Genetic testing and genetic counseling in cardiovascular genetic medicine: overview and preliminary recommendations

In this emerging era of cardiovascular genetic medicine, increasing responsibility will be placed on cardiovascular practitioners to be aware of the latest clinical genetic testing methods and the knowledge base needed to interpret genetic test results. Some cardiovascular specialists will develop the expertise within the field to order genetic testing and interpret results, while other practitioners will refer patients to centers of excellence in cardiovascular genetic medicine. A previous article in the Cardiovascular Genetic Medicine: Clinical Perspectives and Future Applications series(1) highlighted an increasing recognition of the cardiomyopathies (hypertrophic [HCM], dilated [DCM], arrhythmogenic right ventricular dysplasia [ARVD]) and channelopathies (long QT syndrome [LQTS] and others) as genetic diseases, and focused on the importance of a targeted family history as a critical part of patient evaluation. The goal of this article, second in the series, is to provide a general framework for understanding the principles of genetic testing and genetic counseling. We review the growing number of genetic tests currently available to cardiac specialists, the selection of an appropriate test, and the numerous genetic counseling issues raised by the testing process. We also provide our preliminary recommendations for genetic testing in cardiovascular genetic medicine.     

Family history of heart attack as an independent predictor of death due to cardiovascular disease

Although a family history of ischemic heart disease is a well-accepted risk factor for cardiovascular disease, only three prospective studies--all in men--have examined the predictive strength of a positive family history after adjusting for other heart disease risk factors. The present analysis is based on a 9 year follow-up of 4014 men and women from 40 to 79 years old who resided in Rancho Bernardo, CA, and who reported no known cardiovascular disease in response to a standardized interview. At baseline 38% of this group reported a family history of a heart attack in a parent, sibling, or child; 15% of those with a positive family history in a first-degree relative indicated that the heart attack had occurred before the relative was 50 years old. Younger men (less than 60 years) with a positive family history at any age had significantly higher mean blood pressures and total plasma cholesterol levels; older men were more likely to have diabetes mellitus. Younger women with a positive family heart attack to subsequent cardiovascular death was determined by the Cox model after adjusting for age, systolic blood pressure, total plasma cholesterol level, obesity, cigarette smoking, personal history of diabetes, and estrogen use (in women). In men, but not in women, a positive family history of heart attack was independently predictive of death from all causes and from cardiovascular and ischemic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Usefulness of cardiovascular family history data for population-based preventive medicine and medical research (the Health Family Tree Study and the NHLBI Family Heart Study)

Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family Tree Study, and 1,442 families in the NHLBI Family Heart Study in Massachusetts, Minnesota, North Carolina, and Utah. Utah families with a positive family history of CHD (FRS > or =0.5) represented only 14% of the general population but accounted for 72% of persons with early CHD (men before age 55 years, women before age 65 years) and 48% of CHD at all ages. For strokes, 11% of families with FRS > or =0.5 accounted for 86% of early strokes (<75 years) and 68% of all strokes. Analyses of >5,000 families sampled each year in Utah for 14 years demonstrated a gradual decrease in the frequency of a strong positive family history of CHD (-26%/decade) and stroke (-15%/decade) that paralleled a decrease in incidence rates (r = 0.86, p <0.001 for CHD; r = 0.66, p <0.01 for stroke). Because of the collaboration of schools, health departments, and medical schools, the Health Family Tree Study proved to be a highly cost-efficient method for identifying 17,064 CHD-prone families and 13,106 stroke-prone families (at a cost of about $27 per high-risk family) in whom well-established preventive measures can be encouraged. We conclude that most early cardiovascular events in a population occur in families with a positive family history of cardiovascular disease. Family history collection is a validated and relatively inexpensive tool for family-based preventive medicine and medical research.     

Family history of essential hypertension versus obesity as risk factors for hypertension in adolescents

Family history of hypertension and obesity are both risk factors for hypertension. Hypertension and obesity share several physiopathologic abnormalities and are frequently associated. However, not all obese people are hypertensive. Renal handling of sodium has been proposed as a physiopathogenic mechanism of essential hypertension and obesity. This study was conducted in obese adolescents to evaluate the role of a family history of hypertension versus obesity in the renal handling of sodium. Fractional excretion of lithium (FELi) and uric acid (FEUA) were measured in 46 obese adolescent offspring of hypertensive parents (OH: body mass index [BMI], 29.5 +/- 0.6 kg/m2, age 14.2 +/- 0.3 years, 22 males); eight obese offspring of normotensive parents (ON: BMI, 30.7 +/- 1.7 kg/m2, 14.8 +/- 0.8 years, four males), and in 34 lean adolescent offspring of hypertensive parents (LH: BMI, 20.5 +/- 0.5 kg/m2, 14.3 +/- 0.3 years, 24 males). FELi in OH was 16.5% +/- 1.3%, in ON it was 22.4% +/- 2.3%, and in LH it was 14.4% +/- 1.2% (P < .05). FEUA in OH was 8.5% +/- 0.8%, in ON it was 14.8% +/- 3.6%, and in LH it was 7.9% +/- 0.8% (P < .01). Plasma renin activity (PRA) and aldosterone (PA) were measured in OH and LH; PRA was 5.3 +/- 0.4 and 4.5 +/- 0.4 ng/mL/h, respectively (P = NS), and PA was 366 +/- 36 and 242 +/- 32 pg/mL, respectively (P < .05). In summary, adolescents with a family history of hypertension, regardless of their body mass, have a diminished FELi and FEUA. Obese adolescents also have higher plasma levels of aldosterone than lean ones. In conclusion, the family history of hypertension would be related to the increased renal proximal sodium reabsorption whereas obesity would be related to increased distal sodium reabsorption mechanisms, such as aldosterone. Both mechanisms could explain the higher prevalence of hypertension in obese offspring of hypertensive parents.     

