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.

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.

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.

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.

C-344T polymorphism of the aldosterone synthase gene and blood pressure in the elderly: a population-based study.

OBJECTIVES: Whether the C-344T polymorphism of the aldosterone synthase gene is important for blood pressure control remains controversial. It has been proposed that an association between this polymorphism and blood pressure might be evident in elderly subjects. The aim of the present study was to test this hypothesis in an epidemiological context. DESIGN: A cross-sectional epidemiological evaluation of a highly homogeneous unselected general population of elderly Caucasians. METHODS: Lifestyle, medical history, anthropometrics, skinfold thickness, supine blood pressure, heart rate and biochemical measures were recorded in 437 subjects aged > or = 65 years living in a secluded valley. All were genotyped for C-344T allele status and underwent measurements of plasma aldosterone and renin. RESULTS: The C-344T genotypic frequency did not deviate from Hardy-Weinberg equilibrium. The aldosterone to renin ratio was 19% lower in the CC than in the TT genotype. Systolic blood pressure was significantly lower in subjects with the CC genotype, higher in the TT (+9.6 mmHg versus CC) and intermediate in the CT (+7.9 mmHg versus CC). Adjustment for age, gender, smoking and antihypertensive treatment did not affect this association. Diastolic blood pressure did not differ across genotypes. A significant increase of systolic blood pressure with increasing age and with increasing skinfold thickness was observed in the TT homozygotes but not in the C-carriers. CONCLUSIONS: These data support the concept that the C-344T polymorphism plays a role in controlling systolic blood pressure and the age-related increase in systolic blood pressure in response to age and to body fat, possibly through differences in modulation of aldosterone synthesis.

Orthostatic hypotension does not increase cardiovascular risk in the elderly at a population level.

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.

Arterial stiffness and related variables across menopausal status: an epidemiologic study.

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.

High dietary fiber intake prevents stroke at a population level.

BACKGROUND & AIMS: This research was aimed at clarifying whether high dietary fiber intake has an impact on incidence and risk of stroke at a population level. METHODS: In 1647 unselected subjects, dietary fiber intake (DFI) was detected in a 12-year population-based study, using other dietary variables, anagraphics, biometrics, blood pressure, heart rate, blood lipids, glucose, insulin, uricaemia, fibrinogenaemia, erytrosedimentation rate, diabetes, insulin resistance, smoking, pulmonary disease and left ventricular hypertrophy as covariables. RESULTS: In adjusted Cox models, high DFI reduced the risk of stroke. In analysis based on quintiles of fiber intake adjusted for confounders, HR for incidence of stroke was lower when the daily intake of soluble fiber was >25 g or that of insoluble fiber was >47 g. In multivariate analyses, using these values as cut-off of DFI, the risk of stroke was lower in those intaking more that the cut-off of soluble (HR 0.31, 0.17-0.55) or insoluble (HR 0.35, 0.19-0.63) fiber. Incidence of stroke was also lower (-50%, p < 0.003 and -46%, p < 0.01, respectively). CONCLUSIONS: Higher dietary DFI is inversely and independently associated to incidence and risk of stroke in general population.

Cognitive Functions across the GNB3 C825T Polymorphism in an Elderly Italian Population.

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 test were performed in 220 elderly men and women free from clinical dementia and from neurological and psychiatric diseases randomly taken from the Italian general population and analysed across the C825T polymorphism. The performance of DS, immediate and delayed prose memory, 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 was maintained in the C-carriers but not in TT. In the case of prose memory, of memory 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.

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.

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.

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.

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.

German origin clusters for high cardiovascular risk in an Italian enclave.

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.