PubMed Health⌕ Search

Biomedical subjects

Angelo Scuteri

Publications and source records attributed to Angelo Scuteri.

16 recordsLinked to original sources
PubMed2006

Heritability of cardiovascular and personality traits in 6,148 Sardinians.

In family studies, phenotypic similarities between relatives yield information on the overall contribution of genes to trait variation. Large samples are important for these family studies, especially when comparing heritability between subgroups such as young and old, or males and females. We recruited a cohort of 6,148 participants, aged 14-102 y, from four clustered towns in Sardinia. The cohort includes 34,469 relative pairs. To extract genetic information, we implemented software for variance components heritability analysis, designed to handle large pedigrees, analyze multiple traits simultaneously, and model heterogeneity. Here, we report heritability analyses for 98 quantitative traits, focusing on facets of personality and cardiovascular function. We also summarize results of bivariate analyses for all pairs of traits and of heterogeneity analyses for each trait. We found a significant genetic component for every trait. On average, genetic effects explained 40% of the variance for 38 blood tests, 51% for five anthropometric measures, 25% for 20 measures of cardiovascular function, and 19% for 35 personality traits. Four traits showed significant evidence for an X-linked component. Bivariate analyses suggested overlapping genetic determinants for many traits, including multiple personality facets and several traits related to the metabolic syndrome; but we found no evidence for shared genetic determinants that might underlie the reported association of some personality traits and cardiovascular risk factors. Models allowing for heterogeneity suggested that, in this cohort, the genetic variance was typically larger in females and in younger individuals, but interesting exceptions were observed. For example, narrow heritability of blood pressure was approximately 26% in individuals more than 42 y old, but only approximately 8% in younger individuals. Despite the heterogeneity in effect sizes, the same loci appear to contribute to variance in young and old, and in males and females. In summary, we find significant evidence for heritability of many medically important traits, including cardiovascular function and personality. Evidence for heterogeneity by age and sex suggests that models allowing for these differences will be important in mapping quantitative traits.

Adolescent↗
PubMed2006

Aortic correlates of clinical markers of large artery structure and function. Effects of aging and hypertension.

BACKGROUND AND AIMS: Non-invasive measures of large artery structure and function--such as aorto-femoral pulse wave velocity (PWV), arterial compliance (AC) and common carotid intima-media thickness (CCA IMT)--can predict new CV events, independently of traditional CV risk factors. However, neither their relations with aorta properties nor the effects of aging and hypertension on those relations are yet clear. METHODS AND RESULTS: 40 subjects (18 M, 22 F; mean age 60+/-16 yrs, range 21-83 yrs) free of any acute CV event, valve disease or atrial fibrillation, were studied. Aortic IMT, diastolic diameter (D) and distensibility (Dist) were measured by transesophageal echocardiography at three different levels: ascending aorta (AA), distal aortic arch (Aarc) and descending aorta (DA). PWV was measured by Complior. AC was measured as the ratio of stroke volume to pulse pressure. CCA IMT was measured by ultrasonography in diastole. The Dist, IMT, and D of each aortic segment were introduced alternatively into the regression models. After controlling for age, sex, traditional risk factors and prevalent CV disease, AC showed a significant positive association with the distensibility of proximal aortic segments, but no significant association with properties of distal aorta; PWV showed a significant positive association with proximal aorta wall thickness and a negative association with distal aorta distensibility; CCA IMT was positively associated with distal aorta wall thickness, but not with any explored property of the proximal aorta. None of these relationships differed between younger or older, normotensive or hypertensive subjects. CONCLUSIONS: Non-invasive measures of large artery structure and function are not equivalent with respect to their relations with aortic properties, so that AC seems to reflect proximal aorta function, PWV proximal aorta structure and distal aorta function, and CCA IMT distal aorta structure. Future studies are needed to confirm whether these relations identify a common pathogenetic mechanism, which may be the target for new therapeutic strategies.

Adult↗
PubMed2006

The association of genetic polymorphisms in sex hormone biosynthesis and action with insulin sensitivity and diabetes mellitus in women at midlife.