Family history of cardiovascular disease does not predict risk-reducing behavior.

BACKGROUND: Family history is one of the main risk factors for cardiovascular disease, especially in the younger population. These individuals, being closely related to young symptomatic patients, are anticipated to have a high rate of risk factors but also to control them aggressively. The aim of the study was to evaluate the association between family history of cardiovascular disease and risk factors that control as well as reduce risk-reducing behavior among young, healthy adults. DESIGN AND METHODS: Demographic, clinical and lifestyle parameters of career service personnel of the Israeli Defense Forces, who were checked at the staff periodic examination center, were evaluated. Behavioral and clinical parameters of participants, with and without cardiovascular family history, were compared. RESULTS: The study cohort comprised 41,099 patients (36,236 men and 4863 women). Of those, 3802 men and 628 women with a family history of cardiovascular disease were identified. Male individuals had a higher rate of treatable risk factors like, obesity (P<0.0005), high blood pressure (P<0.0005), high plasma glucose (P<0.0005) and dyslipidemia (P<0.0005) than individuals without a family history. Among the women, the rate of these risk factors was higher than in the control groups but was statistically significant only for obesity, high blood pressure and high glucose levels. Risk-reducing behavior like regular physical activity and nonsmoking status in both the sexes did not differ between the groups. CONCLUSION: Members of the young population with a family history of cardiovascular disease is easily identified but remains largely uncontrolled. Special attention and continued education are required to modify their behavioral and medical parameters.     

Family history as an independent risk factor for coronary artery disease

The risk of family history of ischemic heart disease independent of other well described risk factors has remained difficult to quantitate. Significant coronary artery disease was determined by coronary arteriography to be present in 223 patients and absent in 57 control subjects. Age, sex, blood pressure, serum cholesterol, cigarette smoking and the presence of diabetes and left ventricular hypertrophy on the electrocardiogram were tabulated for each patient and the data used to assign a risk score based on the American Heart Association multivariate model. Subjects were stratified and matched according to risk score to estimate risk of family history independent of familial aggregation of these seven other risk factors. Angina, myocardial infarction, cardiac death and any ischemic heart disease were ascertained in 1,319 first degree relatives. Odds ratios for overall, stratified and matched comparisons of these end points in relatives of patients and control subjects ranged between 2.0 and 3.9 (p less than 0.01 for all comparisons), indicating a higher frequency of all ischemic heart disease end points in relatives of patients with documented coronary artery disease. Life table comparison of patients at lowest risk with those at higher risk showed significantly greater cumulative frequency and earlier age of onset of all ischemic heart disease end points in relatives of low risk patients. These observations indicate that some of the risk associated with family history is independent of familial aggregation of other known risk factors and suggest that the independent effects of family history may be most important in individuals who otherwise are at low risk.     

处方回顾性评估:衡量结核病防治服务质量的一个基本方法

遏制结核病策略1和结核病关怀国际标准2的第一个组成部分即为:使用推荐的抗结核药品剂型和剂量,组成标准治疗方案,治愈结核病患者,使其恢复健康和劳动能力,并减少结核分枝杆菌的传播,从而预防耐药结核病的发生和传播。在这一期的国际结核病与肺部疾病杂志上,江     

W. Proctor Harvey: a master clinician-teacher's influence on the history of cardiovascular medicine

Medicine has become driven by research and technology, both of which have yielded indisputable benefits. Yet we are now so dependent upon such advancements that many practitioners have lost the basic clinical skills that enable bedside diagnosis. In the 2nd half of the 20th century, W. Proctor Harvey helped to keep alive the classic art of medicine.     

Family history of cardiovascular events and endothelial dysfunction in children with familial hypercholesterolemia

BACKGROUND: Aortic valve calcification without obstruction (AVC) is common in the elderly and is associated with increased cardiovascular mortality and morbidity. We hypothesized that AVC detected by transthoracic echocardiography (TTE) is a marker for significant coronary artery disease in patients undergoing coronary angiography. METHODS: The study group included 388 patients with AVC (259 males, 129 females; mean age 72.2+/-9 years) who underwent coronary angiography for various indications. Data were compared with 320, age- and sex-matched patients without AVC who underwent coronary angiography for the same indications. AVC was detected in TTE as focal areas of increased echogenicity and thickening of the aortic-valve leaflets without restriction in motion. Significant obstructive coronary artery disease was defined as either a > or = 70% reduction of the internal diameter of the left anterior descending, right coronary, or left circumflex artery distribution or a > or = 50% reduction of the internal diameter of the left main coronary artery. Risk factors for atherosclerosis including hypertension, smoking, hypercholesterolemia and diabetes were also investigated. RESULTS: Compared with control group, the AVC group had a higher prevalence of significant coronary artery disease (90 vs. 85%, P=0.019), and a trend for lower frequency of coronary arteries without obstruction (6 vs. 9%, P=0.l1); a trend was also noted for 3-vessel disease (38 vs. 33%, P=0.14). Multivariate analysis identified age (P=0.000l), sex (P=0.000l), hypercholesterolemia (P=0.005) and AVC (P=0.02) as independent predictors for significant coronary artery disease. CONCLUSIONS: There is a significant association between AVC and significant coronary artery disease in patients undergoing coronary angiography. Thus AVC can serve as a window to atherosclerosis of the coronary arteries. These results reinforce a previous observation regarding association between AVC and increased risk of cardiovascular morbidity.