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Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease?

OBJECTIVES: We sought to determine clinical and laboratory correlates of calcification of the coronary arteries (CAs), aorta and mitral and aortic valves in adult subjects with end-stage renal disease (ESRD) receiving hemodialysis. BACKGROUND: Vascular calcification is known to be a risk factor for ischemic heart disease in non-uremic individuals. Patients with ESRD experience accelerated vascular calcification, due at least in part to dysregulation of mineral metabolism. Clinical correlates of the extent of calcification in ESRD have not been identified. Moreover, the clinical relevance of calcification as measured by electron-beam tomography (EBT) has not been determined in the ESRD population. METHODS: We conducted a cross-sectional analysis of 205 maintenance hemodialysis patients who received baseline EBT for evaluation of vascular and valvular calcification. We compared subjects with and without clinical evidence of atherosclerotic vascular disease and determined correlates of the extent of vascular and valvular calcification using multivariable linear regression and proportional odds logistic regression analyses. RESULTS: The median coronary artery calcium score was 595 (interquartile range, 76 to 1,600), values consistent with a high risk of obstructive coronary artery disease in the general population. The CA calcium scores were directly related to the prevalence of myocardial infarction (p < 0.0001) and angina (p < 0.0001), and the aortic calcium scores were directly related to the prevalence of claudication (p = 0.001) and aortic aneurysm (p = 0.02). The extent of coronary calcification was more pronounced with older age, male gender, white race, diabetes, longer dialysis vintage and higher serum concentrations of calcium and phosphorus. Total cholesterol (and high-density lipoprotein and low-density lipoprotein subfractions), triglycerides, hemoglobin and albumin were not significantly related to the extent of CA calcification. Only dialysis vintage was significantly associated with the prevalence of valvular calcification. CONCLUSIONS: Coronary artery calcification is common, severe and significantly associated with ischemic cardiovascular disease in adult ESRD patients. The dysregulation of mineral metabolism in ESRD may influence vascular calcification risk.

Adult↗

Insulin resistance and cardiovascular disease.

Cardiovascular risk factors cluster in obese individuals. Insulin resistance emerges as a common pathogenetic denominator underlying the risk factor cluster. Defects in nonesterified fatty acids metabolism have been implicated in the abnormal lipid and glucose metabolism which characterize the cluster. Other evidence also leads to the adipocyte as an important contributor to the risk factor cluster and cardiovascular complications through effects not only on fatty acids but also on leptin, plasminogen activator inhibitor-1, and angiotensinogen, to name a few. Fatty acids are elevated among abdominally obese individuals, are more resistant to suppression by insulin, and may contribute to hypertension. Fatty acids may affect blood pressure by inhibiting endothelial nitric oxide synthase activity and impairing endothelium-dependent vasodilation. Fatty acids increase alpha1-adrenoceptor-mediated vascular reactivity and enhance the proliferation and migration of cultured vascular smooth-muscle cells. Several effects of fatty acids are mediated through oxidative stress. Fatty acids can also interact with other facets of cluster, including increased angiotensin II, to accentuate oxidative stress. Oxidative stress, in turn, is implicated in the pathogenesis of insulin resistance, hypertension, vascular remodeling, and vascular complications. A clearer delineation of the key reactive oxygen signaling pathways and the impact of various interventions on these pathways could facilitate a rationale approach to antioxidant therapy and improved outcomes among the rapidly growing number of high-risk, insulin-resistant, obese individuals.

Cardiovascular Diseases↗

The association between periodontal diseases and cardiovascular diseases: a state-of-the-science review.

Early case-control and cross-sectional studies demonstrating associations between chronic periodontitis and cardiovascular disease (CVD) were quickly followed by secondary analyses of data available from existing longitudinal studies, which indicated that individuals with periodontitis, as determined by clinical measures, were at greater risk for CVD events. Many of these studies contained large numbers of subjects and were adjusted for traditional risk factors. Within the last 18 months, one case-control study and one longitudinal study have reported finding positive associations that were not statistically significant. The earlier studies stimulated a number of studies focused on identifying potential biological mechanisms that might underlie this association. While still early in that process, such studies have implicated a systemic role for oral microorganisms and for the quality and quantity of the host inflammatory response as key biologic processes that may underlie the association of CVD with the clinical manifestation of periodontitis. It is a positive development when changes in our knowledge regarding biologic mechanisms result in reevaluation of past studies, and this reevaluation leads to new studies that incorporate the design elements demanded by this new knowledge. In that spirit, we conclude that all longitudinal studies reported to date can be characterized as follows: none were initially designed to actually test the association of interest; almost all were restricted to clinical measures of periodontitis to index the exposure and lacked measures of infectious burden and host response; and they used a variety of cardiovascular clinical events to index the outcome and did not include subclinical measures of atherosclerosis. In addition, the longitudinal studies that failed to show a significant association between periodontitis and CVD used the least sensitive and crudest clinical measures of periodontal disease. Based upon the current state-of-the-science, all previous studies should be viewed as lacking sufficiently sensitive and comprehensive measures of periodontal disease as a systemic exposure. Since the potential health care impact of this relationship might be extensive, it is time to enter the next phase of research by conducting molecular epidemiology studies that are appropriately designed to test our current understanding of the molecular and cellular mechanisms involved.