We evaluated associations of insulin sensitivity, metabolic syndrome, and diabetes mellitus with single nucleotide polymorphism (SNP) variants from sex hormone biosynthesis and action in women of 4 races/ethnicities. DNA was extracted from transformed cell samples of 1,538 women in the Study of Women's Health Across the Nation (SWAN). African American, Caucasian, Chinese, and Japanese women in SWAN enrolled in the Sex Steroid Hormone Genetics Protocol from whom fasting glucose and insulin measures (for estimating insulin sensitivity), diabetes status, and metabolic syndrome classification were obtained. SNPs from the genes encoding aromatase (CYP 19), 17beta-hydroxysteroid dehydrogenase (17HSD) type 1, and the estrogen receptors-alpha (ESR1) and -beta (ESR2) were measured. The prevalence of metabolic syndrome was 20% in Chinese women, 22% in Japanese women, 28% in Caucasian women, and 43% in African American women. The prevalence of diabetes was 3% in Chinese women, 4% in Japanese women, 7% in Caucasian women, and 19% in African American women. Significant associations of CYP 19 genotypes and insulin sensitivity were observed in African American, Caucasian, and Japanese women. Selected ESR1 and ESR2 genotypes were associated with insulin sensitivity and metabolic syndrome only in Japanese and Chinese women. The strongest associations related 17HSD genotypes to diabetes in Caucasian women, with odds ratios ranging from 4.4 to 7.5 and confidence intervals that excluded the null value. We observed strong associations between variations in sex hormone biosynthesis and function genes with insulin sensitivity, the metabolic syndrome, and diabetes that varied by race/ethnicity. The strong association of 17HSD and diabetes in Caucasian women has not been previously reported and should be further investigated.

17-Hydroxysteroid Dehydrogenases↗
PubMed2005

Ethnic variation in hypertension among premenopausal and perimenopausal women: Study of Women's Health Across the Nation.

Data are sparse regarding hypertension prevalence, treatment, and control among some ethnic groups of American women. Furthermore, the effects of ethnicity on hypertension, independent of other factors that vary with ethnicity, are poorly understood. We examined the prevalence of hypertension (defined as systolic > or =140 or diastolic > or =90 mm Hg or receiving treatment), treatment, and control (to <140/<90 mm Hg) in a multiethnic study of premenopausal and perimenopausal women. Stepwise multivariable logistic regression was used to select covariates associated with hypertension. Among 3292 women, 46.9% were white, 28.3% were black, 8.7% were Hispanic, 7.6% were Chinese, and 8.5% were Japanese. Among these 5 ethnic groups, respectively, there was substantial variation in prevalence of normal blood pressure levels (<120/<80 mm Hg; 59.9%, 35.4%, 16.8%, 67.2%, and 63.7%) and hypertension (14.5%, 38.1%, 27.6%, 12.8%, and 11.0%). After multivariable adjustment, hypertension prevalence was 2 to 3x higher among black and Hispanic women but similar among Chinese and Japanese women compared with white women. Among hypertensive participants, prevalence of antihypertensive treatment was highest among blacks (58.9%) and whites (55.2%) and lowest among Chinese (34.4%). Prevalence of control to goal blood pressure levels was highest among whites (43.0%) and Japanese (38.7%) and markedly lower among Hispanic women (11.4%). Compared with whites, black and Hispanic women have significantly higher prevalence of hypertension independent of other factors, whereas Chinese and Japanese women have similar prevalence. Treatment and control rates vary considerably across ethnicities. Greater efforts must be made to improve hypertension awareness, treatment, and control in all middle-aged women, particularly those in ethnic minority groups.

Adult↗
PubMed2005

Arterial aging: is it an immutable cardiovascular risk factor?

