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Carotid intima-media thickness as a surrogate marker for cardiovascular disease in intervention studies.

BACKGROUND: Cardiovascular trials using clinical endpoints to assess efficacy typically require follow-up of large numbers of participants for 3-5 years. This disadvantage has encouraged the search for well-validated surrogate markers for cardiovascular disease (CVD). These markers may provide earlier indications of efficacy in trials involving fewer participants. One approach gaining interest in recent years is the measurement of atherosclerotic progression, a major underlying cause of CVD. SCOPE: This review article aims to further substantiate the evidence supporting the use of measurement of carotid intima-media thickness (CIMT) as a surrogate marker for atherosclerosis and cardiovascular risk. FINDINGS: CIMT has consistently been related to future CVD events in population studies. CIMT is significantly related with other markers for CVD risk, such as elevated levels of risk factors and presence of atherosclerosis in the coronary arteries. Furthermore, almost all lipid-lowering trials and a large number of blood pressure lowering trials have consistently shown a reduction in progression of CIMT. In addition, the ultrasound technique for measuring CIMT is safe and highly reproducible. CONCLUSION: Thus, CIMT may be used as a surrogate endpoint in clinical trials to enable the benefits of new therapies or regimens to be more rapidly translated into clinical practice.

Biomarkers↗

Mother-daughter correlations of obesity and cardiovascular disease risk factors in black and white households: the NHLBI Growth and Health Study.

OBJECTIVES: This study sought to evaluate obesity as a potential explanatory factor for the increased relative risk for cardiovascular disease in Black compared with White women. METHODS: Familial associations for obesity and cardiovascular disease risk factors were assessed in 720 White and 580 Black mother-daughter pairs from the National Heart, Lung, and Blood Institute's Growth and Health Study by using Pearson's chi square, Spearman's correlations, and partial correlations. RESULTS: Black girls and mothers were significantly heavier and had higher body mass indices than their White counterparts. In each racial group, significant, positive mother-daughter correlations existed for weight, body mass index, and triceps skinfolds, and for all cardiovascular disease risk factors. Obesity measures correlated positively with systolic blood pressure and triglycerides and inversely with high-density lipoprotein cholesterol in girls and mothers of both races. Correlations between mothers and daughters for exercise and ideal body shape were weak and did not explain obesity associations. CONCLUSIONS: Intrafamilial associations of obesity, cardiovascular disease risk factors, and the obesity-cardiovascular disease risk factor relationship support the position that increased cardiovascular disease morbidity and mortality rates in Black women may be linked to excess obesity in Black women compared with White ones.

Black or African American↗

Emergence of the concept of cardiovascular disease.

Historically, the concept of cardiovascular disease is a recent and evolving concept. Well into the eighteenth century, cardiac and vascular diseases were little known and considered a rarity. Description of the circulation by William Harvey (1578-1657) in 1628 marks the beginning of the changes that ensued. However, knowledge was slow to accrue and not until the nineteenth century was the heart taken as a specific object of study. The description of end-stage kidney disease by Richard Bright (1789-1858) in 1827 launched studies of the vasculature, which were to lead to the recognition of hypertension and subsequent identification of the lesions of arteriosclerosis (1833) and atherosclerosis (1904) as diseases of the vasculature. Only between the two world wars did the full impact of these lesions on mortality and morbidity come to be finally recognized. Their study and therapy has defined much of the profound changes that affected twentieth century medicine.

Cardiology↗

Cardiovascular disease in elderly in-patients at the Kenyatta National Hospital, Nairobi-Kenya.

