Martina Rosticci

Association between serum uric acid, hypertension, vascular stiffness and subclinical atherosclerosis: data from the Brisighella Heart Study.

Objective: Serum uric acid (SUA) levels correlate with many recognized cardiovascular risk factors, including age, male sex, hypertension, diabetes mellitus, hypertriglyceridemia, obesity, and insulin resistance. The aim of our study was to verify in a large well characterized population sample the relationship between SUA values, hypertension, arterial stiffness and subclinical atherosclerosis. Methods: For this study, we selected 248 men and 371 women adult patients enrolled in the last Brisighella Heart Study population survey for which a full set of data were available and not consuming antihypertensive, antidiabetic, lipid-lowering and uric acid-lowering drugs. SUA and other available variables were related to blood pressure level, carotid-femoral pulse wave velocity (cfPWV) and carotid intima–media thickness (cIMT). Results: Hypertension prevalence was strongly related to SUA quartiles: we found significant differences between the 2nd (23.0%) and the 3rd quartiles (36.4%; P vs. 2nd < 0.05), and between the 3rd and the 4th quartile (56.3%; P vs. 3rd < 0.05). Similarly, the metabolic syndrome prevalence increased significantly at 39.5% in the 3rd SUA quartile (P < 0.05 vs. 2nd) and at 58.9% in the 4th quartile (P < 0.05 vs. 3rd). Intima–media thickness gradually and significantly rose along quartiles of SUA (P for trend < 0.0001), in particular, it was 0.86 mm in the 1st quartile, 0.90 in the 2nd, 0.94 in the 3rd, and 0.97 in the last quartile, with significant differences between each quartiles (all P < 0.05). In multivariate regression analyses, SUA resulted to be significantly associated to hypertension and metabolic syndrome prevalence, and IMT. Even if a significant association between SUA and cfPWV was found in univariate analysis (P = 0.002), when adjusting for age, the trend became nonsignificant (0.20). Conclusion: In the studied population sample, after adjustment for a large number of parameters, SUA appears to be significantly correlated to hypertension and IMT, but not to aortic stiffness.

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.

High serum uric acid is associated to poorly controlled blood pressure and higher arterial stiffness in hypertensive subjects

INTRODUCTION Serum uric acid (SUA) has been associated to incident hypertension and increased risk of cardiovascular diseases. MATERIALS AND METHODS Among the 2191 subjects enrolled during the last population survey of the Brisighella Heart Study, we identified 146 new cases of arterial hypertension and 394 treated but uncontrolled hypertensive patients with different levels of SUA. Their hemodynamic characteristics have been compared with those of age- and sex-matched normotensive (N. 324) and controlled hypertensive (N. 470) subjects. Then, by logistic regression analysis, we evaluated which factors were associated with a worse BP control under pharmacological treatment. RESULTS SUA levels were significantly higher in untreated hypertensive and uncontrolled hypertensive patients when compared to normotensives and controlled hypertensive patients. Pulse wave velocity (PWV) was significantly higher (p<0.001) in undiagnosed and uncontrolled hypertensive patients, while controlled hypertensive patients had PWV values comparable to normotensive controls. A similar trend has been observed for the augmentation index (AI). A worse BP control was associated with SUA levels (OR 1277, 95% CI 1134-1600 per mg/dL), AI (OR 1066, 95%CI 1041-1092 per unit), and PWV (OR 1201, 95% CI 1089-1423, per m/s), but not with age, body mass index, nor estimated glomerular filtration rate. CONCLUSION Based on our data, SUA seems to be associated with an inadequate BP control in subjects treated with antihypertensive drugs, and subjects with both uncontrolled BP and relatively high SUA levels have also an increased arterial stiffness that (per se) could be a cause of worse BP control under treatment.

Serum uric acid change and modification of blood pressure and fasting plasma glucose in an overall healthy population sample: data from the Brisighella heart study

Abstract Background: Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2 diabetes. It is less clear if changes in SUA are associated to different incidence in these main cardiovascular risk factors. Methods: From the cohort of the Brisighella Heart Study, we selected non-diabetic subjects that in 2008 were untreated with SUA-lowering drugs nor antihypertensive ones. Then we divided the subjects in four main groups: the ones that maintained their SUA level unchanged during the next 4 years, the ones that increased it >1 mg/dL without treatment, the ones that reduced it >1 mg/dL without drug treatment and the ones that reduced it >1 mg/dL with the continuous use of allopurinol. Results: Compared with 2008, SBP significantly increased in subjects with worsened (and untreated) SUA level, while improved in subjects treated with allopurinol (p < 0.05). In 2012, subjects with worsened (and untreated) SUA level had a significantly higher SBP compared with subjects with unchanged SUA and those with SUA improved after allopurinol treatment (p < 0.05). An identical trend has been observed as it regards FPG. Conclusion: It seems that SUA improvement could positively influence the age-related worsening of SBP and FPG in general population. Key messages Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2 diabetes. SUA improvement could positively influence the age-related worsening of SBP and FPG in general population.

