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Hypnotic-focused analgesia (HFA) was produced in 20 highly hypnotizable subjects receiving nociceptive stimulations while undergoing functional magnetic resonance imaging (fMRI). The fMRI pattern in brain cortex activation while receiving a painful stimulus was recorded both during nonhypnosis and during HFA. The scanning protocol included the acquisition of a T1-weighted structural scan, 4 functional scans, a T2-weighted axial scan, and a fluid attenuated inversion recovery (FLAIR) scan. Total imaging time, including localization and structural image acquisitions, was approximately 60 minutes. Without HFA, the subjects reported subjective presence of pain, and the cortex primary sensory areas S1, S2, and S3 were activated. During HFA, the subjects reported complete absence of subjective pain and S1, S2, and S3 were deactivated. The findings suggest that HFA may prevent painful stimuli from reaching the sensory brain cortex, possibly through a gate-control mechanism. [ABSTRACT FROM AUTHOR]

Objectives: To determine if postmenopausal women have different arterial stiffness, blood pressure (BP) values, or metabolic patterns in comparison to fertile women and to men at a population level. Methods: This is a population-based epidemiologic study of 1853 representative men and women aged 18-95 years. Clinostatic humeral BP was measured using Omron 705CP. Aortic BP, augmentation index (AI), and pulse wave velocity (PWV) were determined using applanation tonometry. Body mass index (BMI) and subscapular skinfold thickness were used as measures of adiposity. Fasting and postload blood glucose, homeostasis model assessment (HOMA), low-density and high-density lipoprotein serum cholesterol (LDL-C and HDL-C) and triglycerides were assessed. Results: Age was higher in postmenopausal women than in fertile women (68.8±9.5 vs. 35.7±10.2 years, p<0.001), and BMI was 16% higher ( p<0.01) in the postmenopausal women after age adjustment. Humeral and aortic BP, carotid and radial AI, carotid-femoral PWV, BMI, LDL-C, LDL-C/HDL ratio, triglycerides, glucose tolerance, HOMA, and skinfold thickness were apparently higher in postmenopausal than in fertile women. Using multivariate analysis, however, all these differences were abolished after adjusting for confounders (age and, when appropriate, BMI), except for LDL-C, which remained 19% higher ( p<0.01) in postmenopausal women than in fertile women after adjusting for many confounders (age, BMI, cholesterol, ethanol intake, caloric intake, and triiodothyronine). Conclusions: Only LDL-C increases in postmenopausal women, whereas other differences attributed to menopause, including BP and arterial stiffness, seem to be confounding effects of age and BMI. [ABSTRACT FROM AUTHOR]

The efficacy of hypnotic suggestion of high performance was evaluated in 10 young healthy volunteers undergoing isometric exercise (hand grip) in basal conditions of usual normal consciousness and in profound hypnosis. To this aim, they were asked to perform dynamometric hand grip at maximal muscular strength and for the longest time compatible with individual tolerance. As a specific suggestion, a hallucination of drinking an 'energizing potion' capable of increasing muscular performance and abolishing the sense of fatigue and pain associated with isometric exercise was induced. Haemodynamic parameters were continuously measured. In comparison to basal conditions of usual consciousness, the exercise performer under hypnotic suggestion was associated with a 12% increase in maximal muscular strength and a 60% increase in exercise length. A greater increase of heart rate, arterial blood pressure, and double product-accompanied by a lower increase of stroke voLume and consequently of cardiac index-was recorded. Nevertheless, exercise-induced vasodilation was comparable in the two conditions, so that the increase in cardiac index observed during hypnotic suggestion was entirely sustained by heart rate increase. Such a condition can only be tolerated for a short time and at the expense of a reduced myocardial (particularly subendocardic) perfusion. It seems therefore that the hypnotic command 'perform over your natural limits' is followed by an increase in strength but particularly in exercise length. In such conditions, physical performance is actually greater than that achieved in normal conditions, as if the subject was able to draw on energies not usually employed in everyday life. This higher performance is unnatural and is sustained by muscular mechanisms activating unfavourable, and potentially dangerous, haemodynamic reflexes. Although hypnosis is a formidable tool in the study of human physiology, its use in the physical world (particularly sporting activities) should be limited to specific controlled con- ditions. In fact, by increasing muscular power and decreasing the sense of fatigue, hypnosis seems to be able to deprive subjects of the natural feedback mechanisms well-synthesized in the sentences 'It's too much for me' or 'I can't take it any more'. [ABSTRACT FROM AUTHOR]

