Impact of simultaneous management of hypertension and hypercholesterolemia with ACE inhibitors and statins on cardiovascular outcomes in the Brisighella Heart Study: A 8-year follow-up.

BACKGROUND AND AIMS: To evaluate the long-term effect of simultaneous treatment of hypertension and hypercholesterolemia with angiotensin-converting enzyme (ACE) inhibitors and statins on the incidence of major cardiovascular events (MACE) and other clinical outcomes. METHODS AND RESULTS: We considered data from a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. We excluded normotensive subjects and individuals with a low calculated 10-year CVD risk, hypertensive patients treated with antihypertensive drugs different from ACE inhibitors and patients who changed antihypertensive medications during follow-up. The remaining participants were divided into four groups depending on whether they were treated with (I) perindopril ± amlodipine without statin treatment (N. 132), (II) perindopril ± amlodipine and atorvastatin (N. 132), (III) an ACE inhibitor other than perindopril ± a calcium-channel blocker without statin therapy (N. 133), (IV) an ACE inhibitor other than perindopril ± a calcium-channel blocker and statin therapy (N. 145). The long-term (8 years) effects of the different combined treatment were compared among the pre-defined groups. Over the follow-up period of 8 years, the proportion of subjects who developed MACE, type 2 diabetes mellitus and hyperuricemia, and the proportion of subjects needing for the intensification of antihypertensive treatment to improve blood pressure control were statistically different among the predefined groups (P < 0.05). CONCLUSION: Combined treatment with ACE inhibitors and statins (especially atorvastatin) in hypertensive patients seems to significantly reduce the risk of developing CVD in comparison with treatment with ACE inhibitors alone.

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.

Controlled co-deposition of FePt nanoparticles embedded in MgO: a detailed investigation of structure and electronic and magnetic properties.

Films of FePt nanoparticles (NPs) embedded in MgO were obtained by controlled co-deposition of FePt NPs pre-formed by a gas aggregation source and of Mg evaporated in an oxygen atmosphere. Assemblies of core-shell FePt@MgO NPs and films of FePt NPs embedded in MgO matrix could be obtained by varying FePt and Mg deposition rates. Transmission electron microscopy (TEM) and high resolution-TEM revealed the core-shell structure of the NPs, with an FePt core (of average diameter (d) = 4.75 nm) presenting a multitwinned icosahedral structure, and MgO partially in crystalline form. The functional effect of the MgO shell in shielding the FePt core from external oxidation was shown with XPS. Upon controlled annealing, a transition from A1 to L10 ordering could be obtained, with structural and morphological re-arrangement. The magnetic hysteresis loops obtained from alternating gradient field magnetometry at room temperature show a 'wasp-waist' shape, with small values of coercive field (Hc = 300-1400 Oe), decreasing at increasing amounts of co-deposited MgO.

VO2 kinetics in supra-anaerobic threshold constant tests allow the visualization and quantification of the O2 saving after cytochrome c oxidase inhibition by aerobic training or nitrate administration.

We tested whether the known cytochrome c oxidase (COX) inhibition by nitric oxide (NO) could be quantified by VO(2) kinetics during constant load supra-Anaerobic Threshold (AT) exercises in healthy trained or untrained subjects following aerobic training or nitrate administration. In cycle ergometer constant load exercises supra-AT, identified in previous incremental tests, VO(2) kinetics describe a double exponential curve, one rapid and one appreciably slower, allowing the area between them to be calculate in O(2) l. After training, with increased NO availability, this area decreases in inverse ratio to treatment efficacy. In fact, in 11 healthy subjects after aerobic training for 6-7 weeks, area was decreased on average by 51 %. In 11 untrained subjects, following the assumption of an NO donor, 20 mg isosorbide 5 mononitrate, area was decreased on average by 53 %. In conclusion, supra-AT VO(2) kinetics in constant load exercises permit the quantification of the inhibitory effect NO-dependent on COX after either physical training or nitrate assumption.

Structure and stability of nickel/nickel oxide core-shell nanoparticles.

The results of a combined x-ray photoelectron spectroscopy (XPS) and high resolution transmission electron microscopy (HR-TEM) study of Ni nanoparticles (NP), before and after oxidation, are presented. An experimental set-up was realized for the preparation and study of pre-formed NP films, concentrating the attention on Ni NP in the diameter range between 4 and 8 nm. The XPS data were taken in situ from NPs after different stages of oxidation, including controlled dosing of O(2) gas in the experimental system and exposure to the atmosphere. The Ni 2p structure is a combination of spectra from metallic Ni in the NP core and from the oxide shell. The signal from the NP core was observed even for samples after exposure to air. From the comparison of HR-TEM experimental images with theoretical simulations, it was found that the Ni NP core has a regular multitwinned icosahedral structure, composed of single-crystal tetrahedra with (111) faces. The NiO phase is clearly observed forming islands on the NP surface.

