Maddalena Veronesi

Surgical Menopause Increases Salt Sensitivity of Blood Pressure

Salt sensitivity of blood pressure is associated with an elevated risk of developing hypertension (HTN) and is an independent risk factor for cardiovascular disease. The prevalence of HTN increases after menopause. The aim of this study was to investigate prospectively whether the loss of ovarian hormones increases the occurrence of salt sensitivity among healthy premenopausal women. We enrolled 40 normotensive, nondiabetic women (age 47.2±3.5), undergoing hysterectomy–oophorectomy for nonneoplastic processes and not on hormone replacement, to determine the effect of changes in sodium intake on blood pressure the day before and subsequently 4 months after surgical menopause. Salt loading was achieved using a 2-L normal saline infusion and salt depletion produced by 40 mg of intravenous furosemide. A decrease >10 mm Hg in systolic blood pressure between salt loading and salt depletion was used to define salt sensitivity. Before and after menopause, salt-sensitive women exhibited higher waist/hip and waist/thigh ratios (P<0.01). Although all of the women remained normotensive, the prevalence of salt sensitivity was significantly higher after surgical menopause (21 women; 52.5%) than before (9 women; 22.5%; P=0.01), because 12 (38.7%) salt-resistant women developed salt sensitivity after menopause. In summary, we demonstrated that the prevalence of salt sensitivity doubled as early as 4 months after surgical menopause, without an associated increase in blood pressure. Epidemiological studies indicate that development of HTN may not occur until 5 to 10 years after menopause. The loss of ovarian hormones may unmask a population of women prone to salt sensitivity who, with aging, would be at higher risk for the subsequent development of HTN and cardiovascular disease.

Use of lipid-lowering drugs and blood pressure control in patients with arterial hypertension.

A large proportion of patients have both hypertension and hypercholesterolemia, two of the most important risk factors for cardiovascular diseases. Statins are the most widely used drugs for the treatment of plasma lipid abnormalities and have been reported to interact with elevated blood pressure. A reduction in blood pressure associated with the use of these agents has been reported in patients with untreated hypertension and in patients treated with antihypertensive drugs, particularly angiotensin‐converting enzyme inhibitors and calcium channel blockers. This effect on blood pressure control has also been observed in diabetic patients. The mechanism responsible for the hypotensive effect seems to be largely independent of the effect of statins on plasma cholesterol, and probably is related to the interaction of the medications with endothelial function or angiotensin II receptors. The capacity of statins to improve blood pressure control may represent a useful tool for improvement in the prevention of cardiovascular diseases.

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.

Interaction between serum cholesterol levels and the renin-angiotensin system on the new onset of arterial hypertension in subjects with high-normal blood pressure.

Objectives To investigate the possible interactions between serum cholesterol levels and the renin–angiotensin system on the development of stable hypertension in subjects with high-normal blood pressure (BP). Background Hypercholesterolemia increases angiotensin-II type 1 (AT1) receptor density and pressor responsiveness to angiotensin II, and has been reported to contribute to the development of hypertension. The effects of elevated serum cholesterol levels on BP control might be exaggerated by concomitant activation of the renin–angiotensin system, and their combination might contribute to the development of stable hypertension. Methods We investigated the relationship between serum cholesterol levels, plasma renin activity (PRA) and the long-term development of hypertension in 66 young (age < 45 years) patients with high-normal BP and elevated (> 200 mg/dl, n = 46: HC) or normal (≤200 mg/dl, n = 20: NC) serum cholesterol levels and in 20 normotensive, normocholesterolemic controls (C). The main outcome measure was the prospective evaluation of the 15-year incidence of stable hypertension in the different populations. Results New-onset hypertension was higher in patients with high-normal BP and HC when compared to NC patients [relative risk (RR) = 1.9; 95% confidence interval (CI), 1.1–4.3, P < 0.001] and control subjects (RR = 3.1; 95% CI = 1.4–5.3, P < 0.001). High PRA increased the overall rate of hypertension in both HC and NC. The interaction between HC and PRA was more evident in patients with borderline high cholesterol levels (200–240 mg/dl) where the adjusted relative risk of new onset of hypertension was 2.17 (95% CI 1.2–3.74; P < 0.05) in high PRA subjects and 1.17 (95% CI 0.67–2.23; P = 0.87) in subjects with normal PRA. Conclusion We support the hypothesis that the presence of hypercholesterolemia can promote the development of stable hypertension through its interaction with the circulating renin–angiotensin system in patients with high-normal blood pressure.

