The ROVIGO study (risk of vascular complications: impact of genetics in old people): protocol, study design, and preliminary results of the initial survey : cardiovascular epidemiology in the elderly.

BACKGROUND: The epidemiology of cardiovascular risk (CV) in the elderly is far from being defined, and the reasons why some subjects retain a healthy body while growing old while others are affected by different diseases or die prematurely are still unknown. AIMS: To compare the CV risk pattern in two elderly cohorts living in North-East Italy. MATERIALS AND METHODS: The Risk Of Vascular complications: Impact of Genetics in Old people (ROVIGO) study is a population-based study including 580 unrelated elderly subjects representative of general population living in Rovigo in the Veneto region. They were compared to a cohort of 580 age-gender-matched unrelated subjects from the CArdiovascular STudy in the Elderly (CASTEL) living in the same region in Castelfranco Veneto and Chioggia. RESULTS: Blood pressure (BP), heart rate (HR), low-density-lipoprotein cholesterol, and prevalence of coronary heart disease, heart failure and chronic pulmonary disease were lower in the ROVIGO than in the CASTEL cohort, while high-density-lipoprotein cholesterol and the prevalence of diabetes were higher in the former than in the latter. In the ROVIGO cohort, diabetes, left ventricular hypertrophy, coronary and cerebrovascular diseases were more represented in men. In the CASTEL cohort, systolic BP was higher in women. In both cohorts, the lipid pattern was less favourable and HR higher in women, chronic pulmonary disease more represented in men. CONCLUSIONS: People living in Rovigo were at lower CV risk than those in Castelfranco Veneto and Chioggia, mainly due to lower BP values, better lipid pattern and lower prevalence of CV and pulmonary disease.

Cognitive functions and cognitive reserve in relation to blood pressure components in a population-based cohort aged 53 to 94 years.

In 288 men and women from general population in a cross-sectional survey, all neuropsychological tests were negatively associated with age; memory and executive function were also positively related with education. The hypertensives (HT) were less efficient than the normotensives (NT) in the test of memory with interference at 10 sec (MI-10) (-33%, P = 0.03), clock drawing test (CLOX) (-28%, P < 0.01), and mini-mental state examination (MMSE) (-6%, P = 0.02). Lower MMSE, MI-10, and CLOX were predicted by higher systolic (odds ratio, OR, 0.97, P = 0.02; OR 0.98, P < 0.005; OR 0.95, P < 0.001) and higher pulse blood pressure (BP) (OR 0.97, P = 0.02; OR 0.97, P < 0.01; and 0.95, P < 0.0001). The cognitive reserve index (CRI) was 6% lower in the HT (P = 0.03) and was predicted by higher pulse BP (OR 0.82, P < 0.001). The BP vectors of lower MMSE, MI-10, and CLOX were directed towards higher values of systolic and diastolic BP, that of low CRI towards higher systolic and lower diastolic. The label of hypertension and higher values of systolic or pulse BP are associated to worse memory and executive functions. Higher diastolic BP, although insufficient to impair cognition, strengthens this association. CRI is predicted by higher systolic BP associated to lower diastolic BP.

The C825T GNB3 polymorphism, independent of blood pressure, predicts cerebrovascular risk at a population level.

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.

Dietary iron intake and cardiovascular outcome in Italian women: 10-year follow-up.

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.

Neurophysiological correlates of post-hypnotic alexia: a controlled study with Stroop test.

To clarify whether hypnotically-induced alexia was able to reduce the Stroop effect due to color/word interference, 12 volunteers (6 with high and 6 with low hypnotizability according to Stanford Hypnotic Susceptibility Scale Form C) underwent a Stroop test consisting of measuring, both in basal conditions and during post-hypnotic alexia, the reaction times (RT) at appearance of a colored word indicating a color. In basal conditions, RT were greater in case of incongruence. In highly hypnotizable participants, the interference was less pronounced during post-hypnotic alexia (-34%, p = 0.03). During alexia, late positive complexamplitude was also greater for congruent than incongruent conditions (p < 0.03), and cardiovascular response to stress was less pronounced as well. In participants showing low hypnotizability, no reduction of Stroop effect was detected during post-hypnotic alexia. Posthypnotic alexia is therefore a real and measurable phenomenon, capable of reducing the color-word interference and the haemodynamic effects of the Stroop test.

Menopause does not affect blood pressure and risk profile, and menopausal women do not become similar to men.

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.

Electrocardiographic criteria of left ventricular hypertrophy in general population.

The question on whether the electrocardiographic criteria are reliable for detection of left ventricular hypertrophy (LVH) and play a role in predicting outcome is open. Answer can only proceed from population-based studies over unselected people followed up for years. In this study, 1,699 subjects from general population underwent echocardiogram and standard electrocardiogram (ECG) codified for LVH with Minnesota code and with other five methods. Other items were also recorded and used as covariables. Left ventricular mass index (LVMI) was 127.6 +/- 44.9 g m(-2) in men and 120.8 +/- 41.2 g m(-2 )in women, and correlated directly with age in both genders. Prevalence of echocardiographic LVH was 36.6% in men and 53.4% in women. LVMI correlated directly with the Sokolow-Lyon score in both genders at any age, with the Romhilt-Estes, Cornell and R(aVL) scores in all subjects but elderly men, and with the Lewis score in men and women aged < or =69 years. Sensitivity and the predictive value of electrocardiographic tests, as well as the prevalence of LVH diagnosed with electrocardiographic criteria, were always low. Specificity was high for all the tests, and in particular for the Cornell index. Only when diagnosed with echocardiogram or with the Sokolow-Lyon criterion, LVH was an independent predictor of mortality. We conclude that electrocardiographic tests cannot be used as a surrogate of echocardiogram in detecting LVH in the general population because their positive predictive value (PPV) is unacceptably low. On the contrary, they could replace echocardiography in the follow up and for prediction of outcome, when LVH has previously been correctly diagnosed with other methods.