Background: Both low and high iron levels have been associated with cardiovascular outcome. The aim of this study was to determine if dietary iron intake is a cardiovascular predictor in women at a population level. Methods: A 138-item food frequency questionnaire (FFQ) was administered to 906 women aged 61.1±17.1 years from an unselected general population followed for 10 years. The mass of dietary items was calculated, and each food was resolved into its chemical components according to food composition tables conceived for Italian food. Results: An inverse association between iron intake and cardiovascular morbidity was found. Incident nonfatal cerebrovascular events were 10 of 302 (3.3%), 4 of 302 (1.3%), and 2 of 302 (0.7%) in the first, second, and third tertiles of nonheme iron intake ( p for trend <0.01), respectively; fatal cerebrovascular events were 20 of 302 (6.6%), 13 of 302 (4.3%), and 5 of 302 (1.7%), respectively ( p<0.01); nonfatal coronary events were 24 of 302 (7.9%), 13 of 302 (4.3%), and 10 of 302 (3.3%), respectively, and fatal coronary events were 20 of 302 (6.6%), 15 of 302 (5.0%), and 10 of 302 (3.3%), respectively ( p<0.01). Independenly of confounders, hazard ratios (HR) and 95% confidence intervals (CI) of being the first rather than third tertile of nonheme iron intake were 5.00 (1.08-23.26), 3.18 (1.41-10.12), and 3.25 (1.39-7.59), respectively, for cerebrovascular and 2.48 (1.17-5.25), 2.25 (1.03-4.80), and 2.51 (1.39-4.53), respectively, for coronary events. Heme iron intake was not a predictor. Conclusions: Based on a longitudinal population analysis, low iron intake seems to be an independent predictor of cerebrovascular and coronary morbidity and mortality in women. [ABSTRACT FROM AUTHOR]

To verify whether the C825T polymorphism of the GNB3 influences the response to neuropsychological tests, mini-mental state examination, digit span (DS), immediate and delayed prose memory, memory with interference at 10 and 30 seconds (MI 10 and 30), trail making tests (TMTs) A and B, abstraction task, verbal fluency (VF) test, figure drawing and copying, overlapping figures test and clock testwere performed in 220 elderlymen andwomen free fromclinical dementia and fromneurological and psychiatric diseases randomly taken from the Italian general population and analysed across the C825T polymorphism.The performance of DS, immediate and delayed prosememory, VF, and TMTs was worse in subjects who were TT for the polymorphism in comparison to the C-carriers.The performance of all tests declined with age. In the case of DS, immediate and delayed prose memory, MI 10 and VF, this trend wasmaintained in the C-carriers but not in TT. In the case of prosememory, ofmemory with interference, and of VF, schooling reduced the detrimental interaction between age and genotype. The C825T polymorphism of GNB3 gene therefore influences memory and verbal fluency, being additive to the effects of age and partially mitigated by schooling. [ABSTRACT FROM AUTHOR]

Background: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort., Methods and Results: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P <0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P =0.004) and 1.150 (95% CI, 1.021-1.295, P =0.02), respectively., Conclusions: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

Objective: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension., Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders., Results: A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole database: SUA more than 5.34 mg/dl (confidence interval 4.37-5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78-5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284-2.109, P < 0.0001) for all heart failure and 1.645 (1.284-2.109, P < 0.0001) for fatal heart failure, respectively., Conclusion: The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).