A prospective study to determine the prevalence and profile of cardiovascular disease in elderly patients admitted into the medical wards, Kenyatta National Hospital, was carried out between July 1991 and January 1992. Two hundred and two patients over 60 years of age were admitted into the medical wards over this period. This formed seven per cent of the total medical admissions. Two of these refused to take part in the study. Of the 200 elderly patients evaluated for cardiovascular disease, 146 (73%) were between 60 and 75 years of age with only 26 (13%) being over 85 years. Fifty seven per cent were males. Clinical evidence of cardiovascular disease was present in 79 (39.5%) of the patients evaluated. There was no sex difference in the prevalence of cardiovascular disease as judged from clinical evaluation (37.7% males versus 41.9% females, p > 0.05). Cardiovascular diseases in our medical in-patients at Kenyatta National Hospital are common and especially so with hypertension which plays an important role in the aetiology of congestive heart failure and cerebravascular accidents. Cardiac arrhythmias are also common though not necessarily symptomatic. Rheumatic heart disease and cardiomyopathies were uncommon in our study population. A community-based survey is needed to determine the true prevalence of cardiovascular diseases in the elderly and their contribution to morbidity in this sector of the population.

Age Distribution↗

All-cause mortality and cardiovascular disease mortality in three American Indian populations, aged 45-74 years, 1984-1988. The Strong Heart Study.

Community mortality surveillance for 1984-1988 was conducted by researchers of the Strong Heart Study, which examined the incidence, prevalence, and risk factors of cardiovascular disease in three American Indian populations, aged 45-74 years, in Arizona, Oklahoma, and South/North Dakota. All-cause and cardiovascular disease mortality rates were determined through the use of death certificate data. Cardiovascular disease deaths were confirmed by independent systematic review of medical records. In all three populations, men had higher all-cause and cardiovascular disease mortality rates than did women. Oklahoma exhibited slightly lower 5-year, age-adjusted, all-cause mortality (96/1,000) than did Arizona (107/1,000) and South/North Dakota (114/1,000). The leading cause of death among both sexes in Oklahoma and in South/North Dakota was cardiovascular disease. Diabetes mellitus led among Arizona women. The other major causes of death were cancer, liver disease including cirrhosis, and injury. When compared with the rates in each state, average annual all-cause mortality rates were higher for the American Indian populations in almost every age group. The all-cause annual mortality rates in the three Indian populations were close to rates in the US black population and higher than the rates of the entire US population and of US whites. This trend was amplified in the 45- to 64-year age group. Only in the 65- to 74-year age group did mortality rates in the Indian population approach those of the US population. Cardiovascular disease mortality rates were close to the US averages in Arizona and Oklahoma, but they were more than two times higher in South/North Dakota among those between 45 and 64 years of age. Thus, American Indians in Arizona, Oklahoma, and South/North Dakota exhibit high all-cause mortality rates. In particular, the South/North Dakota population cardiovascular disease death rate appears to present a potential target for community-based programs to intervene on known risk factors to promote healthy lifestyles.

Aged↗

Hemostatic factors and cardiovascular disease in active rheumatoid arthritis: an 8 year followup study.

OBJECTIVE: To investigate the prospective effect of hemostatic factors and inflammatory variables on the progression of cardiovascular disease in rheumatoid arthritis (RA). METHODS: Von Willebrand factor (vWF) and the fibrinolytic factors tissue plasminogen activator (tPA), measured as tPA capacity, and plasminogen activator inhibitor 1 (PAI-1), platelets, fibrinogen, and inflammatory markers were measured in 74 patients with active seropositive RA. Lipid levels, lipoprotein(a), and cardiolipin antibodies were also analyzed. Cardiovascular disease, measured by past cardiovascular events including thrombotic events, was registered in an 8 year followup. RESULTS: Patients with a cardiovascular event during the followup period (n = 26) had significantly higher levels of vWF, PAI-1, erythrocyte sedimentation rate (ESR), and haptoglobin at entry to the study. In a multiple logistic regression model controlling for several conventional cardiovascular risk factors and pharmacological treatment at sampling, PAI-1 and tPA were significantly associated with cardiovascular disease progression. CONCLUSION: The altered levels of vWF, PAI-1, and, in logistic regression, tPA in RA patients with cardiovascular disease progression indicates a status of hypofibrinolysis in these patients. Higher levels of ESR and haptoglobin may reflect the importance of the inflammatory process for the development of cardiovascular disease in RA.

Adult↗

Trace elements and cardiovascular diseases.