Influence of lifestyle measures on hypertriglyceridaemia.

Hypertriglyceridaemia is a common dyslipidaemia encountered in clinical practice. People with hypertriglyceridaemia are frequently obese, insulin-resistant, hypertensive or diabetic, all of which are risk factors for cardiovascular diseases. Hypertriglyceridaemia also contributes to metabolic syndrome, in which an atherogenic diet, sedentary lifestyle, overweight/obesity and genetic factors interact. A multi-factorial intervention for all risk factors is necessary, including weight reduction, dietary modification and increased physical exercise. This review focuses on the influence of diet, sedentary lifestyle and negative habits (such as excessive alcohol intake, smoking and drug addiction) on hypertriglyceridaemia as well as the effects of lifestyle change.

Relative role of major risk factors for Type 2 diabetes development in the historical cohort of the Brisighella Heart Study: an 8-year follow-up.

AIM: The aim of this study was to evaluate and quantify the role of different risk factors in the long-term development of Type 2 diabetes mellitus in a rural Italian population. METHODS: The Brisighella Heart Study (BHS; 1972-2003) is a prospective, population-based longitudinal epidemiological cohort involving 2939 randomly selected subjects, aged 14-84 years, resident in the rural Italian town of Brisighella. For this study, we randomly selected 1441 adult subjects representative of the Brisighella population; consecutively visited during three BHS surveys. A step-wise Cox regression analysis determined the prognostic significance of each independent risk factor for the development of Type 2 diabetes in the 8-year long follow-up. RESULTS: Blood pressure, high-density lipoprotein cholesterol, triglycerides, physical activity, total energy intake, and drug treatment had no effect on the incidence of diabetes. Age was a significant predictor of Type 2 diabetes when inserted alone in the model (P = 0.007), but irrelevant when adjusted for baseline body mass index (BMI) and or fasting plasma glucose. Among these with impaired fasting glucose (IFG), the diabetes incidence/year was estimated to be 6.6% for men and 11.2% for women (P < 0.001). Basal glycaemia under 6.1 mmol/l were not significant long-term predictors of diabetes development, while higher basal glycaemia and each level BMI were. CONCLUSION: Our findings confirm that IFG and BMI predict Type 2 diabetes development in our population. This should help to identify effective approaches to prevention.

Trends in blood pressure control and antihypertensive treatment in clinical practice: the Brisighella Heart Study.

OBJECTIVES: To assess trends in blood pressure (BP) awareness, control, treatment and use of different antihypertensive medications in a cohort of hypertensive patients. DESIGN: This study summarizes the results of a 12-year observation (1984-1996) of a cohort of 940 hypertensive patients from the population of 2329 participants to the Brisighella Heart Study (BHS). Primary outcome measures were the extent of BP control (systolic/diastolic BP < 140/90 mmHg) and prevalence of the use of various antihypertensive medications. RESULTS: From 1984 to 1996 the proportion of patients aware of elevated BP and treated for hypertension rose from 73 to 88% and from 43.8 to 50.3% in men, and from 77 to 87% and from 50 to 56.6% in women (P < 0.001 for all). The rate of BP control increased from 7.5 to 17.4% in men (P < 0.001) and from 7.3 to 18.5% in women (P < 0.001). This occurred with increased use of combination therapy (+0.2 drugs/person) and with a decline in the use of diuretics (-38.2% men and -28% women; P < 0.001) and an increase in use of calcium-channel blockers (CCBs) (24.2% in men and 12.2% in women; P < 0.001) and angiotensin-converting enzyme (ACE) inhibitors (30.7% in men and 30.8% in women; P < 0.001) as first-line drugs. The improved BP control was associated with a lower rate of fatal and non-fatal cardiovascular (CV) events. CONCLUSIONS: The results of this observational study confirm that the rate of BP control can be improved in daily clinical practice by increasing the use of drug combinations, as well as by the first-line prescription of ACE inhibitors and CCBs [and probably angiotensin II receptor inhibitors (ARBs)].

The realization of a project aimed at reducing the plasmatic lipid level in a large Italian population improves the mean calcium daily intake: the Brisighella Study.

