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The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis. [ABSTRACT FROM AUTHOR]

Overweight clusters with high blood pressure (BP), but the independent contribution of both risk factors remains insufficiently documented. In a prospective population study involving 8467 participants (mean age 54.6 years; 47.0% women) randomly recruited from 10 populations, we studied the contribution of body mass index (BMI) to risk over and beyond BP, taking advantage of the superiority of ambulatory over conventional BP. Over 10.6 years (median), 1271 participants (15.0%) died and 1092 (12.9%), 637 (7.5%) and 443 (5.2%) experienced a fatal or nonfatal cardiovascular, cardiac or cerebrovascular event. Adjusted for sex and age, low BMI (<20.7 kg m−2) predicted death (hazard ratio (HR) vs average risk, 1.52; P<0.0001) and high BMI (⩾30.9 kg m−2) predicted the cardiovascular end point (HR, 1.27; P=0.006). With adjustments including 24-h systolic BP, these HRs were 1.50 (P<0.001) and 0.98 (P=0.91), respectively. Across quartiles of the BMI distribution, 24-h and nighttime systolic BP predicted every end point (1.13⩽standardized HR ⩽1.67; 0.046 ⩽P<0.0001). The interaction between systolic BP and BMI was nonsignificant (P⩾0.22). Excluding smokers removed the contribution of BMI categories to the prediction of mortality. In conclusion, BMI only adds to BP in risk stratification for mortality but not for cardiovascular outcomes. Smoking probably explains the association between increased mortality and low BMI. [ABSTRACT FROM AUTHOR]

Previous studies of cases and controls or selected patients demonstrated association of the ADRB1 Arg389Gfy and ADRA2B I/D polymorphisms with blood pressure, measures of obesity, and/or serum lipidia. In multivariate-adjusted analyses of 1881 subjects randomly recruited from a White population, ADRBl ArgArg homozygotes, compared with Gly alíele carriers, had higher diastolic blood pressure (79.4 vs 78.4mmHg; P=0.012), and higher serum high-density lipoprotein (HDL) cholesterol (1.33 vs l^mmoU"1; P = 0.020), whereas none of the other cardiovascular or metabolic phenotypes reached significance in relation to the two polymorphisms. Our family-based design excluded population stratification as a possible explanation for the significant association of the ADRBl Arg389Gly polymorphism with blood pressure and HDL cholesterol. [ABSTRACT FROM AUTHOR]

The classification of arterial hypertension (HT) to define metabolic syndrome (MS) is unclear in that different cutoffs of blood pressure (BP) have been proposed. We evaluated the categorization of HT most qualified to define MS in relationship with coronary heart disease (CHD) mortality at a population level. A total of 3257 subjects aged 65 years were followed up for 12 years. MS was defined according to the criteria of the National Education Cholesterol Program using three different categories of HT: MS-1 (systolic blood pressure (SBP) 130 and diastolic blood pressure (DBP) 85 mm Hg), MS-2 (SBP 130 or DBP 85 mm Hg) and MS-3 (pulse pressure (PP) 75 mm Hg in men and 80 mm Hg in women). Gender-specific adjusted hazard ratio (HR) with 95% confidence intervals (CI) for CHD mortality was derived from Cox analysis in the three MS groups, both including and excluding antihypertensive treatment. In women with MS untreated for HT, the risk of CHD mortality was always significantly higher than in those without MS, independent of categorization; the HR of MS was 1.73 (CI 1.12–2.67) using MS-1, 1.75 (CI 1.10–2.83) using MS-2 and 2.39 (CI 3.71–1.31) using MS-3. In women with MS treated for HT, the HR of CHD mortality was significantly increased only in the MS-3 group (1.92, CI 1.1–2.88). MS did not predict CHD in men. In conclusion, MS can predict CHD mortality in elderly women with untreated HT but not in those with treated HT; in the latter, PP is the most predictive BP value.Journal of Human Hypertension (2007) 21, 934–941; doi:10.1038/sj.jhh.1002245; published online 14 June 2007 [ABSTRACT FROM AUTHOR]