Evidence linking marginal intakes of the trace elements, chromium, copper, zinc and selenium, with abnormal lipid metabolism and ultimately cardiovascular diseases is accumulating from both animal and human studies. Chromium supplementation of normal adult men, as well as diabetics, has been reported to increase high density lipoprotein cholesterol and decrease triglycerides and total cholesterol. Subjects with the highest total cholesterol and triglycerides usually respond the most to supplemental chromium. Improvements in lipid metabolism, as well as those in glucose metabolism, appear to be related to improvements in insulin efficiency due likely to increased receptor number. Animal studies also indicate that improvements in serum cholesterol, aortic lipids and plaque formations due to supplemental chromium are associated with decreased circulating insulin. Insufficient dietary copper also leads to elevated lipid levels and impaired heart function. Animal studies indicate an obvious degradation of the heart muscles. Zinc appears to function in cardiovascular diseases primarily via its antagonism with copper. Selenium may also affect cardiovascular diseases since selenium is postulated to be involved in platelet aggregation. These data demonstrate that the trace elements, chromium, copper, and selenium, have beneficial effects on risk factors associated with cardiovascular diseases suggesting that a decreased risk of cardiovascular disease may be achieved by adequate intake of trace elements.

Cardiovascular Diseases↗

A cross-sectional study of the effects of hormon replacement therapy on the cardiovascular disease risk profile in healthy postmenopausal women.

OBJECTIVE: To assess risk factors for cardiovascular disease in healthy postmenopausal women who had been uninterruptedly on menopausal hormone replacement therapy (HRT) for at least 5 years or who had not received any HRT. DESIGN: Cross-sectional study. SETTING: The Royal Free Hospital and The Middlesex Hospital. PATIENT(S): A total of 256 healthy postmenopausal women were analyzed: 73 were taking tibolone, 60 were taking transdermal E(2), 58 were taking conjugated equine estrogens (E), and 65 were not taking any menopausal therapy. INTERVENTION(S): Cardiovascular disease risk factors measurement. MAIN OUTCOME MEASURE(S): Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, lipoprotein(a), insulin, glycated hemoglobin, high sensitivity C-reactive protein, fibrinogen, total antioxidants, and endothelin-1. RESULT(S): The different types of HRT induced disparate changes in the various markers of cardiovascular disease. Significantly higher high sensitivity C-reactive protein concentrations were found in women receiving conjugated equine E and tibolone than in women who were not taking any therapy. Glycated hemoglobin was significantly lower in women receiving transdermal E(2) and tibolone compared to women not on HRT. Women on tibolone had significantly higher systolic blood pressure. CONCLUSION(S): Because high sensitivity C-reactive protein has recently emerged as an important predictor of cardiovascular disease, the higher high sensitivity C-reactive protein levels observed in women on conjugated equine estrogens and on tibolone have potential important clinical implications.

Administration, Cutaneous↗

[Effect of natural factors on the occurrence of cardiovascular diseases].

The effect of natural environmental factors (indexes of solar activity, geomagnetic disturbances, as well as meteorologic parameters: air temperature and humidity, and atmospheric pressure) on the occurrence of cardiovascular diseases in Ukraine as a whole and in Kiev was analyzed. It is shown that, contrary to the stereotype, the yearly dynamics of cardiovascular diseases in 1980-1990 is in opposite phase with the solar activity cycle. Similar results were obtained for the monthly dynamics of cardiovascular diseases in the period from June 1991 to June 1993. The relative influence of five environmental factors (in complex) on the daily dynamics of cardiovascular diseases for the same period was calculated. The role of heliogeophysical factors becomes especially evident if the daily level of cardiovascular diseases within some month of the year is considered. This result may be interesting for medicinal practice and forecasting of cardiovascular diseases.

Cardiovascular Diseases↗

Cardiovascular disease and dyslipidemia in women.

