Gene/Protein Disease Symptom Drug Enzyme Compound
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Mild hyperhomocysteinemia has been considered a cardiovascular risk factor. However, recent prospective studies have not demonstrated that hyperhomocysteinemia or the underlying genetic defect on methylentetrahydrofolate reductase is associated with a higher risk of coronary or peripheral artery disease. We compared serum homocysteine, folate, and vitamin B(12) levels of patients with coronary and peripheral vascular disease with those of age- and sex-matched healthy individuals. Subjects taking multivitamins, with diabetes mellitus, or serum creatinine levels over 1.5 mg/dL were excluded from the study. Homocysteine was measured by fluorimetric high-performance liquid chromatography. Serum folate and vitamin B(12) levels were measured by an ion-capture method. We studied 32 patients with peripheral vascular disease (10 female), aged 69.6 +/- 11 y, 24 age- and sex-matched control subjects, 52 patients with coronary artery disease (7 female), aged 59.5 +/- 10.4 y, and 42 age- and sex-matched control subjects. Serum homocysteine levels were 11.7 +/- 7.4 and 9.3 +/- 4.5 micromol/L in vascular patients and in the control counterparts, respectively (not significant). The levels for coronary patients and the control counterparts were 9.0 +/- 3.9 and 8.6 +/- 3.6 micromol/L, respectively (not significant). Folate levels were 4.48 +/- 2.42 and 7.14 +/- 4.04 ng/mL in vascular patients and control subjects, respectively (P < 0.02); the levels in coronary patients and control counterparts were 5.15 +/- 1.9 and 6.59 +/- 2.49 ng/mL, respectively (P < 0.01). No differences in vitamin B(12) or tocopherol levels were observed between patients and control subjects. There were no differences in homocysteine levels, but lower serum folate levels were observed when comparing patients with atherosclerotic vascular disease and healthy control subjects.
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PMID:Low serum folate but normal homocysteine levels in patients with atherosclerotic vascular disease and matched healthy controls. 1086 99

Hypertension is one of the main risk factors for cerebrovascular disease (stroke), coronary artery disease (acute myocardial infarction), congestive heart failure (both systolic and diastolic dysfunction), and renal dysfunction. The risk is related to blood pressure level and to the presence of target organ damage. Together with hypertension, other cardiovascular risk factors, such as hyperlipidemia and/or diabetes, also contribute to the chain of events leading to atherosclerosis, vascular complications and death. Three-quarters of middle-aged, urban population show at least one cardiovascular risk factor and 91.3% of all hypertensives show at least one cardiovascular risk factor in addition to hypertension itself. In most populations, the risk of cardiovascular disease rises steeply with age. This powerful effect of age on disease risk has important consequences for the risk of cardiovascular disease related to blood pressure and other risk factors. At most ages the risk for cardiovascular diseases is higher in men than in women, although this difference declines with increasing age and is greater for coronary heart disease than for stroke; in the United States from age 34 to 74 the risk of death from coronary heart disease is 2- to 3-fold greater in men; the risk of death from stroke is 30% higher in men than in women; after age 75 the risk of death from stroke and from coronary heart disease is similar in men and women. Postmenopausal women share the same risk with men for cardiovascular disease. For many years the study and treatment of hypertension has been largely directed toward diastolic blood pressure; the importance of elevated systolic blood pressure in the management of cardiovascular disease is being largely underrecognized. Convincing evidence is presently available indicating that elevated systolic blood pressure is even a stronger predictor than diastolic blood pressure for progression of cardiovascular disease and adverse outcomes. The clinical and laboratory evaluation and drug treatment of the hypertension is related to age. The elderly benefit from treatment of elevated systolic blood pressure as much or even more than middle-aged hypertensive subjects. Two large clinical trials on treatment of isolated systolic hypertension, the Systolic Hypertension in the Elderly Program (SHEP) and the Systolic Hypertension in Europe Study (Syst-Eur), have demonstrated that antihypertensive drug therapy in elderly patients with isolated systolic hypertension effectively reduces the risk of stroke and other major cardiovascular events.
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PMID:[Hypertension as a function of age]. 1090 25