Effects of the C825T polymorphism of the GNB3 gene on body adiposity and blood pressure in fertile and menopausal women: a population-based study.

OBJECTIVES: The 825T allele of the GNB3 gene is implicated in adipose distribution, predisposing to obesity and hypertension. Menopause is also considered a condition leading to excess adiposity and hypertension. The aim of the present study was to clarify whether the effects of menopause on body weight and blood pressure are influenced by the C825T polymorphism of the GNB3 gene. METHODS: The study involved 1339 subjects (43% men) aged 18-95 years, genotyped at the GNB3 825 locus, undergoing, in an epidemiological population-based frame, questionnaire, anthropometrics and blood examinations. RESULTS: Mean skinfold thickness (MST), truncal obesity and excess subcutaneous adiposity (MST greater than median) were higher in women than in men. A significant interaction was detected between menopausal status and the C825T polymorphism (Pint > 0.0001). MST, truncal obesity and excess subcutaneous adiposity were lower in CC fertile than menopausal women, but were comparable in TT fertile and menopausal women. In a multivariate logistic model for excess subcutaneous adiposity, the relative risk of menopause was 4.12 (95% confidence interval 2.35-7.22) in CC women but was insignificant in the other two genotypes. In fertile women only, higher systolic blood pressure (SBP) was detected in TT than in CC genotypes. CONCLUSION: An interaction exists between the C825T polymorphism and menopause in controlling body adiposity and blood pressure in women. Adiposity and SBP are higher in menopausal than in fertile women, provided they have the CC genotype. TT fertile women show the same adiposity as those in menopause. Men have the same excess adiposity as menopausal women, independent of the GNB3 genotype.

Skinfold thickness and blood pressure across C-344T polymorphism of CYP11B2 gene.

OBJECTIVE: To ascertain whether body adiposity is associated with the C-344T polymorphism of the CYP11B2 gene codifying for aldosterone synthase. DESIGN: A cross-sectional epidemiological evaluation of a highly homogeneous unselected general population of Caucasians. METHODS: Lifestyle, medical history, anthropometrics, subscapular, triceps and suprailiac skinfold thickness, lying blood pressure and biochemical measures were recorded in a population-based study among 1386 unselected subjects (56.5% women) living in a secluded valley. All were genotyped for C-344T allele status. Continuous variables were compared across genotypes with analysis of covariance and correlations evaluated using the Pearson method. Odds ratios (OR) were calculated for the TT and CT genotype versus the CC homozygotes and compared with the T-carriers with a logistic model. RESULTS: The C-344T genotypic frequency did not deviate from Hardy-Weinberg equilibrium. In women, higher values of triceps and subscapular skinfold thickness were found in the CC homozygotes than in the T-carriers. In this sex, skinfold thickness also directly correlated with both systolic and diastolic blood pressure in the T-carriers only. The logistic regression for the dependent variable arterial hypertension showed an influence of triceps [OR 1.07, 95% confidence interval (CI) 1.02-1.12, P=0.006], subscapular (OR 1.13, 95% CI 1.06-1.20, P<0.0001) and suprailiac (OR 1.08, 95% CI 1.01-1.15, P=0.03) skinfold in T-carrier women only. These relationships were not detectable in men. The aldosterone-to-renin ratios were comparable across genotypes and sexes. CONCLUSION: The C-344T polymorphism of the CYP11B2 gene seems to exert a sex-specific influence on body adiposity, independent of adrenal aldosterone.

Hypnosis prevents the cardiovascular response to cold pressor test.

To highlight the effects of hypnotic focused analgesia (HFA), 20 healthy participants underwent a cold pressor test (CPT) in waking basal conditions (WBC) by keeping the right hand in icy water until tolerable (pain tolerance); subjective pain was quantified by visual scale immediately before extracting the hand from water. The test was then repeated while the participants were under hypnosis and underwent HFA suggestions. Cardiovascular parameters were continuously monitored. Pain tolerance was 121.5+/-96.1 sec in WBC and 411.0+/-186.7 sec during HFA (p < 0.0001), and visual rating score 7.75+/-2.29 and 2.45+/-2.98 (p < 0.0001), respectively. CPT-induced increase of total peripheral resistance was non significant during HFA and +21% (p < 0.01) in WBC. HFA therefore reduced both perception and the reflex cardiovascular consequences of pain as well. This indicates that hypnotic analgesia implies a decrease of sensitivity and/or a block of transmission of painful stimuli, with depression of the nervous reflex arc.

Reduction of cardiovascular risk and mortality: a population-based approach.

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.