Objective: The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men., Methods: The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months., Results: A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P < 0.01), but not in men., Conclusion: The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.

Background The general belief is that caffeine increases the risk of hyperkinetic arrhythmias, including atrial fibrillation. The aim of this study is to investigate the effect of chronic caffeine intake on incident atrial fibrillation in general population. Design and methods A population cohort of 1475 unselected men and women observed for 12 years and left free to intake food or beverages containing caffeine was studied. Subjects were stratified into tertiles of caffeine intake both in the whole cohort and after genotyping for the -163C > A polymorphism of the CYP1A2 gene, regulating caffeine metabolism. Results In the whole cohort, the 12-year incidence of atrial fibrillation was significantly lower in the third (2.2%) than in the first (10.2%) or second (5.7%) tertile of caffeine intake ( P < 0.001). The same trend was observed in all genotypes; the apparently steeper reduction of atrial fibrillation in slow caffeine metabolisers found at univariate analysis was proved wrong by multivariate Cox analysis. Age, chronic pulmonary disease, history of heart failure and of coronary artery disease, and systolic blood pressure - but not the genotype or the caffeine ×  CYP1A2 interaction term - were significant confounders of the association between incident atrial fibrillation and being in the third tertile of caffeine intake (hazard ratio 0.249, 95% confidence intervals 0.161-0.458, P < 0.01). Conclusions A higher caffeine intake (>165 mmol/day or > 320 mg/day) is associated with a lower incidence of atrial fibrillation in the 12-year epidemiological prospective setting based on the general population.

Background and Aims: The possible effect of caffeine as an enhancer of cognitive performance, particularly that on abstract reasoning, has never been studied in an epidemiological setting, especially in relation to -163C>A polymorphism of CYP1A2 gene, largely controlling caffeine metabolism. Aim of this study was to ascertain whether in general population free chronic caffeine intake modifies abstract reasoning, and if this effect is influenced by the above mentioned genotype, by age, schooling, ethanol intake and smoking habits., Methods: We studied 1374 unselected men and women aged 51 ± 15 years (range 18-89) from a general population. Daily caffeine intake deriving from coffee, tea, chocolate or cola was calculated from an anamnestic questionnaire and from a 7-day dietary diary. Abstract reasoning was measured in the frame of a neuropsychological assessment as the ability to find a concept linking two words indicating objects or actions and explaining how they were connected., Results: In age-schooling-adjusted linear regression, the higher the caffeine intake, the better the abstraction score. Abstract reasoning depended on caffeine in the -163C>A CC homozygous only (so-called slow metabolizers), where it was higher in the 3rd tertile of caffeine intake. Age and ethanol reduced while smoking and schooling enhanced this association. The interaction term between caffeine and the -163C>A polymorphism was accepted in linear regressions. Caffeine consumption resulted innocuous for the A-carriers (so-called fast metabolizers)., Conclusions: In general population, a positive association between caffeine intake and abstract reasoning exists in the CC homozygous of the -163C>A polymorphism of CYP1A2 gene., (Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Objective: The enzyme xanthine oxidoreductase (XOR) generates uric acid in the terminal steps of the purine metabolism; meanwhile reactive oxygen species are formed. We hypothesized that uric acid production, as assessed indirectly from XOR variants, is associated with hypertension., Methods: Among 2769 participants (48.3% men; mean age 40.7 years) randomly recruited from European populations, we genotyped 25 tagging XOR SNPs and measured blood pressure (BP) at baseline and follow-up (median 8.8 years). The relation between variants of the XOR gene with changes in pulse pressure and mean arterial pressure over time; and incidence of hypertension, were analyzed., Results: Compared with nonminor allele carriers, pulse pressure increased approximately 2 mmHg more in minor allele carriers of rs11904439 (P = 0.01), whereas mean arterial pressure and DBP increased approximately 1 mmHg less in minor allele carriers of rs2043013 (P = 0.01). In 2050, participants normotensive at baseline, hazard ratios contrasting risk of hypertension in minor allele carriers vs. nonminor allele carriers were 1.31 (95% confidence interval 1.03-1.68; P = 0.02) and 1.69 (95% confidence interval 1.11-2.57; P = 0.01) for rs11904439 and rs148756340, respectively. With the false discovery rate set at 0.25, the aforementioned associations retained significance. The changes in SBP from baseline to follow-up and the serum levels of uric acid at baseline (n = 1949) were not associated with XOR., Conclusion: Pending confirmation, our findings suggest that variation in uric acid production, as captured by genetic variation in XOR, might be a predictor of changes in BP and in the risk of hypertension.