Arteriosclerosis↗

Family history of heart disease and cardiovascular disease risk-reducing behaviors.

BACKGROUND: Family history is an important cardiovascular disease (CVD) risk factor. Preventive behaviors, including lifestyle modifications, can attenuate CVD risk. We studied the association between family history-based heart disease (HD) risk and CVD risk-reducing behaviors. METHODS: Using data from the 2001 Healthstyles survey, we compared frequencies of CVD risk-reducing behaviors among adults without known CVD in categories defined by family history-based HD risk. We classified respondents' HD risk as average (no first-degree relatives with HD), moderate (one relative), or high (> or = two relatives). Behaviors studied included lifestyle modifications, cholesterol measurement, and aspirin use. RESULTS: Of 3383 respondents without known CVD, 28% were classified as being at moderate risk and 15% as being at high risk for HD based on family history. Adjusted odds ratios indicated that moderate- and high-risk respondents were more likely to report having cholesterol measured within the previous 5 years (OR = 1.39, 95% Confidence Interval [CI] = 1.16-1.67 and 1.29, 95% CI = 1.01-1.64, respectively), and aspirin use to reduce CVD risk (OR = 1.49, 95% CI = 1.23-1.79 and 1.67, 95% CI = 1.33-2.09, respectively) than average-risk respondents. CONCLUSION: Almost one half of respondents reported a family history of HD. Aspirin use and cholesterol measurement (i.e., behaviors that health-care providers might suggest) were more likely to be reported by moderate- and high-risk respondents than were lifestyle changes. Family history merits further investigation as a public health tool to identify persons with increased HD risk who might benefit from enhanced prevention strategies.

Adolescent↗

Relation of borderline peripheral arterial disease to cardiovascular disease risk.

Peripheral arterial disease (PAD) is a well-established risk factor for clinical cardiovascular disease (CVD). The impact of a low ankle-brachial index (ABI), higher than the generally recognized 0.9 cutpoint for PAD, on CVD risk is not well characterized. We analyzed data from the 1999 to 2002 National Health and Nutrition Examination Survey (n = 4,895), a nationally representative sample of United States adults, to determine the prevalence of PAD (ABI <0.90), borderline PAD (ABI 0.90 to 0.99), a low-normal ABI (1.00 to 1.09), and a normal ABI (1.10 to 1.29), and the association of these ABI levels with CVD. The prevalence of PAD, borderline PAD, a low-normal ABI, and a normal ABI was 5.0%, 8.7%, 27.8%, and 54.8%, respectively. After age, race/ethnicity, and gender adjustment, the odds ratios of a 10-year coronary heart disease (CHD) risk of >or=20%, CHD, stroke, and CVD were higher at lower ABI levels (each p trend <0.01). After additional adjustment for potential confounders, the odds ratios associated with a low-normal ABI, borderline PAD, and PAD, compared with those with a normal ABI, were 1.24 (95% confidence interval [CI] 0.91 to 1.70), 1.34 (95% CI 0.99 to 1.83), and 1.87 (95% CI 1.29 to 2.73), respectively (p trend <0.001) for CVD and 1.20 (95% CI 0.82 to 1.77), 1.45 (95% CI 0.80 to 2.63), and 2.02 (95% CI 1.20 to 3.39), respectively (p trend = 0.015) for a 10-year risk of CHD of >or=20%. In contrast, a trend was not present for CHD and stroke after multivariate adjustment. In conclusion, subjects with a low-normal ABI or with borderline PAD need screening for CVD risk factors, and interventions may be appropriate to prevent cardiovascular events.

Adult↗

Impact of elevated blood pressure on mortality from all causes, cardiovascular diseases, heart disease and stroke among Japanese: 14 year follow-up of randomly selected population from Japanese -- Nippon data 80.