The relationship between serum uric acid (SUA) and risk of coronary heart disease (CHD) mortality remains controversial, particularly in diabetic subjects. The aim of the present study is to evaluate whether SUA independently predicts CHD mortality in non-insulin-dependent elderly people from the general population and to investigate the interactions between SUA and other risk factors. Five hundred and eighty-one subjects aged ≥65 years with non-insulin-dependent diabetes mellitus were prospectively studied in the frame of the CArdiovascular STudy in the ELderly (CASTEL). Historical and clinical data, blood tests and 12-year fatal events were recorded. SUA as a continuous item was divided into tertiles and, for each tertile, adjusted relative risk (RR) with 95% confidence intervals (CI) was derived from multivariate Cox analysis. CHD mortality was predicted by SUA in a J-shaped manner. Mortality rate was 7.9% (RR 1.28, CI 1.05–1.72), 6.0% (reference tertile) and 12.1% (RR 1.76, CI 1.18–2.27) in the increasing tertiles of SUA, respectively, without any difference between genders. In diabetic elderly subjects, SUA independently predicts the risk of CHD mortality in a J-shaped manner. [ABSTRACT FROM AUTHOR]

Genetic variability in the ADD1 (Gly460Trp) and ADD2 (C1797T) subunits of the cytoskeleton protein adducin plays a role in the pathogenesis of hypertension, possibly via changes in intracellular cation concentrations. ADD2 1797CC homozygous men have decreased erythrocyte count and hematocrit. We investigated possible association between intra-erythrocyte cations and the adducin polymorphisms. In 259 subjects (mean age 47.7 years), we measured intra-erythrocyte Na+ [iNa], K+ [iK] and Mg2+ [iMg], serum cations and adducin genotypes. Genotype frequencies (ADD1: GlyGly 61.5%, Trp 38.5%; ADD2: CC 80.4%, T 19.6%) complied with Hardy–Weinberg proportions. In men, ADD2 CC homozygotes (n=100) compared to T-carriers (n=23) had slightly lower iK (85.8 versus 87.5 mmol/l cells; P=0.107), higher iMg (1.92 versus 1.80 mmol/l cells; P=0.012), but similar iNa (6.86 versus 6.88 mmol/l cells; P=0.93). In men, iK, iMg and iNa did not differ according to ADD1 genotypes. In men, iK (R2=0.128) increased with age and serum Na+, but decreased with serum total calcium and the daily intake of alcohol. iMg (R2=0.087) decreased with age, but increased with serum total calcium. After adjustment for these covariates (P0.04 for all), findings in men for iK (CC versus T: 85.8 versus 87.3 mmol/l; P=0.14) and iMg (1.91 versus 1.82 mmol/l; P=0.03) remained consistent. In 136 women, none of the phenotype–genotype relations reached significance. Changes in intra-erythrocyte cations in ADD2 1797CC homozygous men might lead to osmotic fragility of erythrocytes, but to what extent they reflect systemic changes or are possibly involved in blood pressure regulation remains unknown.Journal of Human Hypertension (2007) 21, 387–392. doi:10.1038/sj.jhh.1002154; published online 15 February 2007 [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate risk pattern and mortality in a general population epidemiologic study performed by a staff of hypertension specialists working as the "good father of a family," with lifestyle and therapeutic advice and instrumental measurements. Mortality among the study population (n=856) during the 4-y study was compared with that recorded in the general population during the 4-y period before the study; those who refused to participate in the study were also recorded (n=280). Among study subjects, blood pressure decreased by 3.6/3.5 mm Hg (P<.01/P<.0001), serum total cholesterol by 3.8% (P<.0001), and low-density lipoprotein cholesterol by 10.9% (P<.01); awareness of hypertension increased by 87% (P<.0001); 20% of hypercholesterolemic patients (P<.01) and 28% of diabetic patients (P<.001) were identified; and 40% of hypertensive patients (P<.0001) were treated. Overall 4-y mortality was 12.5% in study subjects, 36.6% in renitent subjects (P<.0001 vs enrolled), and 19.9% during the period preceding the study (P<.0001 vs enrolled); cardiovascular mortality rates were 5.8%, 18.6% (P<.0001), and 11.4% (P<.0001), respectively. In particular, the frequency of fatal stroke was 0.06%, 3.8% (P<.0001), and 2.5% (P<.0001), respectively, and that of fatal coronary events was 3.4%, 7.5% (P<.0001), and 4.6% (P<.0001), respectively. In conclusion, when an epidemiologic professional staff member approaches patients in a manner similar to that of the "good father of a family," a better risk pattern and lower mortality rates (particularly cerebrovascular and coronary) are seen in those who are receptive to the care provided; those who decide not to participate in health care opportunities do not benefit. [ABSTRACT FROM AUTHOR]

