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PubMed1992

Biological complexity and strategies for finding DNA variations responsible for inter-individual variation in risk of a common chronic disease, coronary artery disease.

Most common chronic diseases of humans aggregate, but do not segregate, in families. The segregation-linkage research paradigm has not provided great insights into their genetic etiology. In this paper, using coronary artery disease as an example, we discuss hierarchical organization, coherence, emergent properties and dynamism as features that characterize the complexity of genotype-phenotype relationships. We summarize a research strategy for evaluating the contribution of genetic and environmental factors to the prediction of inter-individual variation in risk of disease. We then review a statistical strategy that employs cladistic theory to identify individuals carrying mutant DNA sequences responsible for an observed association between marker variation in a gene and inter-individual variation in biological traits that determine risk of a common multifactorial disease. Finding these DNA sequences is a necessary step in our search for an understanding of the nature of the mapping of genetic variation into variation in risk of a disease like coronary artery disease.

Coronary Disease↗
PubMed1999

Treatment of moderate mitral regurgitation and coronary disease by coronary bypass alone: late results.

BACKGROUND: In cases of moderate mitral regurgitation and coronary artery disease operative strategy continues to be debated between coronary artery bypass grafting alone and concomitant valve replacement or repair. We previously reported on 58 patients with moderate mitral regurgitation who had coronary artery bypass grafting between 1977 and 1983. We present the late results for this original cohort (test group), and a matched control group of coronary artery bypass grafting patients without mitral regurgitation (n = 58). METHODS AND RESULTS: In the original cohort, the hospital mortality rate was 3.4% (2 of 58), and 80.4% (45 of 56) of hospital survivors were alive at the time of initial follow-up (mean, 4.3+/-2.3 years). Hospital mortality in the control group was 6.9% (4 of 58 patients). Follow-up was 98.2% (108 of 110 patients) complete, with a mean follow-up time of 10.3+/-5.5 years. Kaplan-Meier curves for hospital survivors showed similar 5- and 10-year survival rates between the two groups (p = 0.59). On multivariate analysis, age 65 years or more, congestive heart failure class III or IV, and pulmonary capillary wedge pressure more than 17 mm Hg were significant (p < 0.05) independent predictors of diminished survival in the test group. CONCLUSIONS: Patients with moderate mitral regurgitation and coronary artery disease treated solely with coronary artery bypass grafting had acceptable early and late results. Moderate mitral regurgitation at the time of revascularization does not always warrant operative correction.

Aged↗
PubMed1989

[Complex angioplasty. (I). Single dilatation versus multiple dilatation in patients with multi-vessel coronary disease].

Coronary angioplasty was successfully performed in 658/752 multivessel disease patients. One lesion was attempted in 338 patients (45%); two or more in 414 patients (55%). Complications occurred in 39 patients (5.2%): 19 (2.5%) had a transmural infarction, 26 (3.5%) urgent surgery, and 14 (1.9%) died. Recurrence occurred in 233/658 (35%) patients with 162/171 (94.7%) having a successful second angioplasty. Clinical improvement (follow-up: 31 months) remained in 81% of successful patients. Survival was not affected by the number of dilations performed but was adversely affected by the presence of prior surgery and ventricular dysfunction. Angioplasty can be an effective treatment without the need to dilate all vessels.

Aged↗
PubMed2002

Prevention of cardiovascular diseases. Coronary artery disease, congestive heart failure, and stroke.

Cardiovascular disease leads to significant morbidity and mortality in the older population. Results of risk reduction can be dramatic in terms of patient survival and quality of life. This article reviews evidence for cardiovascular risk factors and disease prevention in older adults. Interventions which reduce morbidity and mortality from coronary artery disease, heart failure, and cerebrovascular disease in the elderly population are examined. Attention is given to the role of cardiovascular disease in older women and in minorities, subsets not well-represented in many studies.

Aged↗
PubMed1985

[Surgical treatment of heart valve diseases and coronary diseases in the elderly].

The results of the operative treatment of valvular and coronary heart disease in large groups of elderly patients demonstrate that age per se is no contraindication for cardiac surgery. Age holds only the sixth place in the ranking list of risk factors, at least for coronary revascularization. One has to be aware that the operative risk in patients well over 60 years of age is somewhat higher than in younger individuals. However, there is no clearly identifiable age-related measure for indication or contraindication in the particular case. Surgery should be considered in an elderly patient if he or she had been leading a normal active life before the onset of limiting symptoms caused by the underlying valvular or coronary heart disease. These patients should have a strong motivation to improve their lifestyle postoperatively. Severe additional disease should be considered as a potential reason for renunciation.

Age Factors↗
PubMed1987

The association of body fat distribution with hypertension, hypertensive heart disease, coronary heart disease, diabetes and cardiovascular risk factors in men and women aged 18-79 years.