OBJECTIVES: Evaluation of the impact of a coronary heart disease prevention program on calcium, magnesium, phosphorus and vitamin D dietary intake in respect of recommended daily allowances in a large Italian rural population. DESIGN: Retrospective analysis of the Brisighella Study dietary data. The Brisighella Study started in 1972 as a longitudinal study on atherosclerosis risk factors. SETTING: Brisighella, a rural North Italian village. SUBJECTS: The Brisighella population's dietary habits were monitored from 1980 every 4 h through a dietary record sheet. 1,350 constantly tested subjects were subdivided according to NHI Consensus Conference on Calcium RDA. INTERVENTION: In 1986, the studied subjects were invited to reduce their consumption of animal fats and cholesterol through a Nutrition Educational Program (NEP). RESULTS: Before NEP, calcium intake was low in each sex and age category: 20-40% of the populatioin had a daily intake < 550 mg. In 1988, among the 1350 subjects who constantly completed the questionnaire (M = 651, F = 699), the mean calcium intake significantly rose in all age categories: M = 1,003 (25-65 y) and 877 ( > 65) mg/24h (P < 0.001 vs 1984); F = 923 (25-50), 860 (51-65) and 767 (> 65)mg/24h (P < 0.05). In 1992, 3y after the NEP conclusion, calcium intake dropped in each sex and age category. The NEP influenced vitamin D, phosphorus and magnesium intakes less. CONCLUSIONS: A collective NEP aimed at lowering saturated fats and cholesterol intakes, improves the calcium intake; in order to maintain their efficacy on nutritional habit changes, these programs must become an ongoing item.

A suggestion for familial hypercholesterolemia (FH) heterozygosity clinical diagnosis based on epidemiological observations in a large Italian population.

We selected 247 subjects from 29 large familial hypercholesterolemia (FH) kindreds from 550 probable FH subjects in Emilia Romagna (Italy) on the basis of LDL-cholesterol plasmatic levels and family trees, in order to define the best diagnostic criteria for heterozygous patients. Familial hypercholesterolemia is a monogenic disease of cholesterol metabolism inherited as an autosomal dominant trait and characterised by early cardiovascular disease. A low xanthomas and xanthelasmas prevalence was found (8.6%); coronary heart disease (CHD) death occurs very frequently in heterozygous males (72% of all deaths; mean age at death 52 years), while in females the primary cause of death was thrombotic stroke (55%; mean age 69 years). Total cholesterol (TC) mean values were 389.8 (m) and 373.3 mg/dl (f) for FH trait carriers, and 223.3 (m) and 228.8 (f) for healthy relatives. No age-related change in TC was found in heterozygotes, while unaffected relatives of FH families showed mean TC and LDL-C values, and a TC frequency distribution and a TC age-related increasing trend similar to the expected values for the Italian population. The TC frequency distribution curve appeared bimodal, with a mid-point between heterozygous and homozygous FH modal values of 280 mg/dl. To identify the FH patients, the final FH heterozygosity risk was evaluated in an unselected free-living population (from 0.07 to 0.8%, respectively, for TC between 265-274 and 295-304 mg/dl) and in hypercholesterolemic families (31 to 83%, and the same TC classes). Our conclusion is that the clinical picture is rarely pathognomonic, while the FH heterozygosity final risk evaluation and the 280 mg/dl cut-off point can be used to guide the practical clinical diagnosis and to select the patients destined for B-E receptor activity evaluation.

Hemopoiesis in healthy old people and centenarians: well-maintained responsiveness of CD34+ cells to hemopoietic growth factors and remodeling of cytokine network.

In vitro hemopoiesis and hemopoietic cytokines production were evaluated in 9 centenarians (median age 100.5 years, age range: 100-104 years), 10 old people (median age: 71 years, age range: 66-73 years), and 10 young people (median age: 35 years, age range: 30-45 years), all carefully selected for their healthy status. The main findings were the following: (i) a trend towards a decreased absolute number of CD34+ progenitor cells in the peripheral blood of old people and centenarians, in comparison to young subjects; (ii) a well-preserved capability of CD34+ cells from old people and centenarians to respond to hemopoietic cytokines, and to form erythroid (BFU-E), granulocyte-macrophagic (CFU-GM), and mixed colonies (CFU-GEMM) in a way (number, size, and morphology) indistinguishable from that of young subjects; (iii) an age-related decreased in vitro production of granulocyte-macrophagic colony-stimulating factor (GM-CSF) and a decreased production of interleukin-3 (IL-3) in centenarians by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC); (iv) a linear increase of the serum level of stem cell factor (SCF), measured in the above-mentioned subjects and in 65 additional subjects, including 4 centenarians. These data suggest that basal hematopoietic potential is well preserved in healthy centenarians, and that the hemopoietic cytokine network undergoes a complex remodeling with age.

Age-related modifications of the human alphabeta T cell repertoire due to different clonal expansions in the CD4+ and CD8+ subsets.