Background: The general belief that orthostatic hypotension (OH) predisposes to cardiovascular events is based on sparse and contradictory data, rarely derived from population studies., Methods: A total of 1,016 men and women aged ≥65 years was studied in a 12-year epidemiological population-based study. Cardiovascular events were detected in subjects with and without OH (blood pressure (BP) decrease ≥20mm Hg for systolic or ≥10mm Hg for diastolic), and Cox analysis was performed including OH as an independent variable., Results: In univariate analysis, coronary (20.2% vs. 13.1%, P = 0.05), cerebrovascular (13.1% vs. 8.4%, P = 0.05), and heart failure (HF) events (20.2% vs. 13.8%, P = 0.03) were apparently more incidental in subjects with OH than in those without OH. Nevertheless, after adjusting for age, gender, and systolic BP as confounders, OH did not act as a cardiovascular predictor (relative risk for cerebrovascular events 1.33, 95% confidence interval (CI), 0.78-2.2, for coronary events 1.25, CI 0.82-1.88, for HF 1.07, CI 0.71-1.62, for arrhythmias 0.82, CI 0.40-1.37, and for syncope 0.58, CI 0.13-2.71)., Conclusions: Although OH seems to be a predictor of coronary, cerebrovascular, and HF events, no predictive role was found in models that include biological confounders. Independent of the cause of OH, age and systolic BP, which are positively associated with OH, fully explain the greater incidence of cardiovascular events and the greater cardiovascular risk observed in subjects with OH.

Background: The role of C825T polymorphism of the candidate GNB3 gene in predicting cerebrovascular outcome has been poorly explored in longitudinal setting at a population level., Methods: In an epidemiological setting, 1,678 men and women from general population were genotyped for C825T polymorphism of GNB3 gene and follow-up for 10 years to detect nonfatal and fatal cerebrovascular events (CE). Established cerebrovascular risk factors were used to adjust the multivariate Cox analysis for confounders., Results: Seventy-three nonfatal and 30 fatal CE were recorded. Incidence of CE was higher in TT than in C-carriers (fatal: 2.6 vs. 1.7%, P < 0.03; nonfatal: 7.8 vs. 3.9%, P < 0.03; fatal recurrences: 1.6 vs. 0.6%, P < 0.03). In Cox analysis, the TT genotype predicted nonfatal (hazard ratio 1.99, 95% confidence interval 1.05-3.79, P = 0.03), fatal (2.91, 1.05-8.12, P = 0.04), and fatal recurrent CE (6.82, 1.50-31.1, P = 0.02) also after adjustment for age, gender, systolic and diastolic blood pressure, body adiposity, atherogenetic blood lipids, serum uric acid, diabetes, calories, caffeine and ethanol intake, and coronary events at baseline. Further adjustment for historical CE made the association between TT genotype and incident fatal CE nonsignificant (hazard ratio 2.72, 95% confidence interval 0.96-7.22, P = 0.06)., Conclusions: The TT genotype of GNB3 gene predicts incident CE independent of blood pressure and other established risk factors at a population level. Further studies are needed to clarify the nature and pathways of this association.