To confirm the reported association of body fat distribution with cardiovascular disease, diabetes, blood pressure and serum cholesterol, data from the 1960-62 Health Examination Survey were analyzed. In this sample drawn from the noninstitutionalized population of the United States aged 18-79, mean values of two indices of upper versus lower body fat distribution increased steadily with age. Men had higher values than women, and black women had higher values than white women. Higher values of the indices were significantly associated with higher blood pressure, post-load serum glucose and greater prevalence of definite hypertension and definite hypertensive heart disease independent of multiple confounders. Associations with higher serum cholesterol and definite coronary heart disease prevalence were independent of overall ponderosity but not of age and multiple other confounders. Greater abdominal relative to lower body fat deposits were independently associated with increased cardiovascular risk in men and women, blacks and whites.

Adipose Tissue↗
PubMed1995

In patients with hypertensive left ventricular hypertrophy and coronary heart disease, coronary flow reserve is similarly impaired.

Coronary blood flow reserve (CFR) was assessed by transesophageal Doppler echocardiography in normal subjects (group A, n = 20), hypertensive non-left ventricular hypertrophy (non-LVH) patients (group B, n = 22), hypertensive patients with LVH (group C, n = 32) and coronary heart disease patients (group D, n = 33) with the volume sample placed at the bifurcation of the left main and left descending coronary artery. Coronary blood flow velocity (CBFV) was evaluated at rest, 2 minutes after dipyridamole (0.56 mg/kg, i.v.), and 2 minutes after aminophylline i.v. The ratio of dipyridamole to rest maximal diastolic velocity (D/R PDV) was considered the index of coronary blood flow reserve. It was found that D/R PDV was significantly less in groups C and D compared with that in groups A and B(D/R PDV, 1.84 +/- 0.57, 1.57 +/- 0.41 versus 2.59 +/- 0.70 and 2.22 +/- 0.58, respectively), with no difference in D/R PDV between groups C and D. Twenty-four out of 32 patients in group C with D/R PDV were less than 2.0 compared to 29 out of 33 patients in group D (P > 0.05). Significant negative correlation was found between D/R PDV, D/R PSV and interseptal thickness, left ventricular mass index in hypertensive patients. These data show that impaired CFR in hypertensive patients with LVH is comparable to that in patients with coronary heart disease.

Adult↗
PubMed2004

Oral antiplatelet therapy in cerebrovascular disease, coronary artery disease, and peripheral arterial disease.

CONTEXT: Atherothrombosis is a pathophysiologic process that results in clinical ischemic events affecting the cerebral, coronary, and peripheral arterial circulation. Antiplatelet agents, used alone or in combination, are effective in preventing recurrent vascular events among individuals with established vascular disease. OBJECTIVE: To summarize the current state of evidence regarding oral antiplatelet treatment in patients with cerebrovascular disease, coronary artery disease (CAD), and peripheral arterial disease. EVIDENCE ACQUISITION: Using the key terms acute coronary syndrome, atherothrombosis, ischemic stroke, myocardial infarction, MI, peripheral arterial disease, TIA, transient ischemic attack, unstable angina,aspirin,ticlopidine,dipyridamole, and clopidogrel, we searched the MEDLINE database as well as the trial register of the Cochrane Groups to identify studies published from 1960 to August 2004. We manually searched journals and abstract booklets; scrutinized reference lists of trials and review articles; and reviewed meta-analyses, scientific statements, and guidelines from official societies. EVIDENCE SYNTHESIS: Appropriate oral first-line antiplatelet therapy is aspirin for individuals with ST-segment elevation myocardial infarction; aspirin or clopidogrel for those with TIA or stroke, chronic stable angina, or peripheral arterial disease; and aspirin combined with clopidogrel for those with non-ST-segment elevation acute coronary syndrome. Aspirin combined with dipyridamole is a possible alternative for patients who experience a first episode of TIA or stroke in the absence of clinically apparent CAD. Although ticlopidine has been shown to be of benefit in various vascular conditions, its adverse-effect profile has limited its use. CONCLUSIONS: Aspirin, ticlopidine, clopidogrel, aspirin combined with clopidogrel, and aspirin combined with dipyridamole are effective in preventing recurrent vascular events among various subgroups of patients with vascular disease. Current clinical trial evidence favors the use of aspirin or clopidogrel as first-line agents for the majority of patients with vascular disease. Clinical trials evaluating combination antiplatelet therapies will direct future practice.

Administration, Oral↗
PubMed1995

Revascularization therapy for coronary artery disease. Coronary artery bypass grafting versus percutaneous transluminal coronary angioplasty.