Definitive studies of the effectiveness of screening for type 2 diabetes are currently not available. RCTs would be the best means to assess effectiveness, but several barriers prevent these studies from being conducted. Prospective observational studies may characterize some of the benefits of screening by creating screened and unscreened groups for comparison. The availability of better data systems and health services research techniques will facilitate such comparisons. Unfortunately, the interpretation of the results of such studies is extremely problematic. Several screening tests have been evaluated. Risk assessment questionnaires have generally performed poorly as stand-alone tests. Screening with biochemical tests performs better. Venous and capillary glucose measurements may perform more favorably than urinary glucose or HbA(1c) measurements, and measuring postprandial glucose levels may have advantages over measuring fasting levels. However, performance of all screening tests is dependent on the cutoff point selected. Unfortunately, there are no well-defined and validated cutoff points to define positive tests. A two-stage screening test strategy may assist with a more efficient use of resources, although such approaches have not been rigorously tested. The optimal interval for screening is unknown. Even though periodic, targeted, and opportunistic screening within the existing health care system seems to offer the greatest yield and likelihood of appropriate follow-up and treatment, much of the reported experience with screening appears to be episodic poorly targeted community screening outside of the existing health care system. Statistical models have helped to answer some of the key questions concerning areas in which there is lack of empirical data. Current models need to be refined with new clinical and epidemiological information, such as the UKPDS results (200). In addition, future models need to include better information on the natural history of the preclinical phase of diabetes. Data from ongoing clinical trials of screening and treatment of impaired glucose tolerance, such as the Diabetes Prevention Program, may eventually offer more direct evidence for early detection and treatment of asymptomatic hyperglycemia (201). It will be important to use comprehensive cardiovascular disease modules that assess the conjoint influence of glucose and cardiovascular risk factor reduction, information on QOL, and refined economic evaluations using common outcome measures (cost per life-year or QALY gained) (11,178,202-204). Such studies should consider all of the costs associated with a comprehensive screening program, including, at a minimum, the direct costs of screening, diagnostic testing, and care for patients with diabetes detected through screening. Finally, combinations of screening tests and different screening intervals should be evaluated within economic studies to allow selection of the optimal approach within the financial and resource limitations of the health care system.
Diabetes Care 2000 Oct
PMID:Screening for type 2 diabetes. 1102 53

Clinical studies evaluating the benefits of angiotensin-converting-enzyme (ACE) inhibitor therapy in patients likely to develop renal disease are reviewed. Patients with diabetes or hypertension are at increased risk for development of renal disease. In patients with diabetic nephropathy, captopril therapy was associated with a 50% reduction in the risk of death, dialysis, and transplantation and a significantly smaller increase in serum creatinine compared with placebo. Therapy with enalapril or lisinopril has been shown to limit the progression of renal disease in normoalbuminuric patients with diabetes. Long-term therapy with enalapril (up to seven years) has demonstrated the ability to preserve renal function in patients with diabetes and microalbuminuria. Over 4.5 years, patients with diabetes and at least one other cardiovascular risk factor had significant reductions in the risk of overt nephropathy with ramipril therapy compared with placebo. In addition, ramipril is associated with preservation of renal function in patients with nondiabetic nephropathy. Evidence suggesting a dissociation of the renal hemodynamic and antiproteinuric effects of ACE inhibition is presented. These positive effects of ACE inhibition cannot be explained by reductions in blood pressure alone. ACE inhibitors have renoprotective properties beyond systemic blood pressure reduction.
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PMID:Role of angiotensin-converting-enzyme inhibition in patients with renal disease. 1103 18

