal BP and elevated serum cholesterol might have an exaggerated cardiovascular response to stress and have an increased risk for stable hypertension that can be detected at young age.

A review of the angiotensin-converting enzyme inhibitor, zofenopril, in the treatment of cardiovascular diseases

Based on preclinical and clinical findings, zofenopril appears to be an angiotensin-converting enzyme (ACE) inhibitor with high potency, significant tissue selectivity and a long duration of action. Its ancillary properties, such as antioxidant activity and cardiovascular (CV) protection, make this drug potentially suitable for the treatment, and possibly prevention, of several CV diseases. There is a large body of evidence that support a complex interaction between ACE inhibitors and CV disease. A review of the preclinical profile of zofenopril clearly suggest that such interaction can be even more complex and could involve some drug-specific properties directly involved in the definition of the overall clinical profile of zofenopril as emerged from randomised clinical trials. In particular, zofenopril combines the feature of an effective ACE inhibitor, with plasma and tissue activity, along with that of an antioxidant compound, and both these characteristics can contribute to its capacity of controlling hypertension and improving the prognosis of patients with coronary artery disease. The results of The Survival of Myocardial Infarction Long term Evaluation (SMILE) trials have demonstrated that the early administration of zofenopril to patients with acute myocardial infarction is associated with a significant reduction in the 6-week occurrence of major CV events (death and congestive heart failure) in high-risk patients with anterior non-thrombolysed myocardial infarction, and this effect is enhanced in some higher-risk subgroups of patients, such as those with a history of diabetes or arterial hypertension.

ACE-inhibitors and atherosclerosis

The involvement of the circulating and local renin-angiotensin system in atherosclerotic process has been hypothesized on the basis of experimental data showing presence and specific actions of the components of this system in the vascular wall. In particular, angiotensin II may participate in well known events in atherogenesis as the control of smooth muscle cell growth and proliferation.Recent studies have shown an effect of angiotensin converting enzyme (ACE) inhibition on the development of atherosclerosis in animal models. Captopril and cilazapril prevent myointimal proliferation after vascular injury in rat. Captopril reduces aortic cholesterol content and percentage intmal aortic surface covered by lesions in Watanabe heritable hyperlipidemic rabbits. Captopril also significantly reduces the progression of carotid and coronary lesions in monkeys fed a high cholesterol diet. In addition, a role for converting enzyme inhibitors in reducing aortic and microvascular growth either in hypertensive or normotensive rats has been demonstrated. It is possible that ACE-inhibitors prevent angiotensin II-induced vascular proliferation and thereby suppress the development of atherosclerosis in animals. It is also conceivable that the blood pressure effects of ACE-inhibitors could play a role in the antiatherosclerotic effect shown by these drugs, even though this explanation cannot be addressed by studies dealing with normotensive animals. Then, other mechanisms could be involved, including hypothesized effects of blockade of the renin-angiotensin system on sympathetic nervous system activity, regulation of vascular growth factors and insulin sensivity.The clinical significance of these experimental findings is unknown. Molecular mechanisms by which the renin-angiotensin system can act on atherosclerosis pathogenesis and the influence of ACE-inhibitors on the course of arterial diseases in humans ought to be important subjects of future investigations.

Hemodynamic and neurohumoral profile in patients with different types of hypertension in pregnancy

Hypertension in pregnancy is a frequent disorder that includes a spectrum of conditions. We aimed at comparatively evaluating the hemodynamic, echocardiographic and biohumoral profile of a sample of pregnant Caucasian women with different form of pregnancy-related hypertension. We enrolled 39 non-hypertensive pregnant women (NP), 26 with Chronic HBP in pregnancy (CH), 24 with gestational hypertension (G-PIH), and 33 with pre-eclampsia. We recorded and compared blood pressure (BP), echocardiographic parameters, resting plasma renin activity (PRA) and plasma aldosterone (PA), Plasma levels of atrial (ANP) and brain natriuretic peptide (BNP). PE patients had a significantly higher BP than either G-PIH or NP patients. PE patients had also significantly lower cardiac output than NP, G-PIH and CH. In comparison to NP patients, the total peripheral vascular resistance was 61% higher in PE women and 38% higher in CH patients. All echographic parameters were significantly more altered in PE patients when compared with NP, in respect to any other form of hypertension. Either ANP (+35%) and BNP (+40%) were significantly higher in PE patients than in controls. The PRA was reduced in PE and CH patients when compared either with NP (−38 and −35%, respectively) or G-PIH (−47 and −43%, respectively). On the basis of our data, we can conclude that PE is the gestation associated hypertension with the largest anatomical, functional and biohumoral involvement, and so it has to be involved in a more intensive monitoring and evaluation.