Cardiovascular disease, primarily coronary heart disease (CHD), outnumbers the next 16 causes of death in women combined. However, the long-held belief that heart disease in women has a more benign prognosis than in men has resulted in less aggressive diagnosis and management patterns. Appreciation of the differences between men and women in CHD risk factors and presentation can assist in treatment decisions. Although estrogen replacement offers substantial beneficial effects on lipid levels in postmenopausal women, the first 2 randomized trials of estrogen alone and estrogen plus progestin, the Heart and Estrogen/Progestin Replacement Study and Estrogen Replacement and Atherosclerosis Study, observed no benefit in reducing risk of CHD death and nonfatal myocardial infarction and angiographic progression of CHD, respectively, in women with CHD. Available data show that lipid-lowering therapy reduces women's CHD risk and mortality but also indicate that a considerable proportion of women remains untreated or undertreated. Randomized trials of statins for primary and secondary prevention of coronary heart disease suggest that these agents are at least as effective for lowering coronary disease risk in women as in men. Therefore, statin drugs should be the drug of first choice for women with established CHD. Hypercholesterolemic postmenopausal women who require estrogen for menopausal symptoms may derive further reductions in low-density lipoprotein cholesterol and reductions in trigyceride levels with the addition of a statin drug.

Age Factors↗

Hyperinsulinaemia--a possible risk factor for cardiovascular disease in diabetes mellitus.

Diabetes mellitus is associated with severe and premature cardiovascular disease. The reasons for this have not been identified. It is now apparent that diabetics often have elevated circulating insulin levels compared to non-diabetics. In non-insulin dependent diabetes this is due to the associated obesity while in insulin treated diabetics exogenous insulin is responsible for hyperinsulinaemia between meals and at night. Two reports of high insulin levels in non-insulin dependent diabetics with cardiovascular disease are consistent with clinical and epidemiological studies linking hyperinsulinaemia with coronary, cerebral and peripheral arterial disease in non-diabetics. The arterial wall is an insulin sensitive tissue. Insulin promotes proliferation of arterial smooth muscle cells and enhances lipid synthesis and low density lipoprotein receptor activity. Insulin also promotes experimental atherosclerosis in a number of species. The evidence linking hyperinsulinaemia to the cardiovascular complications and diabetes is suggestive but incomplete and much more information on predictive factors for arterial disease in diabetes is urgently required. Diabetes mellitus is associated with severe and premature cardiovascular disease (reviewed by Stout 1982). Ischaemic heart disease, stroke and peripheral vascular disease are all more common in diabetics, particularly diabetic women. Although there is evidence for the existance of a specific diabetic cardiomyopathy, much of the cardiovascular disease in diabetics is due to atherosclerosis and its complications. Arterial disease in diabetics in distinct from microvascular disease affecting capillaries, and does not differ morphologically or biochemically from atherosclerosis in non-diabetics. The reason for the increased incidence of atherosclerosis in diabetes has not been established. Both non-insulin dependent and insulin dependent diabetes appear to be associated with cardiovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular Diseases↗

The latest from the IVD industry: ever-growing importance of laboratory diagnostics in treating cardiovascular disease.

As cause of death, cardiovascular disease ranks top in mortality statistics. High blood pressure and other risk factors are common. Every year over 300,000 patients are admitted to hospitals in Germany for the treatment of acute myocardial infarction. Two million patients suffer from cardiac insufficiency, although the unrecorded figure is likely to be far higher. Against this background and in the light of the fact that an early, sound diagnosis of these conditions often saves life, tests have been used for about 50 years in the laboratory to detect substances in the blood which are able to identify the cardiovascular risk as well as the acute condition.

Biomarkers↗

Microalbuminuria: a genetic link between diabetes and cardiovascular disease?

Non-insulin-dependent diabetes is associated with a 2-3 fold increased risk of cardiovascular disease. The poor relationship between this risk and either glycaemic control or diabetes duration suggests that some other aspect of the diabetic state, and not hyperglycaemia per se, mediates this risk. This other aspect of diabetes does not comprise alterations in recognized cardiovascular risk factors such as blood pressure or lipids, as the major component of the excess risk is in those diabetics with low levels of the other risk factors. It thus appears that there may be some factors that predispose both to diabetes and to cardiovascular disease. In insulin-dependent diabetics most of the excess risk of cardiovascular disease occurs in subjects with proteinuria, and microalbuminuria or proteinuria in non-insulin-dependent diabetics also substantially increases cardiovascular risk. Although changes in recognized risk factors in diabetics with nephropathy may partly explain these observations, we and others have shown that microalbuminuric non-diabetics also have a markedly increased prevalence of cardiovascular disease and substantially increased cardiovascular mortality. The observations that in insulin-dependent diabetics nephropathy shows family clustering and that these patients have elevated sodium lithium counter-transport rate, a possible genetic marker for the vascular complications of hypertension, have led to the suggestion that microalbuminuria may be a marker of a genetic predisposition to vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Salud para su Corazón: a community-based Latino cardiovascular disease prevention and outreach model.