Objective: Menopause is considered to be a cardiovascular risk factor, but this belief is based on opinions rather than on evidence. Confounding effects of age are often neglected., Design: Population-based study with further subanalysis of case-to-case age-matched cohorts of men and fertile and menopausal women., Setting: Epidemiology in primary, public, institutional frame., Participants: Nine thousand three hundred and sixty-four men and women aged 18-70 years representative of Italian general population followed-up for 18.8 +/- 7.7 years., Main Outcome Measures: Blood pressure (BP), prevalence and incidence of hypertension, serum total, high-density lipoprotein and low-density lipoprotein cholesterol, glucose tolerance, body adiposity, vascular reactivity, target organ damage, overall and cardiovascular mortality and morbidity, by gender and by menopausal status., Results: Cross-sectional: crude BP, pressor response to cold, orthostatic BP decrease, BMI, skinfold thickness, fasting and postload blood glucose and insulin, serum lipids, left ventricular mass, serum creatinine, microalbuminuria and augmetantion index were higher in menopausal than in fertile women, and comparable in menopausal women and men, a difference that was no longer present when adjusting for age or considering age-matched cohorts. Longitudinal: BP increase during follow-up, cardiovascular mortality and morbidity were greater in menopausal than in fertile women, and comparable in menopausal women and men, a difference no longer present in age-matched cohorts. Menopausal status was rejected from multivariate Cox analysis also including age., Conclusion: The cardiovascular effects usually attributed to menopause seem to be a mere consequence of the older age of menopausal women.

Background: The role of body mass index (BMI) as a factor influencing longevity of the elderly subject is still under debate., Objective: To evaluate at a population level whether or not BMI is a risk factor of mortality in the elderly, highlighting possible gender-related differences., Methods: 3,282 Subjects aged 65-95 years, were recruited from an Italian general population and 12-year events were recorded. Blood tests and anthropometric measurements were performed. BMI as a continuous item was divided into quintiles and, for each quintile, adjusted hazard ratio (HR) with 95% confidence intervals for mortality was derived by classes of age and gender from Cox analysis., Results: BMI inversely predicted overall and cancer mortality in men only. Overall mortality rate was 64.7% (HR = 1.63 [1.23-2.71]) in the 1st quintile of BMI, 54.9% (1.21 [0.92-1.73]) in the 2nd, 54.1% (1.20 [0.85-1.67]) in the 3rd, 53.3% (1.04 [0.82-1.32]) in the 4th and 52.5% in the 5th; cancer mortality rate was 23.1% (HR = 2.35 [1.31-4.23]), 14.2% (HR = 1.19 [0.65-1.80]), 15.8% (HR = 1.49 [0.93-2.39]), 15.8% (HR = 1.36 [0.84-2.16]) and 13.4%, respectively. The relationship between BMI and mortality remained significant only in men aged 76 years or less. No relationship was found between BMI and coronary or cerebrovascular mortality., Conclusions: BMI <22.7 kg/m2 does not improve survival in the elderly, while it is an independent predictor of cancer mortality in men aged

Objectives: To investigate the role of low-density lipoprotein cholesterol (LDL-C) as a predictor of mortality in elderly subjects., Design: Population-based prospective cohort study., Setting: Two communities in northern Italy., Participants: Three thousand one hundred twenty Caucasian subjects aged 65 and older recruited in for the Cardiovascular Study in the Elderly and followed up for 12 years., Measurements: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL-C, glucose, creatinine, and body mass index. Clinical measures: medical assessment, diabetes mellitus, hypertension, stroke, coronary disease, heart failure, and smoking and drinking habits. Vital status measures: death certificates from the Registry Office and causes of death according to the International Classification of Diseases. After plotting mortality rates using quartiles of LDL-C, relative hazard rates (RHRs) were calculated using multivariate Cox regression analyses. When the trend was nonlinear, the RHRs were further calculated for the 25th, 50th, and 75th percentiles of the distribution to confirm curvilinearity., Results: The distribution of risk of total mortality in women and of fatal heart failure in all subjects was curvilinear (non J-shaped), decreasing nonlinearly with LDL-C. For total mortality in men and cardiovascular mortality in both sexes, the relationship with LDL-C was J-shaped. The risk of fatal myocardial infarction was J-shaped in men, whereas it increased linearly with higher LDL-C in women. In both sexes, the association between stroke mortality and LDL-C was not significant., Conclusion: This study adds to the uncertainty of the role of elevated levels of LDL-C as a risk factor for mortality in old people.