Many important developments recently have been made in the treatment and prevention of coronary artery disease (CAD) in postmenopausal women. Substantial evidence supports focusing on comprehensive risk factor modification based on the "ABCs" of CAD management from the American College of Cardiology, the American Heart Association, and the American College of Physicians-American Society of Internal Medicine guidelines on chronic stable angina. This approach emphasizes cardiovascular risk factor interventions that include antiplatelet agents, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, cholesterol-lowering medications, diabetes control, and counseling on diet and exercise. Despite the expanding available literature, many questions on CAD in postmenopausal women remain unanswered and await the publication of ongoing and future research. The unexpected findings from the HERS (Heart and Estrogen/progestin Replacement Study) failed to show a benefit of hormone replacement therapy (HRT) in reducing the risk of subsequent events in postmenopausal women with CAD, and instead reported an early increase in CAD events. Based on the data available so far, we advise against starting HRT in postmenopausal women with a recent coronary event for the sole purpose of CAD prevention. For women with acute coronary syndromes, prompt angiography and revascularization should be considered.
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PMID:Coronary Artery Disease in Postmenopausal Women. 1113 91

Cardiovascular disease is the major cause of death in patients with end-stage renal disease (ESRD). ESRD patients are almost invariably hypertensive. They all have acquired combined hyperlipidemia and increased Lp(a), hyperhomocysteinemia, decreased physical activity, psychosocial stress, insulin resistance, procoagulant factors, left ventricular hypertrophy, and increased oxidative stress. Diabetes mellitus, a major risk factor for both cardiovascular disease and ESRD, has become the commonest cause of ESRD. If ESRD patients choose to smoke, the additive risk is profound. Moreover, ESRD patients are becoming older and are often menopausal if female. Finally, ESRD patients have a dramatic tendency for vascular and cardiac calcification, probably related to hyperphosphatemia and hyperparathyroidism. Cardiovascular disease is also a major risk in patients with decreased renal function of nearly any degree. Data from the HDFP study showed that patients with a serum creatinine concentration > 1.5 mg/dl had a profoundly higher risk of cardiovascular disease than patients with creatinine values below this value. These data were recently corroborated in the HOPE study. Microalbuminuria (MAU), with or without diabetes mellitus, indicates increased cardiovascular disease risk even without decreases in glomerular filtration rate. We found earlier that nondiabetic hypertensive patients with MAU had much higher rates of myocardial infarction, stroke, and peripheral vascular disease, than similar hypertensive patients without MAU. In conclusion, the presence of decreased renal function or MAU is a major cardiovascular risk factor. ESRD can be regarded as a catastrophic risk factor. Prophylactic measures known to be effective in reducing the risk from cardiovascular disease are grossly underused. Unfortunately, they are less effective in patients with renal disease, and new strategies are needed.
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PMID:Renal disease as a risk factor for cardiovascular disease. 1119 57

Several single-nucleotide polymorphisms (SNPs) of platelet receptors have been implicated to be associated with an increased risk of arterial thrombosis; this review focuses on the mechanisms and the clinical significance of two specific single-nucleotide polymorphisms, ie the GP IIIa L33P (=PlA1/2) and the GP Ia 807 C/T. Whereas the mechanism of P1A2 is thought to result from 'gain of receptor function' (and there is still considerable controversy on this subject), the collagen receptor SNP is associated with an increased number of receptors on the platelet surface, thus offering a plausible explanation for the observed increased interaction with collagen and the increased risk of thrombotic events reported in some studies but not in others. Overall, the presently available (controversial) data do still not allow the conclusion that the GPIIIa polymorphism alone represents a cardiovascular risk factor in the general population. A number of mechanisms and a series of studies suggest, however, that it may be a risk factor in certain subgroups of patients or in a number of clinical situations. The GPIa SNP discussed seems to be a mild risk factor that is particularly important in synergism with known risk factors, such as smoking, hypertension, diabetes or proteinuria, etc, which may enhance its contribution to the overall cardiovascular risk.
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PMID:Genetics of platelet receptor single-nucleotide polymorphisms: clinical implications in thrombosis. 1120 74

