Individual Cardiovascular Risk Factors Research Articles

Cardiovascular risk factors in patients aged 85 or older with ischemic stroke

Objectives To define a cardiovascular risk factor profile in very old patients with ischemic stroke. Patients and methods Data from a prospective hospital-based stroke registry was collected. Demographic characteristics and cardiovascular risk factors in individuals aged 85 years or older with ischemic stroke ( n = 303) were compared with patients under 85 years ( n = 1537). Results The study population accounted for 16.5% of all cases of ischemic stroke. The mean (S.D.) age was 88.2 (2.8) years (70% women). Hypertension occurred in 44.9% of patients, atrial fibrillation in 42.6%, diabetes in 16.2%, and congestive heart failure in 15.5%. The most frequent stroke subtypes were cardioembolic (36%) and atherothrombotic (31.4%) infarction. Congestive heart failure (odds ratio [OR] = 3.62), chronic renal disease (OR = 2.54), female sex (OR = 2.27), previous cerebrovascular disease (OR = 1.71), and atrial fibrillation (OR = 1.38) were significantly associated with ischemic stroke, whereas diabetes (OR = 0.68), hypertension (OR = 0.61), hyperlipidemia (OR = 0.45), and heavy smoking (OR = 0.21) occurred more frequently in patients under 85 years. Conclusion Adequate treatment of potentially modifiable risk factors, including congestive heart failure, chronic renal disease, and atrial fibrillation may contribute to prevent ischemic stroke in very old people.

Microalbuminuria in pediatric obesity: prevalence and relation to other cardiovascular risk factors

Microalbuminuria (MA) has emerged as a strong predictor of cardiovascular (CV) events, even in nondiabetic adults. While the mechanisms behind this association remain to be established, most studies suggest that MA is the result of increased vascular leakage denoting endothelial dysfunction associated with early vasculopathy. To examine if a urine albumin creatinine ratio (UACR) in the microalbuminuric range is related to metabolic markers of CV risk in obese and pre-diabetic youth recruited from an obesity clinic. MA was defined as a UACR between 2.0 and 20 mg/mmol. Subjects with gross proteinuria (UACR>20 mg/mmol) were excluded from the study. Analyses were performed to assess the relationship of MA and markers of CV risk, including body mass index (BMI), % body fat, blood pressure (BP), lipid profile, inflammatory markers, insulin sensitivity indexes and degrees of oral glucose tolerance. MA was also correlated with risk factor constellations unique to the metabolic syndrome, a distinct CV risk entity. Postchallenge alterations in glucose metabolism and overall loss in insulin sensitivity were strongly and positively correlated with the presence of MA (P = 0.002 and 0.01, respectively). Neither the metabolic syndrome nor any of the individual CV risk factors examined were associated with MA. These data suggest that early glucose toxicity, as reflected by postchallenge elevations in plasma glucose even below the diagnostic cutoff for diabetes mellitus may contribute to the presence of MA. Whether MA is equally as predictive of CV disease in youth, as in adulthood, remains to be investigated.

Cardiovascular Risk Factors May Moderate Pharmacological Treatment Effects in Major Depressive Disorder

An increased association between depression and cardiovascular disease, as well as cardiovascular risk factors, led to the "vascular depression" hypothesis. This subtype of depression is postulated to have a different clinical presentation and to be more treatment-resistant. In this study, we measured the impact of cardiovascular risk factors on the outcome of antidepressant treatment in major depressive disorder (MDD). We enrolled 348 MDD subjects, ages 19 to 65 years, in an 8-week treatment study with 20 mg fluoxetine per day. We recorded for each subject 6 cardiovascular risk factors: age (male > or =45, female > or =55), smoking, family history, hypertension, diabetes, hypercholesterolemia; and we defined a cardiovascular risk score (range, 0-6) by the number of risk factors present. Treatment outcome was measured as response (> or =50% improvement on the 17-item Hamilton Rating Scale for Depression [Ham-D-17]) and remission (final Ham-D-17< or =7). In logistic regression analyses, the cardiovascular risk score was significantly associated with treatment nonresponse and lack of remission when adjusting for age of onset of MDD and baseline severity of depression. The cardiovascular risk score remained significantly associated with treatment nonresponse when we additionally controlled for overall medical burden (measured with the Cumulative Illness Rating Scale). Among individual cardiovascular risk factors, elevated total cholesterol was a significant predictor of treatment nonresponse and lack of remission. Cardiovascular risk factors may have negative effects on the course of treatment in MDD. These results support the concept of "vascular depression" in younger subjects.