In the European Project on Genes in Hypertension (EPOGH), we investigated in three populations to what extent in a family-based study, left ventricular mass (LVM) was associated with the C-532T and G-6A polymorphisms in the angiotensinogen (AGT) gene. We randomly recruited 221 nuclear families (384 parents and 440 offspring) in Cracow (Poland), Novosibirsk (Russia), and Mirano (Italy). Echocardiographic LVM was indexed to body surface area, adjusted for covariables, and subjected to multivariate analyses, using generalized estimating equations and quantitative transmission disequilibrium tests in a population-based and family-based approach, respectively. We found significant differences between the two Slavic centres and Mirano in left ventricular mass index (LVMI) (94.9 vs 80.4?g/m2), sodium excretion (229 vs 186?mmol/day), and the prevalence of the AGT-6A (55.7 vs 40.6%) and-532T (16.8 vs 9.4%) alleles. In population-based as well as in family-based analyses, we observed positive associations of LVMI and mean wall thickness (MWT) with the-532T allele in Slavic, but not in Italian male offspring. Furthermore, in Slavic male offspring, LVMI and MWT were significantly higher in carriers of the-532T/-6A haplotype than in those with the-532C/-6G or-532C/-6A allele combinations. In women, LVMI was neither associated with single AGT gene variants nor with the haplotypes (0.192/100?mmol; P=0.003), whereas such association was not present in-532T/-6A haplotype carriers (P-value for interaction 0.04). We found a positive association between LVMI and the AGT-532T allele due to increased MWT. This relation was observed in Slavic male offspring. It was therefore dependent on gender, age and ecogenetic context, and in addition it appeared to be modulated by the trophic effects of salt intake on LVM.Journal of Human Hypertension (2005) 19, 155-163. doi:10.1038/sj.jhh.1001793 Published online 14 October 2004 [ABSTRACT FROM AUTHOR]

Manidipine and lercanidipine are considered effective and safe in the treatment of chronic arterial hypertension and are equipotent in reducing blood pressure (BP) levels. Their main side effect is ankle-foot edema. After a 2-week placebo run-in period, these 2 drugs were compared in a controlled parallel-group study lasting 3 months, involving 53 patients with mild-to-moderate essential hypertension (26 assigned to manidipine and 27 to lercanidipine). At the end of the active treatment period, BP was significantly reduced in comparison with the end of the placebo phase in both the manidipine and the lercanidipine groups, without significant differences between the 2 drugs. Daytime BP was significantly reduced by 5.5%/5.6% with manidipine and by 3.8%/6.6% with lercanidipine, while smaller reductions were seen at nighttime. The smoothness index was the same with both drugs. Unlike lercanidipine, manidipine significantly reduced both basal (-30%) and minimal vascular resistance (-39%), qualifying it as a potent vasodilator. Despite vasodilation, heart rate was not increased but was even slightly reduced by treatment. Ankle-foot edema was observed with both drugs but was less pronounced with manidipine, probably because of greater postcapillary dilatation. In conclusion, manidipine and lercanidipine are both effective and safe in mild-to-moderate essential hypertension, although the former seems to have a more favorable tolerability profile than the latter. [ABSTRACT FROM AUTHOR]