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.

Relationship between blood pressure, cholesterolemia and serum apolipoprotein B in a large population sample: the Brisighella Heart Study.

Objective: The objective is to evaluate the relationship between cholesterolemia, serum apolipoprotein B (apoB) level and blood pressure in a large sample of general population. Methods: The Brisighella Heart Study (BHS) is a prospective, population-based longitudinal epidemiological investigation. For this study, we analysed the data sampled in the 2008 BHS population survey, excluding those participants treated with antihypertensive and/or lipid lowering drugs (N: 2473). Results: In a sex, BMI, smoking habit, physical activity level and serum creatinine adjusted model, low-density lipoprotein-cholesterol (LDL-C) appears to be significantly related to SBP (P < 0.001), DBP (P = 0.026), and pulse pressure (PP) (P < 0.001). In individuals aged less than 52 years, LDL-C was significantly associated to SBP and DBP (P < 0.001), but not PP. In the same model, apoB appears to be mildly but significantly related to SBP (P < 0.001), DBP (P < 0.001), and PP (P < 0.001). In individuals aged less than 52 years, apoB was significantly associated to SBP (P < 0.001), DBP (P < 0.001), and PP (P < 0.001). In individuals aged 52 or more, nor LDL-C neither apoB were significantly associated to blood pressure. Including in the same model LDL-C and apoB, apoB excluded the predicting role of LDL-C as it regards the blood pressure either in the whole population sample and in the younger individuals. Conclusion: On the basis of our observation, either serum LDL-C and apoB are significantly related to the blood pressure level in a large sample of individuals untreated with antihypertensive and lipid-lowering drugs. This association is stronger in younger individuals than in elderly. ApoB seems to be a stronger predictor of either SBP, DBP and PP than LDL-C.

Persistence on Treatment and Blood Pressure Control with Different First-Line Antihypertensive Treatments: A Prospective Evaluation

We enrolled 347 hypertensive patients, randomly allocated them to different first-line treatments, and followed-up for 24 months. Persistence on treatment was significantly higher in patients treated with ARBs (68.5%) and ACE inhibitors (64.5%) vs. CCBs (51.6%), β-blockers (44.8%), and diuretics (34.4%). No ARB, ACE inhibitor, β-blocker, or diuretic was associated with a greater persistence in therapy as compared with the other molecules used in each therapeutic class. The rate of persistence was significantly higher in patients treated with lercanidipine vs. other CCBs (59.3% vs. 46.6%). Systolic and diastolic BP decreased more in patients treated with ARBs (-11.2/-5.8 mmHg), ACE inhibitors (-10.5/-5.1 mmHg), and CCBs (-8.5/-4.6 mmHg) when compared to ß-blockers (-4.0/-2.3 mmHg) and diuretics (-2.3/-2.1 mmHg).

Tinnitus in elderly patients and prognosis of mild-to-moderate congestive heart failure: a cross-sectional study with a long-term extension of the clinical follow-up

BackgroundThe complex mechanism responsible for tinnitus, a symptom highly prevalent in elderly patients, could involve an impaired control of the microcirculation of the inner ear, particularly in patients with poor blood pressure control and impaired left ventricular (LV) function.MethodsIn order to define the relationship between the presence of tinnitus and the severity and clinical prognosis of mild-to-moderate chronic heart failure (CHF) in a large population of elderly patients (N = 958), a cross-sectional study was conducted with a long-term extension of the clinical follow-up. Blood pressure, echocardiographic parameters, brain natriuretic peptide (BNP), hospitalization, and mortality for CHF were measured. Multivariate logistic regression analysis was used to assess the association between the presence of tinnitus and some of the prognostic determinants of heart failure.ResultsThe presence of tinnitus was ascertained in 233 patients (24.3%; mean age 74.9 ± 6 years) and was associated with reduced systolic and diastolic blood pressure (123.1 ± 16/67.8 ± 9 vs 125.9 ± 15/69.7 ± 9; P = .027/P = .006), reduced LV ejection fraction (LVEF%; 43.6 ± 15 vs 47.9 ± 14%, P = .001), and increased BNP plasma levels (413.1 ± 480 vs 286.2 ± 357, P = .013) in comparison to patients without symptoms. The distribution of CHF functional class was shifted toward a greater severity of the disease in patients with tinnitus. Combined one-year mortality and hospitalization for CHF (events/year) was 1.43 ± 0.2 in patients with tinnitus and 0.83 ± 0.1 in patients without tinnitus, with an adjusted hazard ratio (HR) of 0.61 (95% confidence interval (CI): 0.37 to 0.93, P <.002).ConclusionsOur preliminary data indirectly support the hypothesis that tinnitus is associated with a worse CHF control in elderly patients and can have some important clinical implications for the early identification of patients who deserve a more aggressive management of CHF.