Glycemic Control, Atherosclerosis, and Risk Factors for Cardiovascular Disease in Individuals With Diabetes

Glycemic control (HbA(1c) [A1C]) is strongly associated with microvascular disease in individuals with diabetes, but its relation to macrovascular disease and atherosclerosis is less clear. This study examines the relationship between A1C, carotid intima-media thickness (IMT), and traditional cardiovascular risk factors in individuals with diabetes. A cross-sectional study of 2,060 people with diagnosed and undiagnosed (unrecognized) diabetes in the Atherosclerosis Risk in Communities study was performed. LDL and HDL cholesterol, plasma triglycerides, and waist-to-hip ratio were significantly associated with A1C after multivariable adjustment. African Americans with undiagnosed and diagnosed diabetes had significantly elevated A1C values compared with whites, even after adjustment for potentially confounding factors. There was a graded association between A1C and carotid IMT. In a fully adjusted model in individuals with undiagnosed diabetes, the odds ratio (OR) of being in the highest quartile of IMT versus the lowest was 2.46 (95% CI 1.16-5.03, comparing the highest quartile of A1C to the lowest). In people with diagnosed diabetes, the comparable OR was 2.62 (1.36-5.06). This study identified several important associations between A1C and known risk factors for cardiovascular disease and suggested that A1C is independently related to carotid IMT. Chronically elevated glucose levels may contribute to the development of atherosclerosis in people with diabetes, independent of other risk factors.

W02-P-015 Novel cardiovascular risk factors in individuals with family history of premature atherosclerotic disease

This study sought to determine the effects of endogenous tetrahydrobiopterin (BH4) bioavailability on endothelial nitric oxide synthase (eNOS) coupling, nitric oxide (NO) bioavailability, and vascular superoxide production in patients with coronary artery disease (CAD).GTP-cyclohydrolase I, encoded by the GCH1 gene, is the rate-limiting enzyme in the biosynthesis of BH4, an eNOS cofactor important for maintaining enzymatic coupling. We examined the associations between haplotypes of the GCH1 gene, GCH1 expression and biopterin levels, and the effects on endothelial function and vascular superoxide production.Blood samples and segments of internal mammary arteries and saphenous veins were obtained from patients with CAD undergoing coronary artery bypass grafting (n = 347). The GCH1 haplotypes were defined by 3 polymorphisms: rs8007267G<A, rs3783641A<T, and rs10483639C<G (X haplotype: A, T, G; O haplotype: any other combination). Vascular superoxide (± the eNOS inhibitor NG-nitro-L-arginine methyl ester [L-NAME]) was measured by lucigenin-enhanced chemiluminescence, whereas the vasorelaxations of saphenous veins to acetylcholine were evaluated ex vivo.Haplotype frequencies were OO 70.6%, XO 27.4%, and XX 2.0%. The X haplotype was associated with significantly lower vascular GCH1 messenger ribonucleic acid expression and substantial reductions in both plasma and vascular BH4 levels. In X haplotype carriers both vascular superoxide and L-NAME–inhibitable superoxide were significantly increased, and were associated with reduced vasorelaxations to acetylcholine.GCH1 gene expression, modulated by a particular GCH1 haplotype, is a major determinant of BH4 bioavailability both in plasma and in the vascular wall in patients with CAD. Genetic variation in GCH1 underlies important differences in endogenous BH4 availability and is a determinant of eNOS coupling, vascular redox state, and endothelial function in human vascular disease.

Differences between carotid wall morphological phenotypes measured by ultrasound in one, two and three dimensions

Ultrasound measurements are both surrogate markers and risk factors for atherosclerosis end points. Carotid intima-media thickness (IMT) is most commonly used, but ultrasound can also define structures in higher spatial dimensions, such as total plaque area (TPA) and total plaque volume (TPV). Because there are minimal data regarding the relationship between IMT, TPA and TPV, we measured these variables in 272 Oji-Cree subjects. We found pairwise correlations for IMT:TPA, IMT:TPV and TPA:TPV of 0.507, 0.588 and 0.846, respectively (transformed variables, all P < 0.0001). In a subset of 168 subjects with complete cardiovascular risk factor data, we performed multivariate regression analysis to identify sources of variation for IMT, TPA and TPV. We found that the ultrasound traits showed different correlations with individual cardiovascular risk factors. In particular, IMT was significantly associated with hypertension, TPA with smoking and plasma cholesterol, and TPV with diabetes. Therefore, these ultrasound measures of carotid artery morphology, while somewhat correlated, likely represent distinctive quantitative traits with different biological determinants, as underscored by different risk factor associations in the multivariate regression analysis. Because the measurements have different implications and determinants, investigators might need to be selective about the particular measurements they choose for specific applications.

