A family history of coronary artery disease (CAD), especially when the disease occurs at a young age, is a potent risk factor for CAD. DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis. We performed a genomewide scan in 1,168 individuals from 438 families, including 493 affected sibling pairs with documented onset of CAD before 51 years of age in men and before 56 years of age in women. We prospectively defined three phenotypic subsets of families: (1) acute coronary syndrome in two or more siblings; (2) absence of type 2 diabetes in all affected siblings; and (3) atherogenic dyslipidemia in any one sibling. Genotypes were analyzed for 395 microsatellite markers. Regions were defined as providing evidence for linkage if they provided parametric two-point LOD scores >1.5, together with nonparametric multipoint LOD scores >1.0. Regions on chromosomes 3q13 (multipoint LOD = 3.3; empirical P value <.001) and 5q31 (multipoint LOD = 1.4; empirical P value <.081) met these criteria in the entire data set, and regions on chromosomes 1q25, 3q13, 7p14, and 19p13 met these criteria in one or more of the subsets. Two regions, 3q13 and 1q25, met the criteria for genomewide significance. We have identified a region on chromosome 3q13 that is linked to early-onset CAD, as well as additional regions of interest that will require further analysis. These data provide initial areas of the human genome where further investigation may reveal susceptibility genes for early-onset CAD.

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A survey of the rural community in Evans County, Georgia, revealed cervical arterial bruits in 72 (4.4 per cent) of 1620 persons 45 years of age of older without previous stroke, transient ischemic attacks, or overt ischemic heart disease. The prevalence of such asymptomatic bruits increased with age and was greater in women and persons with hypertension. We estimated the risk of stroke associated with cervical bruits during a six-year follow-up period, taking age and blood pressure into account. The presence of asymptomatic bruits was associated with a significantly higher risk of stroke in men but not in women, with odds ratios of 7.5 and 1.6, respectively. Despite the high risk of stroke among men with bruits, the correlation between the location of the bruits and the type of subsequent stroke was poor. Moreover, cervical bruits in men were a risk factor for death from ischemic heart disease. We suggest that asymptomatic cervical bruits are an indication of systemic vascular disease and do not themselves justify invasive diagnostic procedures or surgical correction of underlying extracranial arterial lesions.

SUMMARYGraded exercise stress tests performed on 650 consecutive patients with proven or suspected coronary disease undergoing evaluation by cardiac catheterization were correlated with clinical, hemodynamic, and angiographic findings. Among 451 patients with significant coronary stenosis, 332 (74%) had interpretable stress tests and 65% of these were positive (sensitivity). The rate of "false positives" was 8%.The clinical syndrome of typical angina identified significant coronary disease in 89% of the patients, and 58% of that group had a positive exercise test defined by objective electrocardiographic criteria.Patients were not eliminated from this study because of recent digitalis ingestion. Although a higher frequency of uninterpretable exercise tests was found in this group (40%), the test results reflected more severe coronary disease. None of the patients with "false positive" tests were taking digitalis. It is concluded that recent digitalis ingestion should not be considered a contraindication for exercise stress testing.Among the patients with interpretable exercise tests, the angiographic severity of coronary artery disease correlates strongly with the frequency of positive tests (40%, 66%, and 76%, with 70% or greater occlusion of one, two or three vessels respectively). Left main coronary stenosis of 70% or greater was associated with more severe ST segment changes, inability to achieve target heart rate during stress, and a lower maximum heart rate during exercise. The angiographic occurrence of collateral vessels was related to the extent of coronary disease and was associated with a higher percentage of positive exercise tests; no protective effect of collateral circulation could be demonstrated. Patients with abnormal resting hemodynamics or left ventricular asynergy had no significant difference in the frequency of positive tests after adjustment for the angiographic severity of disease.

Serial postoperative ECGs were reviewed for all patients undergoing saphenous vein-coronary artery bypass graft (CABG) during 1969-71. Only the development of new pathologic Q waves were accepted as indicative of definite acute myocardial infarction (AMI). ST-T changes regardless of characteristics were not accepted as evidence of AMI. Operative mortality was 11% (27/253) with 59% (10/17) of those autopsied having AMI. Autopsy findings showed no false positives by ECG. Of survivors, 15% (33/220) had AMI. Another 2% (five) developed leftbundle conduction abnormalities and were considered probable for AMI. Among all patients having CABG, 20% (49/243) had AMI by ECG or autopsy.Comparing patients with and without AMI, there was no significant difference in coronary risk factors, hemodynamic data, number of vessels diseased, or site(s) of grafts. There was a significant difference in preoperative functional class for angina in the two groups. Seventy-six percent of those in the MI group had New York Heart Association class IV chest pain, whereas only 52.6% of the group without MI were class IV (P < 0.05). In those with triple grafts (14 patients), five had AMW (36%) compared to 14% (20/143) with one or two grafts (P < 0.02). Of patients with a pump time greater than 120 min. 29% (8/28) had AMI compared to 11% (16/146) with shorter pump times (P < 0.02). A significantly larger number of the MI group developed class IV congestive heart failure postoperatively than the group without MI (13 vs 2%, P < 0.02).Despite the use of stringent criteria, this study shows that AMI complicating CABG is a common event. Those developing AMI at surgery had more severe chest pain preoperatively, had prolonged pump times, and a significantly larger number received triple grafts. Postoperatively, there was a higher incidence of severe congestive heart failure in those having an infarct at surgery.