Prospective evaluation of the effect of statins on blood pressure control in hypertensive patients in clinical practise

BACKGROUND AND AIM Some clinical evidence supports a statin antihypertensive effect. Our aim is to evaluate the statin effect on blood pressure control in hypertensive patients in the setting of clinical practice, and the role of some predetermined individual patient characteristics (age, gender, baseline BP levels, pre-treatment LDL-C levels) on the supposed statin BP lowering effect. METHODS AND RESULTS Two hundred and fifty-four hypertensive patients with hypercholesterolemia were enrolled in the Ambulatory service of the Hypertension Research Unit of Bologna University Hospital. After 2-4 weeks of a run-in period patients were allocated to statin treatment and followed-up for 24 weeks. The blood pressure response to statins was compared in several subgroups of patients according to age, gender, baseline BP and pre-treatment cholesterolemia. In the overall study population, the use of statins was associated with a significant reduction in systolic (-7.6+/-4 mmHg, p<0.05) and diastolic blood pressures (-5.2+/-3 mmHg, p<0.05) in comparison to baseline. The blood pressure decrease was more pronounced in patients younger than 65 years (p<0.05), with higher baseline systolic blood pressure (p<0.005), and in those with higher cholesterolemia before statins (p<0.05). CONCLUSIONS Our study suggests a BP-lowering effect of statins, consistent with some other literature. Some parameters like age, baseline systolic blood pressure and cholesterolemia influence the antihypertensive effect of statins. The lack of consideration for these confounding factors may be one of the reasons for the conflicting results about the BP lowering effects of statins.

An evidence-based review on urate-lowering treatments: implications for optimal treatment of chronic hyperuricemia

Several studies suggest that chronic hyperuricemia, the main precursor of gout, is involved in the pathogenesis of different systemic disorders that affect cardiovascular and renal systems, such as hypertension, obesity, hypercholesterolemia, atherosclerosis, metabolic syndrome, chronic heart failure, and chronic kidney disease. Recent epidemiological evidence has shown an increasing trend in the prevalence of hyperuricemia and gout in the Western world: a number of population-based studies estimate a prevalence of up to 21% for hyperuricemia and 1%–4% for gout. As such, early detection and careful management of this pathological condition is required, starting from lifestyle changes (mainly based on a diet low in red meat, sugars, and alcoholic beverages, with increased intake of vegetables, water, and vitamin C sources), adding specific drugs to lead serum uric acid (SUA) levels under the target value of 7 mg/dL. In particular, nonselective and selective XO inhibitors (allopurinol, oxypurinol, febuxostat) reduce SUA levels and the overproduction of reactive oxygen species, mainly related to XO overactivity that often causes inflammatory damage to the vascular endothelium. The effect of lowering SUA levels via XO inhibition includes an attenuation of oxidative stress and related endothelial dysfunction that largely contribute to the pathophysiology of metabolic syndrome and cardiovascular diseases. Therefore, the inhibition of XO overactivation seems to be an excellent therapeutic option to limit the harmful effects of excess UA and reactive oxygen species. In conclusion, rapid diagnosis and correct therapy for hyperuricemia may also improve the prevention and/or treatment of serious and multifactorial diseases. The available evidence supports the importance of promoting new experimental clinical trials to confirm the emerging antioxidant role of XO inhibitors, which could effectively contribute to cardiovascular and chronic kidney disease prevention.