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.

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.

Middle-Term Dietary Supplementation with Red Yeast Rice Plus Coenzyme Q10 Improves Lipid Pattern, Endothelial Reactivity and Arterial Stiffness in Moderately Hypercholesterolemic Subjects

Aim: The aim of our study was to investigate whether treatment with red yeast rice added with Coenzyme Q10 is associated with changes in endothelial function and arterial stiffness. Methods: This double blind, placebo-controlled, randomized clinical trial was carried out on 40 non-smoker moderately hypercholesterolemic subjects (ClinicalTrial.gov ID NCT02492464). After 4 weeks of diet and physical activity, patients were allocated to treatment with placebo or with an active product containing 10 mg monacolins and 30 mg Coenzyme Q10, to be assumed for 6 months. Endothelial reactivity and arterial stiffness have been measured through the validated Vicorder® device. Results: During monacolin treatment, patients experienced a more favorable percentage change in low density lipoprotein (LDL)-cholesterol (after monacolin treatment: -26.3%; after placebo treatment: +3.4%, p < 0.05). Endothelial reactivity (pulse volume displacement after monacolin treatment: +6.0%; after placebo treatment: -0.3%, p < 0.05), and arterial stiffness (pulse wave velocity (PWV) after monacolin treatment: -4.7%; after placebo: +1.1%, p < 0.05) also significantly improved only after monacolin treatment. Conclusion: The long-term assumption of the tested dietary supplement is associated with an improvement in LDL-cholesterolemia, endothelial reactivity and PWV in moderately hypercholesterolemic subjects.

Long-term predictors of impaired fasting glucose and type 2 diabetes in subjects with family history of type 2 diabetes: A 12-years follow-up of the Brisighella Heart Study historical cohort

AIM To identify and quantify the role of different risk factors in the long-term development of IFG and T2DM in a rural Italian population sample with family history of T2DM. METHODS We selected a sample of 1271 adult subjects from among those 1851 consecutively visited during four consecutive Brisighella Heart Study surveys (1996-2008), then selecting those ones with a family history of T2DM. Thus, we obtained a final sample including 545 subjects and for which a full clinical and ematochemistry data set was available. RESULTS The Cox-regression model better predicting the incident IFG and T2DM included age, gender, FPG, TG and SUA. The model best predicting the incident IFG status alone (without T2DM) is very similar to that predicting both IFG and T2DM, including the same predictors. Finally, the model best predicting T2DM (excluding IFG) simply includes FPG, BMI and ALT/AST ratio. Repeating the Cox-regression analysis using BMI as a covariate, TG appears to be also a significant predictor of T2DM (HR 1.018 95% CI 1.009-1.041, p=0.013). CONCLUSION In a sample of subjects with a family history of diabetes the best long-term predictors of IFG are age, gender, FPG, TG and SUA, while those of T2DM are FPG and BMI.

Circulating Levels of Proprotein Convertase Subtilisin/Kexin Type 9 and Arterial Stiffness in a Large Population Sample: Data From the Brisighella Heart Study

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulating levels are significantly associated with an increased risk of cardiovascular events. This study aimed to evaluate the relationship between circulating levels of PCSK9 and arterial stiffness, an early instrumental biomarker of cardiovascular disease risk, in a large sample of overall healthy participants. Methods and Results From the historical cohort of the Brisighella Heart Study, after exclusion of active smokers, participants in secondary prevention for cardiovascular disease, and patients in treatment with statins or vasodilating agents, we selected 227 premenopausal women and 193 age‐matched men and 460 postmenopausal women and 416 age‐matched men. In these participants, we evaluated the correlation between PCSK9 plasma circulating levels and pulse wave velocity. Postmenopausal women showed higher PCSK9 levels (309.9±84.1 ng/mL) compared with the other groups (P<0.001). Older men had significant higher levels than younger men (283.2±75.6 versus 260.9±80.4 ng/mL; P=0.008). In the whole sample, pulse wave velocity was predicted mainly by age (B=0.116, 95% CI 0.96–0.127, P<0.001), PCSK9 (B=0.014, 95% CI 0.011–0.016, P<0.001), and serum uric acid (B=0.313, 95% CI 0.024–0.391, P=0.026). Physical activity, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and estimated glomerular filtration rate were not associated with pulse wave velocity (P>0.05).By considering the subgroups described, age and PCSK9 levels were mainly associated with pulse wave velocity, which also correlated with serum uric acid in postmenopausal women. Conclusions In the Brisighella Heart Study cohort, circulating PCSK9 is significantly related to arterial stiffness, independent of sex and menopausal status in women.