An increased pulse pressure suggests aortic stiffening. New evidence also suggests that pulse pressure is a more sensitive measure of risk than other indexes of blood pressure in middle-aged and older persons. The objective of the study was to relate pulse pressure to the risk of cardiovascular events in the general population, and to assess whether pulse pressure could improve the Framingham risk prediction. A total of 378 men and 391 women over the age of 50 years (mean 62.7 years) were followed. Sex-specific Framingham cardiovascular risk scores were derived from age, systolic pressure, diastolic pressure, total and HDL cholesterol, smoking status and the presence or absence of diabetes mellitus. The cutoff points used to develop a pulse pressure score were calculated by determining the percentile points corresponding to the blood pressure categories in the Framingham risk score. We calculated relative hazard rates by multiple Cox regression. After a median follow-up of 7.2 years (range: 11 months-15 years), a total of 148 cardiovascular events occurred. In Cox regression analysis, a 10?mmHg higher pulse pressure was associated with 31% (P<0.0001) increase in the risk for cardiovascular events (fatal and nonfatal) after adjustment for sex, age, total and HDL cholesterol, smoking and the presence of diabetes mellitus. After adjustment for the aforementioned risk factors, a one-point increment in the blood pressure and pulse pressure scores was associated with a 40 and 48% (both P<0.0001) increase in the risk of fatal and nonfatal cardiovascular events, respectively. When both the blood pressure and pulse pressure scores were forced into a Cox model, only the pulse pressure score remained statistically significant (P<0.0001) with a relative hazard rate of 1.37 (CI: 1.16-1.69). These prospective data suggest that pulse pressure may improve the Framingham risk prediction among middle-aged and older individuals. Further studies, especially in the Framingham cohort, are warranted.Journal of Human Hypertension (2004) 18, 279-286. doi:10.1038/sj.jhh.1001669 [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate whether pulse pressure (PP) in elderly people is a better predictor of coronary mortality than systolic and diastolic blood pressure taken alone. For this aim, 3282 elderly subjects aged ≥65 years were studied in a population-based frame. Blood pressure was repeatedly measured and averaged; historical data, anthropometrics, blood tests and 14-year coronary mortality were recorded. Statistics included analysis of covariance, Cox analysis and bivariate vectorial analysis. Coronary mortality in women was predicted by PP (1.01 excess risk/mm Hg PP) and was significantly higher in the 3rd than in the 1st tertile of PP (relative risk 2.90); neither systolic nor diastolic pressure taken alone influenced mortality. When systolic and diastolic pressures were both entered into a Cox model, the former had a positive and the latter a negative effect on survival, confirming a prognostic role of PP. For any given level of systolic pressure, mortality was inversely associated with diastolic pressure. Finally, the mean vector representing both systolic and diastolic pressures of non-surviving women was characterised by higher systolic and lower diastolic components than in non-surviving. No significant trend of mortality in relation to either systolic blood pressure or PP was observed in men. In conclusion, the combination of systolic and diastolic pressure called PP is an independent predictor of coronary mortality in elderly females, and a better predictor than systolic or diastolic pressure alone. [ABSTRACT FROM AUTHOR]

Identifies the prognostic impact of hypertension and other cardiovascular risk factors in the elderly. Use of Mantel-Hanszel approach and multivariate Cox model for statistics; Cardiovascular mortality; Incidence of stroke and coronary artery disease; Pulse blood pressure and neck murmurs.

Stroke occurs particularly frequently in elderly people and, being more often disabling than fatal, entails a high social burden. The predictors of stroke mortality have been identified in 3282 subjects aged ≥65 years, taking part in the CArdiovascular STudy in the ELderly (CASTEL), a population-based study performed in Northeast Italy. Historical and clinical data, blood tests and 14-year fatal events were recorded. Continuous items were divided into quintiles and, for each quintile, adjusted relative risk (RR) with 95% confidence intervals [CI] was derived from multivariate Cox analysis. Age, historical stroke (RR: 5.2; 95% CI: 3.18–8.6) and coronary artery disease (RR: 1.38; CI: 1.18–2.1), atrial fibrillation (RR: 2.40; CI: 1.42–4.0), arterial hypertension (RR: 1.33; CI: 1.15–1.76), systolic blood pressure ≥ 163 mmHg (RR: 1.84; CI: 1.20–2.59), pulse pressure ≥74 mmHg (RR: 1.50; CI: 1.13–2.40), cigarette smoking (RR: 1.60; CI: 1.03–2.47), electrocardiographic left ventricular hypertrophy (RR: 1.72; CI: 1.10–2.61), impaired glucose tolerance (IGT, RR: 1.83; CI: 1.10–3.0), uric acid (UA) >0.38 mmol/l (RR: 1.61; CI: 1.14–2.10), serum potassium ≥5 mEq/l (RR: 1.70; CI: 1.24–2.50) and serum sodium ≤139 mEql/l (RR: 1.34; 1.10–2.10) increased the risk of stroke. In the CASTEL, stroke was the first cardiovascular cause of death. Some independent predictors usually unrelated to stroke mortality (namely pulse pressure, pre-diabetic IGT, UA and blood electrolytes disorders) have been identified. [ABSTRACT FROM AUTHOR]