Coronary artery bypass surgery relieves the symptoms of myocardial ischemia and prolongs survival of patients with more severe coronary artery disease. Randomized trials of surgical therapy have consistently shown that the benefits of surgical revascularization are proportional to the amount of myocardium affected by, or at risk for, ischemic injury. This risk is inferred from angiographically delineated coronary anatomy, estimates of left ventricular function, and physiologic testing. The population that may see a survival benefit from surgical revascularization has probably been expanded beyond that reported in the VA, CASS, and ECSS trials, due to improved perioperative care, longer graft survival, and the use of internal mammary artery grafts. Percutaneous transluminal coronary angioplasty revascularizes myocardium by dilating a stenotic segment of coronary artery. While successful in relieving the symptoms of myocardial ischemia, PTCA is hindered by the occurrence of abrupt vessel closure and the frequent development of restenosis. Furthermore, firm proof of a survival benefit, outside of emergency therapy for acute myocardial infarction, is not yet available. However, because the risk of procedure-related death or serious complication is lower than that seen with bypass surgery, PTCA provides a useful alternative revascularization method for patients with less extensive disease, in whom the risk of surgery may equal or exceed any beneficial effect. New technology and growing experience are widening the scope of percutaneous revascularization by extending the hope of symptomatic relief and survival benefit even to patients with extensive, severe coronary artery disease. Comparisons between surgical therapy and PTCA in select populations with single- and multivessel coronary artery disease have shown that PTCA is not as effective as surgery for long-term symptomatic control, and that it often requires repeat PTCA or cross-over to bypass surgery; however, long-term outcomes (i.e., death and myocardial infarction) are similar. The cost of treatment beginning with PTCA may be lower than that of initial surgery, even when the increased need for repeat revascularization is taken into account. Despite this, surgical bypass remains the mainstay of therapy for patients with severe coronary artery disease and a poor prognosis for survival, and will remain the fallback procedure for patients who repeatedly undergo failed PTCA. At the present time, revascularization should be offered on the basis of symptom severity (in the presence of medical therapy) and in accordance with the prognosis for survival as judged by the extent and severity of disease (Table VI). Percutaneous transluminal coronary angioplasty is preferred in patients who require revascularization but can obtain no proven benefit from bypass surgery. Coronary artery bypass surgery, using the internal mammary artery when possible, remains the revascularization method of choice for patients with more severe disease or whose disease is not amenable to treatment using percutaneous methods (Table VII).

Angioplasty, Balloon, Coronary↗
PubMed1998

[Early management of unstable coronary artery disease. Coronary angiography is the first measure in high-risk patients].

Unstable coronary artery disease is currently the major cause of admissions to coronary intensive care units, accounting for 30-40 per cent of cases. The underlying cause is rupture of an atherosclerotic plaque, coronary blood flow being impeded by a superimposed thrombus. New and more effective antithrombotic drugs are becoming increasingly available. Simultaneous early coronary angioplasty, stenting or bypass surgery provide the most effective amelioration of symptoms. Early revascularisation has not hitherto been found to reduce the risk of myocardial infarction or mortality in patients without signs of severe ischaemia. In this large category of cardiac patients, treatment strategy selection is of considerable importance to the effective utilisation of resources.

Angioplasty, Balloon, Coronary↗
PubMed1989

Weighted ventriculographic wall motion score for improved survival prediction in patients with coronary artery disease. Coronary Artery Surgery Study.

Global ventricular function parameters such as the ejection fraction and the sum of wall motion scores for segments of the left ventricle are excellent predictors of long-term survival in patients with coronary heart disease. These are usually determined from a monoplane right anterior oblique view. It was hypothesized that a biplane weighted wall motion score that included the left anterior oblique projection might better predict survival. A new score (BISCORE) was derived for 1,433 Mayo Clinic ventriculograms coded by the methods of the Coronary Artery Surgery Study (CASS). Weighting coefficients for each left ventricular segment were derived by the proportional hazards technique, and this resulted in the equation BISCORE = 120 - (8.6 x anterobasal + 3.4 x basal septum + 2.9 x apical + 2.7 x posterolateral + 2.4 diaphragmatic), which yielded a score from 0 (all segments aneurysmal) to 100 (all segments normal). This score stratified the original 1,433 patients into distinct groups by survival. As a single variable it was better than previous wall motion scores and ejection fraction at predicting survival. When prospectively applied to 5,172 Coronary Artery Surgery Study patients, this new score again proved to be a better predictor of survival than previous unweighted scores. Since the new score contains terms from the left anterior oblique ventriculographic projection, it is concluded that this projection adds information to that of the right anterior oblique projection regarding survival. Furthermore, this weighted score appears more highly associated with survival than unweighted scores.

Coronary Disease↗
PubMed1992

[Cholesterol--a marker for multiple risk factors? A comparison between coronary disease and coronary health].

Comparison was made in a cross-sectional study between 658 patients in whom coronary arteriography had shown (n = 304) or excluded coronary artery disease (CHD) (n = 354) and a clinically healthy group as controls (n = 1658), to assess possible risk factors. Patients aged 31-40 years with CHD had the highest total cholesterol levels (286 +/- 43 mg/dl) and the highest number of risk factors (3.6 +/- 0.9) compared to patients without CHD of the same age (204 +/- 30 mg/dl; 2.0 +/- 0.5) and healthy controls (216 +/- 45 mg/dl; 1.7 +/- 0.5) (P less than 0.001). In older patients with CHD, total cholesterol levels were lower (age group 61-70 years: 231 +/- 49 mg/dl), reaching about the same level as that of patients without CHD (232 +/- 54 mg/dl) or healthy controls of the same age (228 +/- 55 mg/dl). Furthermore, it was demonstrated that increased total cholesterol concentration can indicate the presence of other risk factors. It would thus appear that the level of total cholesterol in patients with CHD is decisively influenced by age and the presence of other risk factors.

Adult↗