Cross-sectional evaluation of brachial artery flow-mediated vasodilation and C-reactive protein in healthy individuals.

The present study was designed to (a) examine the interrelationship between endothelial function and CRP in healthy individuals and (b) evaluate the relationship of each biomarker towards global Framingham risk scores. Brachial artery flow-mediated vasodilatation (FMD), CRP, and traditional cardiovascular risk factors were measured in the Firefighters and Their Endothelium (FATE) study, which recruited 1154 male participants (mean age 47.4+/-9.8 years) with no known history of cardiovascular disease. No relationship was observed between FMD and CRP (p = 0.96). FMD and the Framingham risk score tended to correlate but not significantly (p = 0.07). A lower FMD was related to a higher systolic and diastolic blood pressure (p < 0.001 and p = 0.002, respectively) in the univariate analysis, and higher systolic blood pressure (p = 0.001) in the multivariate analysis. Elevated CRP levels independently correlated most closely with overall Framingham risk score (r = 0.36, p < 0.001) and a weaker although statistically significant relationship was seen with individual traditional cardiovascular risk factors (p < 0.005). The current study provided evidence that brachial artery FMD had no relationship to CRP in a large cohort of healthy subjects. These observations suggest that the predictive value of CRP may be largely independent of abnormalities in endothelial function. The additive prognostic value of endothelial vasodilator testing remains to be established.

Longitudinal studies in the prevention of cardiovascular diseases

Longitudinal studies of well defined cohorts have contributed to the identification of risk factors of coronary heart disease and other clinical complications of atherosclerosis. After commenting on the conclusions of experimental atherosclerosis and risk factors suggested by the study of a series of myocardial infarction in young adults and their matched controls, we discuss the methodology, management and results of longitudinal studies carried out in the United States since 1949: Twin Cities, Framingham, Pooling Project, Western Collaborative, Puerto Rico Evans County, NI-IION-SAN, San Francisco, Harvard, Bogalusa and CARDIA. Special attention is given to the hypothesis proposed at the beginning of the Framingham Study and the obstacles and changes to continue the project after the first twenty-four years. We also expose the Seven Countries Study, designed and managed by Ancel Keys, as the first study performed with centralized methodology in various countries, and the studies in various European countries: Whitehall, Manresa, Paris, British Regional, Northwick Park, Caerphilly, Speedwell and PROCAM. We analyse the role of the longitudinal studies in the methodology of later studies: sons and daughters of the Framingham participants, longitudinal studies based on questionnaires, studies of the other risk factors, prevalence of risk factors in retrospective studies, trials of primary prevention (MRFIT, WHO European Collaborative Trial and Gotenburg Study) and the participation of the trained teams in the MONICA Project. We present the issues still under debate in connection with the methodology and results of the longitudinal studies: problems in the periodic examination of the participants in the epidemiologic studies, changes in definition of the new cases of acute cardiovascular events, use and selection of risk functions based on coronary charts to calculate the individual risk and cardiovascular risk factors as yet unknown.

Relative influence of diet and physical activity on cardiovascular risk factors in urban Chinese adults.

The relative influence of dietary factors vs physical activity on cardiovascular risk factors are poorly understood. We investigated these factors in a population whose traditional diet may have both positive (high plant-based) and negative (high refined carbohydrate) aspects, and whose physical activity levels (PALs) vary widely. Cross-sectional study. A total of 130 weight stable adults aged 35-49 y (BMI 18-35 kg/m(2)) living in urban Beijing, China. Dietary intake (by food frequency questionnaire), PAL as the ratio of predicted total to resting energy expenditure), percent body fat (by deuterium oxide dilution), and central adiposity (waist circumference and waist to hip ratio) were assessed. Biochemical parameters (total cholesterol, low- and high-density lipoprotein cholesterol (LDL-C; HDL-C), triglyceride (TG), apolipoproteins A-I and B, glucose, insulin, and homocysteine and its related vitamins), blood pressure and presence of the metabolic syndrome (having >/=3 risk factors of central adiposity, HDL-C, TG, glucose, blood pressure) were also examined. Mean values for cardiovascular risk factors were relatively low, but 19% of subjects had the metabolic syndrome. Using validated methods for measuring food intake and energy expenditure, we found that an adverse cardiovascular risk profile was associated with a diet high in carbohydrate, low in polyunsaturated fat, and low in fruit and vegetables, independent of body fatness and its distribution. While dietary factors predicted individual cardiovascular risk factors more consistently than PAL, avoidance of low PAL reduced the risk of having the metabolic syndrome. These results suggest that, regardless of total body fatness and fat distribution, multiple unfavorable dietary factors and low physical activity independently increase the risk for cardiovascular disease. Avoidance of a sedentary lifestyle additionally reduces the risk of developing the metabolic syndrome.