Hemodynamic Effects of Lactotripeptides from Casein Hydrolysate in Mediterranean Normotensive Subjects and Patients with High-Normal Blood Pressure: A Randomized, Double-Blind, Crossover Clinical Trial

Contrasting data partially support a certain antihypertensive efficacy of lactotripeptides derived from enzymatic treatment of casein hydrolysate. We carried out a randomized, double-blind, crossover clinical study to investigate the antihypertensive efficacy of a short-term treatment with lactotripeptides in Mediterranean subjects with normal or high-normal blood pressure (BP). We consecutively enrolled 55 untreated subjects (men:women = 30:25), 40.3 ± 9.8 years old, with normal or high-normal BP. After 4 weeks of dietary standardization, they were allocated to treatment with a fruit juice containing 3 mg of added Ile-Pro-Pro/Val-Pro-Pro lactotripeptides or with placebo for 4 weeks. After a 4-week washout period, they were then assigned to the alternative treatment for a further period of 4 weeks. Overall, no significant difference has been observed in office BP comparing baseline data with those posttreatment. Repeating the analysis by basal BP level, a mild but significant reduction in systolic BP (-1.7 ± 2.3 mm Hg; t = 3.5, P = .002) has been observed only in subjects with high-normal BP after treatment with lactotripeptides. With regard to 24-hour BP measurement, after lactotripeptide treatment only, the subjects experienced a significant reduction in diurnal diastolic BP (-1.6 ± 5.4 mm Hg; P = .042), diurnal mean BP (-2.1 ± 5.9 mm Hg; P = .19), and 24-hour (-5.4 ± 14.2 mm Hg; P = .011) and diurnal (-7.1 ± 19.2%; P = .014) diastolic BP value measurements relative to normal values. No modification has been observed in relation to plasma renin activity and aldosteronemia. In conclusion, diurnal diastolic BP is significantly reduced by lactrotripeptide supplementation in untreated Mediterranean subjects with normal or high-normal BP. Office systolic BP is reduced only in subjects with high-normal BP.

Serum uric acid and other short-term predictors of electrocardiographic alterations in the Brisighella Heart Study cohort

INTRODUCTION Recent studies show that serum uric acid (SUA) is a predictor of atrial fibrillation, while its association with other kinds of arrhythmias is not yet established. We aimed to evaluate the incidence of the most common electrocardiographic alterations in a relatively large sample of general population and their association with SUA. MATERIALS AND METHODS We selected a Brisighella Heart Study cohort sample of 1557 subjects, consecutively visited in the 2004 and 2008 surveys, in a setting of primary prevention for cardiovascular disease and without a known diagnosis of arrhythmia or left ventricular hypertrophy, excluding subjects affected by gout or taking any antihyperuricemic agent or drugs able to interfere with the QT interval. A step-wise Cox regression analysis was used to determine the independent prognostic significance of age, gender, physical activity, smoking, body mass index (BMI), fasting plasma glucose, mean arterial pressure (MAP), heart rate, LDL-cholesterol, HDL-cholesterol, triglycerides, SUA and eGFR on ECG alterations during a 4-year follow-up. RESULTS No one of the considered variables was associated with the incident diagnosis of sinus tachycardia and sinus bradycardia. SUA predicted incident tachyarrhythmias, Q waves and ECG signs of left ventricular hypertrophy; age, female sex and active smoking predicted incident tachyarrhythmias; male sex, active smoking and LDL-cholesterol predicted incident ECG signs of previous myocardial infarction; BMI and MAP predicted incident ECG-diagnosed left ventricular hypertrophy. CONCLUSION In a cohort of general population, SUA seems to be a significant middle-term predictor of electrocardiographically diagnosed myocardial infarction, left ventricular hypertrophy and tachyarrhythmias.