Cardiovascular disease (CVD) is the leading cause of death for Latinos living in the United States. This population is generally unaware of important lifestyle or behavioral changes that can prevent CVD. The National Heart, Lung, and Blood Institute (NHLBI) designed and implemented Salud para su Corazón (Health for Your Heart), a culturally appropriate, community-based, theory-driven intervention model. NHLBI's goals were: (1) to design an intervention model appropriate to Latino populations; (2) to pilot test the model in a specific community with the objectives of increasing awareness about heart disease, raising knowledge about CVD prevention, and promoting heart-healthy lifestyles; and (3) to disseminate the model and the materials developed to other communities with similar needs. An agency-community partnership, under the leadership of the Community Alliance for Heart Health, guided all stages of the community intervention project. The multimedia bilingual community intervention included television telenovela format public service announcements (PSAs), radio programs, brochures, recipe booklets, charlas, a promotores training manual, and motivational videos. An evaluation survey assessed the impact of the intervention. A pre-post intervention survey was conducted with more than 300 participants, and results showed that the respondents were substantially more aware of risk factors for CVD, and had greatly increased their knowledge of ways to prevent heart disease. Dissemination efforts have resulted in numerous requests by health organizations, universities, and health maintenance organizations (HMOs) for educational materials and communication strategies produced by Salud para su Corazón. In addition, Univision, the largest Spanish-language broadcast television network, is airing the initiative's PSAs. Also, training seminars for promotores are being conducted in different regions of the United States, and several locations are planning to replicate this study.

Adolescent↗

Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults.

CONTEXT: Dietary sodium is positively associated with blood pressure, and ecological and animal studies both have suggested that high dietary sodium intake increases stroke mortality. OBJECTIVE: To examine the risk of cardiovascular disease associated with dietary sodium intake in overweight and nonoverweight persons. DESIGN: Prospective cohort study. SETTING: The first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, conducted in 1982-1984, 1986, 1987, and 1992. PARTICIPANTS: Of those aged 25 to 74 years when the survey was conducted in 1971 -1975 (14407 participants), a total of 2688 overweight and 6797 nonoverweight persons were included in the analysis. MAIN OUTCOME MEASURES: Dietary sodium and energy intake were estimated at baseline using a single 24-hour dietary recall method. Incidence and mortality data for cardiovascular disease were obtained from medical records and death certificates. RESULTS: For overweight and nonoverweight persons, over an average of 19 years of follow-up, the total number of documented cases were as follows: 680 stroke events (210 fatal), 1727 coronary heart disease events (614 fatal), 895 cardiovascular disease deaths, and 2486 deaths from all causes. Among overweight persons with an average energy intake of 7452 kJ, a 100 mmol higher sodium intake was associated with a 32% increase (relative risk [RR], 1.32; 95% confidence interval [CI], 1.07-1.64; P = .01) in stroke incidence, 89% increase (RR, 1.89; 95% CI, 1.31-2.74; P<.001) in stroke mortality, 44% increase (RR, 1.44; 95% CI, 1.14-1.81; P = .002) in coronary heart disease mortality, 61% increase (RR, 1.61; 95% CI, 1.32-1.96; P<.001) in cardiovascular disease mortality, and 39% increase (RR, 1.39; 95% CI, 1.23-1.58; P<.001) in mortality from all causes. Dietary sodium intake was not significantly associated with cardiovascular disease risk in nonoverweight persons. CONCLUSIONS: Our analysis indicates that high sodium intake is strongly and independently associated with an increased risk of cardiovascular disease and all-cause mortality in overweight persons.