The influence of calcium and magnesium in drinking water and diet on cardiovascular risk factors in individuals living in hard and soft water areas with differences in cardiovascular mortality.

BackgroundThe role of water hardness as a risk factor for cardiovascular disease has been widely investigated and evaluated as regards regional differences in cardiovascular disease. This study was performed to evaluate the relation between calcium and magnesium in drinking water and diet and risk factors for cardiovascular disease in individuals living in hard and soft water areas with considerable differences in cardiovascular mortality.MethodsA random sample of 207 individuals living in two municipalities characterised by differences in cardiovascular mortality and water hardness was invited for an examination including a questionnaire about health, social and living conditions and diet. Intake of magnesium and calcium was calculated from the diet questionnaire with special consideration to the use of local water. Household water samples were delivered by each individual and were analysed for magnesium and calcium.ResultsIn the total sample, there were positive correlations between the calcium content in household water and systolic blood pressure (SBP) and negative correlations with s-cholesterol and s-LDL-cholesterol. No correlation was seen with magnesium content in household water to any of the risk factors.Calcium content in diet showed no correlation to cardiovascular risk factors. Magnesium in diet was positively correlated to diastolic blood pressure (DBP). In regression analyses controlled for age and sex 18.5% of the variation in SBP was explained by the variation in BMI, HbA1c and calcium content in water. Some 27.9% of the variation in s-cholesterol could be explained by the variation in s-triglycerides (TG), and calcium content in water.ConclusionsThis study of individuals living in soft and hard water areas showed significant correlations between the content of calcium in water and major cardiovascular risk factors. This was not found for magnesium in water or calcium or magnesium in diet. Regression analyses indicated that calcium content in water could be a factor in the complexity of relationships and importance of cardiovascular risk factors. From these results it is not possible to conclude any definite causal relation and further research is needed.

Hepatic expression of microsomal triglyceride transfer protein and in vivo secretion of triglyceride-rich lipoproteins are increased in obese diabetic mice.

Secondary hyperlipidemia is a major cardiovascular risk factor in individuals with type 2 diabetes. Increased hepatic production of apolipoprotein B (apoB)-containing lipoproteins contributes to the elevated plasma levels, but the mechanism is poorly understood. Recent results have established that microsomal triglyceride transfer protein (MTP) is rate limiting for the assembly and secretion of apoB-containing lipoproteins. To better understand the mechanism of type 2 diabetes-associated hyperlipidemia, we quantified hepatic MTP mRNA levels, hepatic microsomal triglyceride transfer activity, and in vivo triglyceride secretion from the liver in two diabetic mouse models. Obese diabetic (ob/ob) mice had 45% higher (P = 0.006) hepatic MTP mRNA levels, 54% higher (P < 0.0001) microsomal triglyceride transfer activity, and 70% higher (P < 0.0001) in vivo triglyceride secretion rates compared with ob/+ control mice. In contrast, in lean streptozotocin-treated diabetic mice, hepatic MTP mRNA levels were unchanged, whereas microsomal triglyceride transfer activity and in vivo triglyceride secretion rates were marginally decreased. These studies suggest that obesity-induced type 2 diabetes in mice confers increases in hepatic MTP expression and secretion of triglyceride-rich lipoproteins. High blood glucose and altered hepatic expression of sterol regulatory element binding protein genes play a minor role in this diabetic response.