In 1978 a random sample (367 men and 568 women aged 18-65 years) taken from the general population of a north-eastern Italian town was screened for cardiovascular risk; 16 years later, the women were invited to a second screening. Three groups were identified at the initial screening (fertile, naturally menopausal and surgically menopausal) and four in the longitudinal study (137 remained fertile during the whole study, 205 became naturally menopausal, 56 were ovariectomised and 127 were already going through the menopause). The protocol included a questionnaire, blood pressure (BP) measurement, and blood exams. Continuous variables were adjusted for confounders. Systolic BP, prevalence of hypertension, cholesterol, glycaemia and uricaemia were similar, whereas diastolic and triglycerides (TG) were lower in surgically-menopausal than in fertile women (P < 0.001). No significant difference in 16 years' variation from baseline was observed between the four groups, although women who remained fertile showed the smallest increases. In particular, neither systolic or diastolic BP increases differed between the women who were oophorectimised and those who remained fertile. 'Fertile status' was rejected from the logistic equation of incidence of hypertension, and 'age of menopause' was also rejected when this analysis was repeated in ovariectomised women. New coronary artery disease (angina pectoris or myocardial infarction) was observed in one ovariectomised woman, in three naturally menopausal, and in 13 already menopausal women which seemed to reflect the age trend. No new cases were observed in women who remained fertile. In conclusion, in Italian women surgical menopause, similarly to natural menopause, is devoid of any negative prognostic effect. [ABSTRACT FROM AUTHOR]

Although non-insulin-dependent diabetes mellitus (NIDDM) is considered a major cause of death, the role of some independent risk factors in diabetic patients is under debate. In fact the prognosis of NIDDM diabetes varies considerably in relation to the individual risk pattern, and the different studies are not directly comparable because of differences in size, age and geography of the samples, and type of statistical analysis. The aim of the study is to identify the independent predictors of mortality in a cohort of subjects with NIDDM, and to verify whether the relative risk (RR) of cardiovascular mortality is different in comparison to that of coeval non-diabetic subjects from a general population. The study includes 683 patients with NIDDM from the Northern Italian town of Pordenone, followed up for 6 years and age- and sex-matched to 683 non-diabetic subjects from a Northern Italian general population. When the two cohorts were compared, NIDDM turned out to be a strong risk factor for cardiovascular mortality (RR: 2.67). Age, coronary artery disease (RR: 1.78), arterial hypertension (RR: 1.39), macro- (RR: 2.97) and microalbuminuria (RR: 2.01) were independent predictors of cardiovascular mortality in the diabetics. In conclusion, survival of diabetic patients is worse than that of non-diabetic coeval subjects. Only few items are able to predict cardiovascular mortality in the diabetics, namely age, hypertension, CAD, macro- and microalbuminuria. [ABSTRACT FROM AUTHOR]

Provides information on a study which evaluated whether glucose levels can be modified by acute caffeine intake, and whether this effect is insulin dependent. Theoretical background; Experimental materials and methodology; Results and discussion.

Cancer mortality was analysed in 3282 elderly subjects aged ≥ 65 years from 2 cohorts of general population having different life-style patterns. They took part in the CASTEL (CArdiovascular STudy in the ELderly), a 12-year lasting prospective Italian study. The aim of the present analysis was to identify the items able to influence cancer mortality. A biochemical profile and a questionnaire on lifestyle were collected. Continuous items were averaged and compared with analysis of variance, frequencies with the Pearson's ϰ2 test. Mortality was recorded yearly for 12 years from the Registrar's Office and causes of death double-checked by consulting medical case sheets and family doctors' files. The influence of items on mortality was evaluated with the Cox multivariate analysis. Relative risk (RR) of each item was adjusted for confounders. Age, gender, tobacco smoking, the presence of respiratory symptoms, low body mass index in males, serum alanine transaminase (ALT) and alkaline phosphatase (ALP), as well as the town of residence, were powerful predictors of cancer mortality. In the entire population, 12-year overall mortality was 49.4%, cardiovascular 22.8%, and neoplastic 11%; the latter was higher in males than in females (15.7% vs. 7.9%, p < 0.00001). In subjects with respiratory symptoms neoplastic mortality was 11.6% (RR: 1.47) vs. 9.7% in those without symptoms (p < 0.01). Subjects with very low cholesterol (≤ 178 mg/dl), those with high uric acid (≥ 8.7 mg/dl) and males with low body mass index (≤ 22.7 kg/m2) has an increased risk of cancer mortality. RR of cancer mortality increased with increasing ALT or ALP. It was ∼1 in those having ALT and ALP between 9 and 41.2U/I, 1.41 in those exceeding this latter level and < 1 in those below 9U/I. RR of ALP had a similar trend, the best protective cut-off value being <106 and the worst one > 177U/I. When both serum enzymes were simultaneously raised, RR of cancer mortality increased to 2.84. [ABSTRACT FROM AUTHOR]