Congestive heart failure (CHF) is highly prevalent in the elderly. The aim of this study was to identify the predictors of CHF mortality in patients over 65 years of age who were free of CHF at initial screening. A total of 3,282 elderly subjects were recruited in a population-based frame and 12-year events were recorded. Continuous items were divided into tertiles and for each tertile adjusted the relative risk (RR) with 95% confidence intervals (CI) was derived in both genders from multivariate Cox analysis of CHF mortality. Age > or = 72 years ([RR]: 2.24; 95% CI 1.56 - 3.24), male gender ([RR]: 1.4; 95%CI 1.02 - 1.76), clinical history of coronary artery disease ([RR]: 1.25; 95% CI 1.02 - 1.76), pulse pressure > or = 79 mmHg ([RR]: 1.33; 95% CI 1.03 - 1.87), heart rate > or = 81 bpm ([RR]: 1.32; 95% CI 1.10 - 1.96), atrial fibrillation ([RR]: 1.82; 95% CI 1.18 - 2.81), left ventricular hypertrophy ([RR]: 1.42; 95% CI 1.01 - 2.02), diabetes ([RR]: 1.35; 95% CI 1.02 - 1.78), vital capacity < or = 81% of the theoretical value ([RR]: 2.50; 95% CI 1.88 - 3.32), forced expiratory volume in 1 second < or = 72% of the theoretical value ([RR]: 2.02; 95% CI 1.55 - 2.72) and serum sodium level < or = 139 mmol/L ([RR]: 1.95; 95% CI 1.44 - 2.63) predicted CHF mortality. This model is able to identify elderly people at increased risk of death from CHF.

Mortality and morbidity appear to be higher in a Cimbrian population representing an enclave of people who migrated from medieval Germany to the secluded Leogra valley in Italy. A population-based study was organized, recruiting 881 elderly subjects of Cimbrian origin and comparing them with a standard control population (SCP, n = 3,282) having comparable general characteristics and lifestyle. Serum lipids and glucose, blood pressure, heart rate, respiratory function, ECG abnormalities, and historical events were used as risk indicators. Age-adjusted systolic and pulse pressure were higher in the Cimbrians than in the SCP, while diastolic blood pressure was comparable. The prevalences of arterial hypertension, isolated systolic hypertension, and pulse hypertension were significantly more represented among Cimbrians than SCP. The prevalences of diabetes, hypercholesterolemia, and hypertriglyceridemia were higher among the former than the latter. The ratio between apolipoproteins B and A1 was also higher, while the HDL fraction was significantly lower in Cimbrians than in the SCP. In Cimbrians, the relative risk (RR) for ischemic heart disease was 1.92 (1.57-2.34) in women, 2.30 (1.54-3.43) in men and 1.03 (1.00-1.06) in women for stroke, 2.43 (1.54-3.83) in men and 1.45 (1.01-1.12) in women for atrial fibrillation, 3.85 (2.83-5.24) in men and 1.39 (1.20-1.60) in women for respiratory disease, 1.97 (1.32-2.94) in men and 6.81 (4.38-10.60) in women for intermittent claudication, and 3.31 (2.44-4.50) in men and 2.30 (1.76-3.01) in women for left ventricular hypertrophy. The subjects living in the secluded Leogra valley are at higher cardiovascular risk than the standard controls. Whether this depends on genetic factors, lifestyle, or both will need to be clarified by further analysis.

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.