Age is the dominant risk factor for cardiovascular diseases. However, until recently, convincing mechanistic or molecular explanations for the increased cardiovascular risks conferred by aging have been elusive. Aging is associated with alterations in a number of structural and functional properties of large arteries, including diameter, wall thickness, wall stiffness, and endothelial function. Emerging evidence indicates that these age-associated changes are also accelerated in the presence of cardiovascular diseases, and that these changes are themselves risk factors for the appearance or progression of these diseases. In this review, the evidence demonstrating that arterial aging is accelerated in cardiovascular diseases and that accelerated arterial aging is a risk factor for adverse cardiovascular outcomes is briefly reviewed, and selected advances in vascular biology that provide insights into the mechanisms that may underlie the increased risks conferred by arterial aging are summarized. Remarkably, a host of biochemical, enzymatic, and cellular alterations that are operative in accelerated arterial aging have also been implicated in the pathogenesis and progression of arterial diseases. These vascular alterations are thus putative candidates that could be targeted by interventions aimed at attenuating arterial aging, similar to the lifestyle and pharmacological interventions that have already been proven effective. Therefore, the notion that aging is a chronological process and that its risky components cannot be modulated is no longer tenable. It is our hope that a greater appreciation of the links between arterial aging and cardiovascular diseases will stimulate further investigation into strategies aimed at preventing or retarding arterial aging.

Aging↗
PubMed2005

Effect of light-to-moderate alcohol consumption on age-associated arterial stiffening.

Increased thickness and stiffness of large arteries may contribute to why aging is the most important risk for cardiovascular diseases. Arterial stiffness, intimal medial thickness, and alcohol intake were measured in 563 subjects. A U-shaped relation was found between alcohol intake and a stiffness index, with the lowest index in moderate drinkers, which may partially explain the relation between alcohol and cardiovascular disease.

Adult↗
PubMed2005

apoE4 allele and the natural history of cardiovascular risk factors.

The aims of the present study were to compare the longitudinal changes in traditional cardiovascular (CV) risk factors (blood pressure, BMI, total and HDL-cholesterol, triglycerides, and blood glucose) in men with and without the apolipoprotein (apo)E4 allele. Three hundred six men from the Baltimore Longitudinal Study of Aging, ranging in age from 20 to 92 yr, were studied. Repeated measurements of CV risk factors were performed over a median follow-up time of 7 yr (maximum 14.3 yr) for men. Longitudinal changes in these CV risk factors were analyzed by linear mixed-effects models. The prevalence of the apoE4 allele was 25.5%. apoE4 was independently associated with accelerated changes over time in fasting plasma glucose (+9.5% vs. no change in those without apoE4 in the 6th age-decade over 10 yr). No significant effect of apoE4 on longitudinal changes in total or HDL-cholesterol, triglycerides, or blood pressures was observed. In conclusion, apoE4 influences fasting plasma glucose and its changes over time. This could explain, in part, the increased CV risk associated with the apoE4 genotype observed in men.

Adult↗
PubMed2005

Age-related changes in cognitive domains. A population-based study.

BACKGROUND AND AIMS: The aim of the present study is to describe the effects of aging on various cognitive domains (global cognitive function, executive function, motor speed) in a population sample of elderly men, and to describe how their age-related changes are influenced by education, depression, or prevalent cerebrovascular accidents (CEVD). METHODS: A cross-sectional observational study was conducted in a cohort of 334 men, 65 to 95 years old, living in rural communities, participating in the Italian cohort of two population studies--MATISS (Malattie cardiovascolari ATerosclerotiche Istituto Superiore di Sanità) and FINE (Finland, Italy, Netherlands, Elderly). Global cognitive function was measured by the Mini-Mental State Examination (MMSE), executive function by the Stroop test, motor speed by the Purdue Pegboard test, and depression by the CES-D test. Prevalence of cerebrovascular accidents (CEVD), myocardial infarction, and diabetes were evaluated by a questionnaire and a clinical examination. Blood pressure, and total and HDL cholesterol were measured. Current smoking status was self-reported. RESULTS: An age-associated decline in global cognitive functions, executive functions, and motor speed was observed. The decline is more apparent after the age of 85 for the MMSE, and after 75 for executive functions and motor speed. Logistic regression analysis revealed that age was independently associated with altered global cognitive functions, executive functions, and motor speed, even after adjusting for education, depression or prevalent CEVD. CONCLUSIONS: In a cohort of community-living elderly men aged 65 to 95 years, age-associated changes in mental functions are more evident after the age of 85. These changes are independent of education, depression, or prevalent CEVD.