Smoking is a major cardiovascular risk factor and cause of death. Diabetes mellitus is also associated with an increased mortality and morbidity. Evidence concerning whether smoking increases the incidence of diabetes remains conflicting. Glycaemic status and smoking habits were analysed in 3718 Chinese subjects in order to assess the possible association between smoking and risk of diabetes in the Chinese population. The World Health Organisation 1998 criteria were used for the diagnosis of glucose intolerance. Smoking was defined as current cigarette smoking or ex-smoking without regard to daily consumption. The smoking habits of the studied subjects were correlated with glycaemic status. There were 3003 (80.8%) women and 715 (19.2%) men. The mean age (SD) was 38.4 (12.8) years (median 35.0, range 12-88 years). Of the 3718 subjects, 786 (21.1%) had diabetes, 708 (19.1%) had impaired glucose tolerance, and 2224 (59.8%) had normal results. Of the 3003 women, only 87 (2.9%) were smokers. The female smokers were younger, heavier, and had higher alcohol consumption than non-smokers. The prevalence of diabetes was similar between female smokers and non-smokers after adjustment for age, body mass index, family history of diabetes, and alcohol. Of the 715 men, 175 (24.5%) were smokers. The male smokers were younger, had lower blood pressure, and higher alcohol consumption. After adjustment for age, body mass index, family history of diabetes and alcohol, the male smokers had lower blood pressure, higher one hour plasma glucose, and more diabetes. Using logistic regression analysis (stepwise forward) with age, body mass index, alcohol, smoking, and family history of diabetes as independent variables to predict the risk of having diabetes, age and body mass index are independently associated with diabetes in both men and women. In addition, smoking is independently associated with the risk of diabetes in men, the odds ratio (95% confidence interval, CI) being 1.705 (1.106 to 2.630). Family history of diabetes is independently associated with the risk of diabetes in women, and the odds ratio (95% CI) is 1.643 (1.314, to 2.053). In conclusion, it was found that smoking is independently associated with diabetes after adjustment for age, body mass index, alcohol, and family history of diabetes in Hong Kong Chinese men, the odds ratio being 1.7. The prevalence of smoking in Hong Kong Chinese women is low and its association with diabetes is inconclusive.
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PMID:Smoking and diabetes in Chinese men. 1150 4

An in-depth cardiovascular risk factor assessment was carried out in a sample of 205 Korean American elderly in Maryland, consisting of 75 males and 130 females aged 60 to 89 years (mean age = 69.9 +/- 6.5 years). Six risk factors were assessed in each participant: high blood pressure, current smoking, high blood cholesterol, overweight, sedentary lifestyle, and diabetes. The findings of this cross-sectional study suggested that high blood pressure was the leading cardiovascular disease risk factor among Korean American elderly (71%), followed by high blood cholesterol (53%), overweight (43%), sedentary life style (24%), diabetes (18%), and smoking (7%). Two thirds of the sample had multiple cardiovascular disease risk factors. The pattern of prevalence and risk factors that was observed was consistent with the distribution of multiple risk factors in that the combination of high blood pressure, high blood cholesterol, and overweight was most common in Korean American elderly (62%). These findings indicate that culturally relevant and salient strategies are needed to reduce multiple risk factors in this population.
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PMID:Cardiovascular disease risk factors in Korean American elderly. 1129 31

Associations between sleep-disordered breathing and cardiovascular disease (CVD) may be mediated by higher cardiovascular risk factor levels in those with sleep-disordered breathing. The authors examined these relations in the Sleep Heart Health Study, a multiethnic cohort of 6,440 men and women over age 40 years conducted from October 1995 to February 1998 and characterized by home polysomnography. In 4,991 participants who were free of self-reported CVD at the time of the sleep study, moderate levels of sleep-disordered breathing were common, with a median Respiratory Disturbance Index (RDI) of 4.0 (interquartile range, 1.25-10.7). The level of RDI was associated cross-sectionally with age, body mass index, waist-to-hip ratio, hypertension, diabetes, and lipid levels. These relations were more pronounced in those under age 65 years than in those over age 65. Women under age 65 years with RDI in the higher quartiles were more obese than men with similar RDI. Although the pattern of associations was consistent with greater obesity in those with higher RDI, higher body mass index did not explain all of these associations. If sleep-disordered breathing is shown in future follow-up to increase the risk for incident CVD events, part of the risk is likely to be due to the higher cardiovascular risk factors in those with higher RDI.
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PMID:Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study. 1143 66


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