The objectives of the study were to clarify the relationship between blood pressure and mortality from stroke, heart disease, cardiovascular diseases and all causes of death among representative population of Japanese and to estimate category-specific excess mortality from stroke due to blood pressure (BP) level. The study design comprised a retrospective cohort study using the 1980 National Survey on Cardiovascular Diseases and identification of underlying causes of death using national vital statistics data. In 1994, a 14-year follow-up cohort study was conducted among participants of the National Survey on Cardiovascular Diseases in 1980, randomly selected from the Japanese population. With a collaboration of 300 public health centres, which had conducted the original survey in 1980, 91.4% of the participants of the original survey could be followed up. Total observed person-years were 53948 for men and 70932 for women. During follow-up, 1327 deaths were observed. BP levels were significantly related to mortality from strokes, cardiovascular diseases and all causes of death for both sexes (P<0.001). Heart disease mortality was significantly related to BP levels among men (P<0.05) while not among women. Estimated excess mortality was 130% for men and 42% for women and chiefly observed among moderate hypertensives (48% for men and 16% for women). In conclusion, high blood pressure was a risk factor for mortality from all causes as well as those from cardiovascular diseases, stroke and heart disease among Japanese. Since the major part of excess mortality was due to mild hypertension, a population strategy to reduce blood pressure should be encouraged.

Adult↗

Implications from and for food cultures for cardiovascular disease: diet, nutrition and cardiovascular diseases in China.

The change of lifestyle of Chinese people, along with the development of the national economy, has caused significant changes of the disease pattern in China. This includes the shift from predominantly communicable diseases to non-communicable diseases, such as cancer, cardiovascular disease, diabetes and obesity. This paper summarises epidemiology research results on the relationship between diet, nutrition and cardiovascular diseases (CVD) available in China. Most data used in this paper are from correlation studies. While the information is very useful in generating hypotheses on dietary and nutritional risk factors for CVD, both prospective studies and population-based intervention trials are needed to further verify these hypotheses. The information in this review clearly shows that diet and nutrition play important roles in the occurrence of CVD and hypertension in the Chinese population. Therefore, dietary means should be an important part of the strategies for the control of CVD and hypertension in China.

Cardiovascular Diseases↗

Gene therapy for cardiovascular disease.

Cardiovascular gene therapy has progressed to the point where clinical trials are now underway, in particular, for peripheral and myocardial ischemia and for restenosis. The delivery vectors are now more sophisticated--targeted to deliver genes only to specific tissues, and with gene expression regulated by disease-inducible promoters--which contributes to improved safety.

Animals↗

Nitric oxide synthase gene therapy for cardiovascular disease.

Gene therapy refers to the transfer of specific genes to the host tissue to intervene in a disease process, with resultant alleviation of the symptoms of a particular disease. Cardiovascular gene transfer is not only a powerful technique for studying the function of specific genes in cardiovascular biology and pathobiology, but also a novel and promising strategy for treating cardiovascular diseases. Since the mid-1990s, nitric oxide synthase (NOS), the enzyme that catalyzes the formation of nitric oxide (NO) from L-arginine, has received considerable attention as a potential candidate for cardiovascular gene therapy, because NO exerts critical and diverse functions in the cardiovascular system, and abnormalities in NO biology are apparent in a number of cardiovascular disease processes including cerebral vasospasm, atherosclerosis, postangioplasty restenosis, transplant vasculopathy, hypertension, diabetes mellitus, impotence and delayed wound healing. There are three NOS isoforms, i.e., endothelial (eNOS), neuronal (nNOS) and inducible (iNOS). All three NOS isoforms have been used in cardiovascular gene transfer studies with encouraging results. This review will discuss the rationale of NOS gene therapy in different cardiovascular disease settings and summarize the results of experimental NOS gene therapy from various animal models of cardiovascular disease to date.

Animals↗

The association between alcohol use and health behaviors related to the risk of cardiovascular disease: the South Carolina Cardiovascular Disease Prevention Project.

OBJECTIVE: This study examines the relationship between alcohol use and health behaviors related to the risk of cardiovascular disease (CVD). In particular, we examined the relationship between alcohol use and leisure time physical activity, participation in community physical activity programs and behaviors used for weight loss. Numerous studies have found a "protective" effect of moderate alcohol consumption on the risk of CVD. However, most of these studies have not adequately controlled for potential confounding by health behaviors associated with alcohol use. METHOD: We used descriptive and logistic regression analyses to examine cross-sectional survey data from 2,072 participants in the South Carolina Cardiovascular Disease Prevention Project. RESULTS: After controlling for age, race, education and preexisting CVD, moderate and heavy drinkers who do not smoke were more likely than nondrinkers to report engaging in regular leisure time physical activity. The relationship between other health behaviors and alcohol consumption was less clear. Among men, moderate and heavy drinkers were no more likely than nondrinkers to participate in community physical activity programs; among women, moderate and heavy drinkers were more likely than nondrinkers to report this activity. Moderate drinkers were more likely than nondrinkers to report that they were attempting to lose weight, however this difference was not statistically significant. CONCLUSIONS: These data suggest that at least some of the apparent protective effect of moderate alcohol consumption found in other studies may be due to differences between nondrinkers and drinkers with respect to physical activity and other health practices.