Aged↗
PubMed2005

Arterial stiffness is an independent risk factor for cognitive impairment in the elderly: a pilot study.

BACKGROUND: Loss of cognitive function is a common condition in the elderly population. Cognitive impairment is defined as the transitional stage of cognitive decline, between normal aging and early dementia. We tested whether arterial stiffness, evaluated as pulse wave velocity (PWV), is associated with cognitive impairment in older subjects, and whether PWV is increased at a comparable extent in older subjects with cortical or subcortical cerebral lesions when compared with age-matched controls referred for memory deficits. SUBJECTS AND METHODS: Eighty-four subjects (78 +/- 5 years, 30 men and 54 women) referred for memory deficit with no history of stroke or atrial fibrillation were studied. Carotid-femoral PWV was determined non-invasively with Complior. The Mini Mental State Examination was assessed as a measure of global cognitive function. The sum of the score on the Activities of Daily Living and Instrumental Activities of Daily Living scales was used as a measure of personal independency. Based upon brain imaging, subjects were classified as referred for memory deficits with normal brain imaging, or control, with subcortical microvascular lesions or with cortical atrophy. RESULTS: PWV, normalized for mean blood pressure, was inversely correlated with the Mini Mental State Examination (r = -0.26, P < 0.05), even after controlling for education, prevalent cardiovascular (CV) disease, CV risk factors, and medication use (beta coefficient = -0.28, P < 0.01). PWV was also inversely correlated with personal independency (r = -0.36, P < 0.01; beta coefficient = -0.38, P < 0.01, after multiple adjustment). In the presence of no significant differences in age, education, traditional CV risk factor levels, carotid plaques, or prevalence of CV disease, higher PWV values were more frequent in subjects with cortical atrophy than in patients with subcortical microvascular lesions or controls (P < 0.05). CONCLUSIONS: PWV was associated with cognitive impairment and with a greater personal dependency, independently of major modifiable CV risk factors.

Aged↗
PubMed2005

The metabolic syndrome in older individuals: prevalence and prediction of cardiovascular events: the Cardiovascular Health Study.

OBJECTIVE: The prevalence of the metabolic syndrome, a potent risk factor for cardiovascular diseases (CVDs), has not been adequately explored in older individuals. Moreover, two sets of criteria have been proposed for the definition of metabolic syndrome, one by the World Health Organization (WHO) and one by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII). We therefore investigated the prevalence of this syndrome in a subgroup of older participants from the Cardiovascular Health Study (CHS) who were free of CVD at baseline. We also compared the prognostic significance of the two definitions of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 2,175 subjects from the CHS who were free of CVD at baseline and not taking antihypertensive or lipid-lowering medications were studied. Prevalence of the metabolic syndrome was assessed with both the WHO and ATPIII criteria. The incidence of coronary or cerebrovascular disease was ascertained during a median follow-up time of 4.1 years. RESULTS: Prevalence of the metabolic syndrome was 28.1% by ATPIII criteria and 21.0% by WHO criteria. The two sets of criteria provided concordant classification for 80.6% of participants. Multivariate Cox propotional hazard models showed that the metabolic syndrome defined with the ATPIII criteria, but not with the WHO criteria, was an independent predictor of coronary or cerebrovascular events and was associated with a 38% increased risk (hazard ratio 1.38 [95% CI 1.06-1.79], P < 0.01). CONCLUSIONS: Prevalence of the metabolic syndrome in older individuals is approximately 21-28% (depending on the definition used). The two sets of criteria have 80% concordance in classifying subjects. As defined by the ATPIII criteria, the metabolic syndrome yields independent prognostic information, even after adjusting for traditional cardiovascular risk factors and the individual domains of the metabolic syndrome.

Aged↗
PubMed2004

Association of mitral annulus calcification, aortic valve calcification with carotid intima media thickness.