Methods: The association of blood pressure (BP) with the beta-adducin C1797 T polymorphism was investigated in 388 men and 456 women aged 18-60 years recruited from three European populations (Cracow, Poland, n=300; Novosibirsk, Russian Federation, n=274; Mirano, Italy; n=270). Phenotypes included conventional measurements of BP obtained at the second contact with the subjects and 24-h ambulatory BP. Subjects were genotyped for the beta-adducin C1797 T polymorphism. Both a population-based association study and a family-based analysis were performed., Results: Urinary sodium excretion was higher in Cracow than in Mirano (241 versus 185 mmol/day, P<0.05) and intermediate in Novosibirsk (206 mmol/day). The beta-adducin T allele (15.2 versus 9.1%, P<0.0001) was more prevalent in Mirano than in the two Slavic centres. In both population-based and family-based association analyses, there was significant heterogeneity between Slavic and Italian subjects in the phenotype-genotype relationships with beta-adducin. Adjusted population-based analyses demonstrated that in the two Slavic centres, values of systolic pressure obtained by 24-h, daytime and night-time ambulatory monitoring, but not those measured by conventional sphygmomanometry at home, were significantly higher in T allele carriers than in CC homozygotes. These results were confirmed in the family-based analysis of offspring using a quantitative transmission disequilibrium test., Conclusions: Phenotype-genotype associations involving blood pressure are influenced by the technique and conditions of the BP measurement as well as by the overall ecogenetic context.

Background: The aim of this study was to evaluate at a population level whether hypertension is a risk factor for cardiovascular mortality and to verify whether or not this is true for both genders at any age., Methods: This population-based, long-lasting, prospective study includes a 14-year mortality (institutional epidemiology in primary care). Unselected, unbiased subjects (5185) aged 22 to 95 years were recruited from the Italian general population, and divided into normotensive (<140 mm Hg systolic blood pressure [BP] and <90 mm Hg diastolic BP and untreated) and hypertensive groups. The main aim was to identify the significant predictors of mortality due to stroke, coronary artery disease, heart failure, and pulmonary embolism, and to quantify the age-adjusted relative risk of hypertension in men and women, at different age classes (<70, 70 to 79, >or =80 years) for each mortality cause. The analysis was repeated among 1091 normotensive and 1091 hypertensive age-matched subjects to clean statistics from the effects of age., Results: There were 846 cardiovascular deaths, 178 due to stroke, 273 to coronary disease, 351 to heart failure, and 44 to pulmonary embolism. Hypertension predicted stroke mortality, but not that due to other causes. This prediction was only significant in women, not in men. No prediction was possible after the age of 80 years. Age-matching increased the significance level of stroke mortality prediction in women aged <80 years; in these women, systolic BP predicted stroke mortality directly and diastolic inversely. CONCLUSIONS; In this population, hypertension predicted only stroke mortality in women aged <80 years. High systolic and low diastolic BP were predictive of stroke mortality, confirming a prognostic role for high pulse pressure.

The question on whether menopause is an independent cardiovascular risk factor is still under debate. The results of four studies conducted by our staff in North East Italy, including > 11,000 subjects from the general population and covering a range of ages from 18 to 95 years, have been employed. We found apparently higher blood pressure (BP) values in naturally menopausal than in fertile women, but this difference disappeared after age-correction, or after identifying fertile and menopausal age-matched women. Significantly higher levels of serum lipids were also observed in menopausal than in fertile women but, in this case too, any difference disappeared after age-correction/matching. In a 16-year longitudinal analysis we found that BP increase and incidence of hypertension were the same in the women who remained fertile, in those becoming naturally menopausal and in those already menopausal at baseline; going through the menopause period, therefore, has no effect on BP. A mild and transitory BP increase was only observed during the climacterium. The BP increase during a follow-up and the incidence of new cases of hypertension were also similar in the women who remained fertile and in those who underwent bilateral ovariectomy, indicating no direct effect on BP for surgical menopause. In contrast, vectorial analysis demonstrated an excess increment of serum lipids among the women who underwent oophorectomy. In our populations, menopause had no predictive role and was rejected from the multivariate equations of risk, cardiovascular risk being completely explained by age and BP (both higher in menopausal then in fertile women).