Insights from a large rural population laboratory: Health census `89 and `99

PURPOSE: Data are limited on health status behaviors and use of health services for rural residents. Yet rural areas now have higher rates of chronic diseases, such as coronary heart disease, than urban areas.METHODS: A population laboratory (Health Census) was established in rural Central NY (Otsego County) to study these variables in this population. HC `89 was a door-to-door enumeration of all permanent households in the country. In 1989, 44,500 adults in 18,000 households provided data on individual health screenings, cancer and cardiovascular risk factors, health behaviors, chronic disease, access to care, preventive services use, health insurance and emergency department utilization. Data collection for HC `99 will identify 10-year trends; it also includes baseline data for children. Also, households in six surrounding rural counties (N = 10,000) were sampled; cost benefits of different survey methods were assessed. Questions about perceived health status, and special health and pediatric preventive care needs were included. After 10 years of social change, many limitations of traditional survey methods became apparent; much more varied and frequent types of follow-up were needed to achieve adequate response rates.RESULTS: The HC `89 final response rate was 86%. There were significant socioeconomic gradients in use of preventive services (blood pressure screening, rectal exams, mammograms and Pap smears). Adults without health insurance or Medicaid had much lower utilization rates of screening tests and higher rates of cigarette smoking and obesity. Several community intervention programs were implemented as a result of HC `89. HC `99 provides additional analyses to examine change in preventive service use, self-reported chronic disease, and health services use; it will likely verify the persistence of socioeconomic gradients. Response rates are similar to `89, but achieved only with more intensive reinforcement.CONCLUSIONS: HC `89 confirmed a lag in positive health indices in rural populations in Central NY. Both newer methodologies now needed and results of HC `99 will serve as guides for smaller rural counties to develop affordable local health surveys and plan intervention strategies.

Lack of association between lipaemia and central adiposity in subjects with an atherogenic lipoprotein phenotype (ALP).

To investigate the associations between indices of adiposity and cardiovascular risk factors in individuals with an atherogenic lipoprotein phenotype (ALP). Fifty-five men, aged 34-69 y, body mass index (BMI) 22-35 kg/m2, with an ALP lipid profile (triglycerides (TG) 1.5-4.0 mmol/l, HDL<1.1 mmol/l; %LDL-3>40% total LDL). Each participant provided a fasting blood sample and underwent an 8 h postprandial assessment and had anthropometric measurements taken. BMI, waist circumference (W), waist-to-hip ratio (W/H), sum of skinfolds (SSK), fasting and postprandial concentrations of glucose, insulin and plasma lipids, post-heparin lipase activity, and apoE genotype. The expected positive associations between BMI, W and SSK and fasting and postprandial insulin were observed (r=0.42-0.65). Little association between glucose responses and any measures of adiposity was evident. Unexpectedly, there were no positive associations between measures of central adiposity (W and W/H) and fasting and postprandial TG responses, with a trend towards negative associations in this study group (TG AUC vs W, r=-0.23, P=0.097; TG IAUC vs W/H, r=-0.26, P=0.068). Subgroup analysis indicated that lack of a positive association between central adiposity and postprandial TG values was more evident in those with one E4 allele (r=-0.42, P=0.077) relative to non-E4 carriers (r=-0.16, P=0.430). The expected positive associations between insulin and TG responses were not observed (r=-0.03 to -0.36). In this ALP group the expected positive association between TG responses and a centralized distribution of body fat was not observed, particularly in individuals with an apoE4 genotype. Our findings are not in line with the view that there is a clear causal relationship between insulin resistance and the lipid abnormalities associated with ALP.

Early endothelial dysfunction in adults at risk from atherosclerosis: different responses to l-arginine

Objectives. We sought to examine endothelial responses to l-arginine in three groups with isolated risk factors: hypercholesterolemia, smoking and insulin-dependent diabetes mellitus (IDDM).Background. Endothelial dysfunction occurs early in atherosclerosis, predating clinical disease. We hypothesized that the nature of endothelial injury associated with individual cardiovascular risk factors might be different and that this might affect the response to l-arginine, the substrate for endothelial nitric oxide synthase.Methods. We studied the effects of intravenous l-arginine on brachial artery flow-mediated dilation (FMD) and glyceryl trinitrate (GTN)–mediated dilation in 36 young subjects (18 to 40 years old) without clinical atherosclerosis: 9 each of normal control subjects, hypercholesterolemic subjects, cigarette smokers and subjects with IDDM.Results. Baseline FMD was significantly impaired in hypercholesterolemic subjects (mean ± SD 1.7 ± 2.3%), smokers (1.6 ± 1.8%) and diabetic subjects (1.8 ± 1.5%) compared with that in control subjects (6.9 ± 3.3%, p = 0.001). The response to GTN was not significantly different between the subjects with risk factors and control subjects, apart from those with IDDM, in whom it was significantly impaired (p = 0.026). After infusion of l-arginine, there was no change in FMD in control or diabetic subjects. In hypercholesterolemic subjects and smokers, FMD improved from 1.9 ± 1.9% to 4.1 ± 2.1% (p = 0.01) and from 2.0 ± 1.71% to 3.1 ± 2.5% (p = 0.02), respectively.Conclusions. FMD was impaired in all three risk factor groups; however, they responded differently to l-arginine, FMD being improved in hypercholesterolemic subjects and smokers but unchanged in diabetic subjects. These results indicate differing underlying pathophysiologies that may facilitate the design of treatment strategies for subjects with different risk factors.