BACKGROUND: Mitral annular calcification (MAC) and aortic annular calcification (AVC) may represent a manifestation of generalized atherosclerosis in the elderly. Alterations in vascular structure, as indexed by the intima media thickness (IMT), are also recognized as independent predictors of adverse cardiovascular outcomes. AIM: To examine the relationship between the degree of calcification at mitral and/or aortic valve annulus and large artery structure (thickness). METHODS: We evaluated 102 consecutive patients who underwent transthoracic echocardiography and carotid artery echoDoppler for various indications; variables measured were: systemic blood pressure (BP), pulse pressure (PP=SBP-DBP), body mass index (BMI), fasting glucose, total, HDL, LDL chlolesterol, triglycerides, cIMT. The patients were divided according to a grading of valvular/annular lesions independent scores based on acoustic densitometry: 1 = annular/valvular sclerosis/calcification absence; 2 = annular/valvular sclerosis; 3 = annular calcification; 4 = annular-valvular calcification; 5 = valvular calcification with no recognition of the leaflets. RESULTS: Patient score was the highest observed for either valvular/annulus. Mean cIMT increased linearly with increasing valvular calcification score, ranging from 3.9 +/- 0.48 mm in controls to 12.9 +/- 1.8 mm in those subjects scored 5 (p < 0.0001). In the first to fourth quartile of cIMT values the respective maximal percentual of score were: score 1: 76.1%, score 2: 70.1%, score 4: 54.3% and score 5: 69.5% (p > 0.0001). CONCLUSION: MAC and AVC score can identify subgroups of patients with different cIMT values which indicate different incidence and prevalence of systemic artery diseases. This data may confirm MAC-AVC as a useful important diagnostic parameter of systemic atherosclerotic disease.

Aged↗
PubMed2004

Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness.

OBJECTIVES: We sought to evaluate whether the clustering of multiple components of the metabolic syndrome (MS) has a greater impact on these vascular parameters than individual components of MS. BACKGROUND: Intima-media thickness (IMT) and vascular stiffness have been shown to be independent predictors of adverse cardiovascular events. The MS is defined as the clustering of three or more of the cardiovascular risk factors of dysglycemia, hypertension, dyslipidemia, and obesity. METHODS: Carotid IMT and stiffness were derived via B-mode ultrasonography in 471 participants from the Baltimore Longitudinal Study on Aging, who were without clinical cardiovascular disease and not receiving antihypertensive therapy. RESULTS: The MS conferred a disproportionate increase in carotid IMT (+16%, p < 0.0001) and stiffness (+32%, p < 0.0001), compared with control subjects. Multiple regression models, which included age, gender, smoking, low-density lipoprotein, as well as each individual component of MS as continuous variables, showed that MS was an independent determinant of both IMT (p = 0.002) and stiffness (p = 0.012). The MS was associated with a greater prevalence of subjects whose values were in the highest quartiles of IMT, stiffness, or both. CONCLUSIONS: Even after taking into account each individual component of MS, the clustering of at least three of these components is independently associated with increased IMT and stiffness. This suggests that the components of MS interact to synergistically impact vascular thickness and stiffness. Future studies should examine whether the excess cardiovascular risk associated with MS is partly mediated through the amplified alterations in these vascular properties.

Adult↗
PubMed2004

Prevalence of specific variant carotid geometric patterns and incidence of cardiovascular events in older persons. The Cardiovascular Health Study (CHS E-131).