Adult↗

Primary prevention of cardiovascular disease: managing hypertension and hyperlipidaemia.

Cardiovascular medicine has a sound evidence base upon which health professionals can base their interventions to modify risk among the British public. For primary prevention of cardiovascular disease, however, while there is considerable evidence on what to do, data are limited on how the evidence should be implemented in practice. The challenge will be to learn by experience which interventions directed at reducing blood pressure and lipids levels work best in different settings. There is a need to structure care to identify individuals who are at risk. Current targets are explicit and achievable for both hypertension and lipids. Effective treatment is likely to require multiple drug treatment.

Attitude to Health↗

Cardiovascular disease in early stages of chronic kidney disease in a Chinese population.

Cardiovascular disease (CVD) is one of the most serious complications of kidney disease, yet studies of CVD in early stage of chronic kidney disease (CKD) in Asian patients are very limited. Therefore, this study determined the prevalence and the spectrum of CVD in individuals with early-stage CKD and compared them with data of individuals without CKD. Compared with individuals with estimated GFR (eGFR) >90 ml/min per 1.73 m2, the prevalence of myocardial infarction, stroke, and total CVD of individuals with eGFR 60 to 89 ml/min per 1.73 m2 was increased by 91.4, 71.7, and 67.6%, respectively. For individuals with eGFR 30 to 59 ml/min per 1.73 m2, the percentage was 105.2, 289.1, and 200.7%, respectively. For each eGFR category, stroke was more prevalent than myocardial infarction. Compared with individuals with eGFR >90 ml/min per 1.73 m2, participants with eGFR 60 to 89 and 30 to 59 ml/min per 1.73 m2 tended to have more cardiovascular risk factors, and there were strong unadjusted and adjusted associations between CVD with different stages of eGFR (eGFR >90 ml/min per 1.73 m2 as reference). This is the first report on the prevalence and the spectrum of CVD in early stages of CKD in a community-based Chinese population. The spectrum of CVD in this Chinese population is different from reports of Western countries. Individuals with subtle decreased renal function seem much more likely to have multiple cardiovascular risk factors and have higher prevalence of CVD than those without CKD.

Adult↗

Comparative assessment of lipid effects of endocrine therapy for breast cancer: implications for cardiovascular disease prevention in postmenopausal women.

Cardiovascular disease (CVD) is the leading cause of death in the developed world for both men and women. Women experience significant alterations in lipid profiles during the years following menopause, including a reduction in plasma high-density lipoprotein cholesterol and an elevation of plasma low-density lipoprotein cholesterol, and are at an increased risk of CVD. These changes are due in part to the reduction in estrogen production following the onset of the menopause. Therefore, agents that have anti-estrogenic effects, such as most endocrine therapies for breast cancer, may increase the risk of CVD. Tamoxifen, historically the standard endocrine therapy, has an overall beneficial effect on lipid profiles. However, long-term data from clinical trials have failed to demonstrate a cardioprotective effect and patients treated with tamoxifen did not experience fewer cardiovascular events compared with those receiving placebo. Indeed, a number of studies have shown that tamoxifen may have a detrimental effect, with a significantly increased risk of venous thromboembolic events, pulmonary embolism and stroke. The third-generation aromatase inhibitors (AIs) have demonstrated an improvement in efficacy and tolerability over previous treatments. Since they have a different mechanism of action to tamoxifen, they are not anticipated to exert the same impact on lipid profiles. Clinical trials with anastrozole demonstrated no clinically relevant impact on lipid profiles in postmenopausal patients with advanced breast cancer. However, as lipid profiles are surrogate endpoints, the most appropriate endpoint is the incidence of cardiovascular events in long-term studies. This is of particular relevance in the treatment of early breast cancer, where endocrine agents may be used in the adjuvant setting for periods of 5 years or more. Long-term adjuvant anastrozole treatment resulted in significantly fewer thromboembolic and cerebrovascular events and a similar incidence of ischemic cardiovascular events compared with tamoxifen. The effects of the other AIs on lipid levels are variable, and any correlation with cardiovascular events is currently unknown.

Anastrozole↗