We have studied the effects of a life-long antigen stimulation on the clonal heterogeneity of human peripheral T cell subsets, as defined by their CD45 isoform expression. CD4+ or CD8+ T cells were obtained from healthy donors ranging in age from 20 to 100 years, and sorted into CD45RA+ and CD45RO+ populations. A modified PCR-heteroduplex analysis was then used to directly compare the TCR Vbeta clonal make up of either compartment pair. We find that the CD4+ T cell repertoire remains largely polyclonal throughout life, since CD4+ expanded clones are rare and accumulate predominantly in the CD45RO+ compartment of exceptionally old donors (100 years old). In contrast, the CD8+ T cell subset contains expanded clones which are already detectable in young adults and become very frequent in 70- to 75-year-old donors in both CD45RA+ and CD45RO+ compartments analyzed. Interestingly, some expanded clones are detectable in the CD45RA+ or in both CD45RA+ and CD45RO+ compartments of either CD4+ or CD8+ T cells. These results indicate that the age-dependent accumulation of expanded clones starts earlier and is more pronounced in the CD8+ than in the CD4+ T cell subset, reinforcing the concept that clonal expansion in the two subsets is controlled by substantially different mechanisms. Furthermore, whereas the finding of expanded CD45RO+ T cell clones is explained by antigen-driven proliferation, the detection of expanded clones in the CD45RA+ or in both CD45RA+ and CD45RO+ compartments would support the hypothesis of reversion from the CD45RO+ to the CD45RA+ phenotype after antigen encounter.

Cardiovascular disease and Lp(a) in the adult population and in the elderly: the Brisighella study.

OBJECTIVE: The aim of this study was to evaluate the distribution of the concentrations of lipoprotein(a) [Lp(a)] in a free-living population, that of Brisighella, and to study the degree of association with cardiovascular disease (CVD) and other associated risk factors. The Brisighella study is included in the framework of observational and interventional longitudinal studies; it began in 1972 to monitor the spontaneous trend of the risk factors for atherosclerosis and to evaluate the incidence of CVD in a rural population. METHODS: The studies were carried out on 1319 subjects, 627 males and 692 females, aged over 14 years, of which 134 men and 113 women were geriatric (age > 64 years); the data are relative to the control of the population in 1988. The following were evaluated for each subject: (a) weight and height; (b) hematological parameters; (c) clinical events; (d) presence of other concomitant diseases. For the dosage of the hematological parameters, enzymatic-colorimetric parameters were used (total and HDL cholesterol, triglycerides, glycemia and uremia), radial immunodiffusion and immunoturbidimetry (apoAI and B), ELISA-sandwich immunoenzymatic method (Lp(a)). All the methods used are standardized and internal and external laboratory quality control was carried out. The data collected were analyzed with the program STATGRAPHIC VERSION 6.0; the mean, the standard deviation and the median were calculated for all the variables. The frequency tables, distribution curves (approximation estimates with the chi 2 test), and single and multiple regression were also calculated. A value of p < 0.01 was taken as the level of significance. RESULTS: The distribution of Lp(a) in the control population and in subjects with CVD was substantially the same for both sexes; the differences between the mean levels of Lp(a) were not statistically significant (18.5 mg/dl vs 20.09 mg/dl for men and 19.98 mg/dl vs 22.78 mg/dl for women). The same also applies to the elderly population (18.81 mg/dl vs 23.31 in the men and 21.13 mg/dl vs 21.47 mg/dl in the women). No significant variations were observed in the mean values of Lp(a) even when other risk factors were taken into consideration, such as hypertension, obesity and diabetes. Finally, multiple regression analysis did not show any correlation between Lp(a) levels and those of the other hematological parameters. CONCLUSIONS: In this transversal study, we found no evidence to suggest that Lp(a) can be considered and independent and predictive risk factor for CVD. It would therefore seem that in the population of Brisighella the levels of Lp(a) are "causally" distributed, without any correlation with the presence of cardiovascular events or with hypertension, diabetes or obesity in both sexes.

Total cholesterol, high-density lipoprotein cholesterol, and triglycerides in children receiving antiepileptic drugs.

The influence of antiepileptic drug (AED) therapy on total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides was studied in 208 epileptic children compared with 175 normal children. A significant increase in TC plasma levels was observed with carbamazepine (CBZ), phenobarbital (PB), and phenytoin (PHT). The patients receiving valproate (VPA) showed levels very similar to those of the control population. The results may be explainable by the different biotransformation pathway of these drugs. HDL cholesterol and triglycerides were not altered by any of the AEDs. We recommend monitoring TC level in patients receiving CBZ, PB, and PHT and prescription of diet treatment, at least during the time of AED treatment.