Adolescent↗

Does the nephrotic syndrome increase the risk of cardiovascular disease?

Cardiovascular mortality and morbidity were assessed, after a mean follow-up period of 5 years, in an unselected series of 159 adults presenting with the nephrotic syndrome between 1972 and 1975. 60% of the deaths were attributed to terminal renal failure, and the incidence of deaths from ischaemic heart-disease (IHD) was not significantly above normal. The proportion of patients experiencing angina and intermittent claudication and the prevalence of ischaemic electrocardiographic changes did not differ significantly from those of a London control population. At follow-up, hypertension was significantly more common (p less than 0.001) in male nephrotic patients than in controls. Earlier reports of a greatly increased incidence of IHD in unselected patients with the nephrotic syndrome were not confirmed. Routine treatment of hyperlipidaemia in the nephrotic syndrome is not, therefore, recommended.

Adolescent↗

Risk factors evaluation in some cardiovascular diseases.

Cardiovascular risk factors are associated with limitations of blood fluidity. Rheological behaviour of blood in transient flow may result from the internal organization, which in turn depends upon many parameters, which may be considered as possible elements of a profiling algorithm for diagnostic and prognostic values in various pathophysiological states. This study was designed to investigate haemorheological parameters in patients being treated for hypertension, coronary heart disease and myocardial infarct. On the basis of plasma viscosity, whole blood viscosity, haematocrit, red cell aggregation and red cell deformation, the risk was evaluated. In cases of hypertension there was a significant rise in plasma viscosity, whole blood viscosity, red cell aggregation and a fall in red cell deformability. In cases of coronary disease, plasma viscosity and red cell aggregation was increased, while in patients with myocardial infarcts, where the degree of severity is greater it was found that there was a significant rise in both plasma and whole blood viscosity. Haematocrit values were unaffected in all three groups.

Adult↗

Reduced dietary salt for prevention of cardiovascular disease.

BACKGROUND: Restricting sodium intake in elevated blood pressure over short periods of time reduces blood pressure. Long term effects (on mortality, morbidity or blood pressure) of advice to reduce salt in patients with elevated or normal blood pressure are unclear. OBJECTIVES: To assess in adults the long term effects (mortality, cardiovascular events, blood pressure, quality of life, weight, urinary sodium excretion, other nutrients and use of anti-hypertensive medications) of advice to restrict dietary sodium using all relevant randomised controlled trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, bibliographies of included studies and related systematic reviews were searched for unconfounded randomised trials in healthy adults aiming to reduce sodium intake over at least 6 months. Attempts were made to trace unpublished or missed studies and authors of all included trials were contacted. There were no language restrictions. SELECTION CRITERIA: Inclusion decisions were independently duplicated and based on the following criteria: 1) randomisation was adequate; 2) there was a usual or control diet group; 3) the intervention aimed to reduce sodium intake; 4) the intervention was not multifactorial; 5) the participants were not children, acutely ill, pregnant or institutionalised; 6) follow-up was at least 26 weeks; 7) data on any of the outcomes of interest were available. DATA COLLECTION AND ANALYSIS: Decisions on validity and data extraction were made independently by two reviewers, disagreements were resolved by discussion or if necessary by a third reviewer. Random effects meta-analysis, sub-grouping, sensitivity analysis and meta-regression were performed. MAIN RESULTS: Three trials in normotensives (n=2326), five in untreated hypertensives (n=387) and three in treated hypertensives (n=801) were included, with follow up from six months to seven years. The large, high quality (and therefore most informative) studies used intensive behavioural interventions. Deaths and cardiovascular events were inconsistently defined and reported; only 17 deaths equally distributed between intervention and control groups occurred. Systolic and diastolic blood pressures were reduced at 13 to 60 months in those given low sodium advice as compared with controls (systolic by 1.1 mm Hg, 95% CI 1.8 to 0.4, diastolic by 0.6 mm hg, 95% CI 1.5 to -0.3), as was urinary 24 hour sodium excretion (by 35.5 mmol/ 24 hours, 95% CI 47.2 to 23.9). Degree of reduction in sodium intake and change in blood pressure were not related. People on anti-hypertensive medications were able to stop their medication more often on a reduced sodium diet as compared with controls, while maintaining similar blood pressure control. REVIEWER'S CONCLUSIONS: Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. Evidence from a large and small trial showed that a low sodium diet helps in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

Antihypertensive Agents↗