OBJECTIVES: We hypothesized that variant geometric patterns of the common carotid artery (CCA) predict the incidence of cardiovascular disease (CVD), after accounting for CCA intima-medial thickness (IMT). BACKGROUND: Common carotid artery intima-media thickness has been associated with the incidence of cardiovascular disease. METHOD: Noninvasive measurements of IMT were made with high-resolution ultrasonography in 5,640 subjects 65 years of age or older participating in the Cardiovascular Health Study. New coronary and/or cerebrovascular events served as outcome variables over a median 10.2-year follow-up. To characterize different carotid structural geometric patterns (CGP), vascular mass (VM) was combined with the wall-to-lumen ratio (W/L). Normal values for W/L and VM were defined as age-adjusted, gender-specific 75th percentiles of the 1,899 normotensive subjects free of CVD at baseline. Four CGPs were defined: CGP1 = normal W/L ratio and VM; CGP2 = arterial remodeling (i.e., increased W/L ratio with normal VM); CGP3 = arterial hypertrophy (i.e., increased W/L ratio with increased VM); and CGP4 = arterial hypertrophy with dilation (i.e., normal W/L ratio and increased VM). RESULTS: Coronary or cerebrovascular events (adjusted for age, gender, traditional risk factors, and IMT) were associated with CGP in subjects free of CVD at baseline. Specifically, the hazard ratio (Cox proportional-hazards analyses) for CGP3 (arterial hypertrophy) was 1.25 (95% confidence interval [CI] 1.03 to 1.53), and for CGP4 (arterial hypertrophy with dilation) was 1.43 (95% CI 1.16 to 1.75) compared with CGP1 (normal). CONCLUSIONS: Arterial hypertrophy defined by variant CGP patterns is associated with the development of new CVD, independent of age, traditional risk factors, and CCA IMT.

Aged↗
PubMed2003

Nitric oxide inhibition as a mechanism for blood pressure increase during salt loading in normotensive postmenopausal women.

OBJECTIVES: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO), which plays an important role in natriuresis. We determined whether changes in endothelium-dependent vasodilation (EDD) and plasma ADMA predict changes in blood pressure (BP) after salt loading in normotensive postmenopausal women (PMW). METHODS: In 15 normotensive PMW (age 50-60 years), not receiving estrogen, ambulatory 24-h BP, plasma lipids, and ADMA were measured after 4 days of a low-salt diet (70 mEq/day) and following 7 days of high-salt intake (260 mEq/day). Brachial artery diameter at rest, during reactive hyperemia, i.e. EDD, and after sublingual nitroglycerin, i.e. non-EDD, were measured by ultrasound. The 24-h urinary NO metabolite (NOx) was measured by Griess reaction. Plasma ADMA was measured by high-pressure liquid chromatography. RESULTS: During low-salt, 24-h BP levels averaged 121 +/- 11 and 69 +/- 7 mmHg for systolic BP (SBP) and diastolic BP (DBP), respectively. After salt loading, average 24-h BP increases were: 7.6 mmHg for SBP, 2.2 mmHg for DBP, and 5.5 mmHg for pulse pressure (PP). Increases of 24-h SBP and 24-h PP after salt loading correlated directly with changes in ADMA (partial R2 = 0.16 for 24-h SBP and 0.17 for 24-h PP, P < 0.05 for both) and inversely with changes in EDD (partial R2 = 0.13, P = 0.09 for 24 h SBP and partial R2 = 0.15, P = 0.07 for 24-h PP), after adjustment for age and cholesterol. CONCLUSIONS: Inhibition of NO bioavailability by ADMA and a subsequent reduction in EDD contribute to the increase in BP during high-salt intake in normotensive PMW not receiving estrogen.

Arginine↗
PubMedDate not supplied

Blood pressure, arterial function, structure, and aging: the role of hormonal replacement therapy in postmenopausal women.

The occurrence of natural menopause may indicate that a woman is entering a period of increased risk for cardiovascular disease, due to both chronologic aging and lower levels of estrogen. This brief review aims to demonstrate the relevance of changes in blood pressure and large artery structure and function occurring after menopause. These changes, i.e., thickening and stiffening of large arteries (which, in turn would also result in increased systolic and pulse pressures), were found to predict subsequent cardiovascular events, independently of other known cardiovascular risk. The benefits of early hormone replacement therapy on the life expectancy of women have dramatically lost consensus since publication of the Womens Health Initiative study results. However, the authors believe that those results should increase the attention paid by clinicians and public health researchers to the individualization of hormone replacement therapy prescription for postmenopausal women, and to a better characterization of those vascular parameters and profiles identifying postmenopausal women who are most likely to benefit from specific hormone replacement therapy in terms of cardiovascular protection.

Adult↗