Drinking habits and death. The Yugoslavia cardiovascular disease study.

In a prospective study of more than 10000 Yugoslav men it was found that consumption of alcoholic beverages was inversely related to non-sudden death from coronary heart disease (CHD) and positively related to death from trauma. The consequence was an apparently U-shaped relation between alcohol consumption and death, the lowest mortality being among moderate drinkers. Excess mortality from trauma was evident only among men under 55 and only for those who reported at entry to the study that they had been drunk during the preceding week. Alcohol consumption as reported at entry was unrelated to subsequent mortality from liver cirrhosis or any form of cancer. An enlarged liver, however, was associated with higher death rates for liver cirrhosis. This raises the possibility that some of the men were heavy drinkers preceding their entry to the study but were no longer drinking heavily at the time of entry. Enlarged liver, however, was also related to hypertension and to chronic obstructive pulmonary disease and thus was not a specific indicator of alcohol abuse in this population. Recent drunkenness but not frequency of drinking was related to death from trauma and liver cirrhosis and to sudden CHD death. In short, both the pattern of drinking and the usual level of alcohol consumption appear to be related to mortality in this population.

The Yugoslavia Cardiovascular Disease Study. 3. Death by cause and area.

In the seven years following initial examination (1964--65) 758 deaths were observed in 11,121 Yugoslav men aged 35--62. The mortality rate was similar to that found for men in the Framingham (Massachusetts) study. However, coronary heart disease (CHD) mortality was much lower in Yugoslavia but mortality from cancer, accidents and violence and respiratory disease was much higher. The excess cancer mortality was chiefly from stomach cancer. The excess respiratory mortality was from both tuberculosis and chronic obstructive respiratory disease. Within Yugoslavia there were area differences in mortality by cause but little difference in total mortality: in Tuzla (Bosnia) there was a higher respiratory disease mortality but a lower mortality from accidents and violence than in Remetinec (Croatia). In the rural areas of the study there was a higher mortality from respiratory diseases and accidents and violence than in urban areas but a counterbalancing lower mortality from cardiovascular diseases. The low coronary death rates and high cancer of the stomach death rates in this population present an important epidemiological challenge.

Evolution and funding of the Coronary Drug Project.

The evolution of the CDP from its origin in 1960 to its completion in 1975 has been recounted. The inextricable interrelationships of the scientific planning and conduct of this trial with the budgetary considerations and uncertainties as it proceeded are described to illustrate some of the dynamic forces that determine whether or not such large-scale trails can be brought to successful completion. A clear message from this experience is that a long-term clinical trial needs full advance scientific and administrative discussion and an understand of the resources required to bring it to its completion. Continuing scientific and administrative commitment are also essential to assure that the needed resources are provided over the course of the trial. The experience gained in this long-term clinical trial involving 53 clinics, a Coordinating Center, Central Laboratory, ECG Reading Center, and Drug Procurement and Distribution Center has provided a basic model for the new generation of clinical trials that have since been undertaken by the NHLBI.

Drinking habits and coronary heart disease: the Yugoslavia cardiovascular disease study.

In a prospective study of more than 10,000 Yugoslav men residing in Bosnia and Croatia, who were first examined in 1964--1965, consumption of alcoholic beverages was related inversely to the subsequent appearance of coronary heart disease clinically manifest as myocardial infarction or nonsudden coronary heart disease death. Consumption of alcoholic beverages was not so related to sudden cardiac death. Men who drank most frequently had half the subsequent incidence of overall coronary heart disease as men who seldom or never drank. This finding was true for urban residents only. Serum cholesterol and Quetelet index were also related to coronary heart disease in urban areas but not in rural areas. The inverse relation of alcohol consumption to coronary heart disease incidence was statistically significant even after taking into account differences in blood pressure, serum cholesterol levels, cigarette smoking and other variables. The apparent absence of protection against sudden death may be due to chance or it may reflect the deleterious effects of high alcohol consumption on the myocardial cells and increased vulnerability to lethal arrhythmias in an especially lean population. There is, in fact, a specific association of recent drunkenness with sudden death in this population. Conceivably, the acute effect of heavy drinking may be a dominant factor in the incidence of sudden death for this population.

Drinking habits and other characteristics: the Yugoslavia Cardiovascular Disease Study.

In two large general populations of Yugoslav men from Tuzia, Bosnia, and Remetinec, Croatia, examined in 1964-1965, it was found that a greater alcohol consumption was accompanied by higher blood pressures, higher pulse rates, and higher concentrations of serum cholesterol and hematocrit. A greater consumption was also associated with an enlarged liver, as well as a higher prevalence rate of chronic bronchitis and thrombophlebitis. All these were statistically significant even after allowing for differences in cigarette smoking and demographic characteristics. Pulse rate, liver size, and varices appear to be specifically associated with a history of episodes of drunkenness. There were significant differences in drinking habits by place of residence, religious background, years of schooling, and kind of work. These were allowed for in evaluating the relationship of drinking to other characteristics. Two anomalous findings were low prevalence rates for diabetes and gastritis among those drinking most frequently.

The Coronary Drug Project. Role of the National Institutes of Health.

A clinical trials staff within an Institute is essential for adequate participation in and monitoring of any large cooperative clinical trial supported by that Institute. At minimum such a staff should consist of a medical scientist with professional interests and experience in clinical trials methodology; a biometrician with direct experience and interest in the design, large-scale data collection, data analysis, and quality control needs of such trials; a contract specialist; and additional consultants in the technical areas related to the clinical disease or intervention study, such as pharmacology, laboratory operations, computer science, or other areas. The continuity of professional development and experience of such a staff is essential to expand the capabilities for participation and advancement of this rapidly developing science of the design, organization, and conduct of cooperative clinical trials.

The Yugoslavia cardiovascular disease study. II. Factors in the incidence of coronary heart disease.

In a 7-year follow-up of 11,121 Yugoslav men first examined in 1964-1965 when they were 35-62 years old, it was found that the incidence of coronary heart disease (CHD) was one-fourth that of a comparable Framingham (USA) group. Incidence in rural men was only 59% of urban men. In both urban and rural groups, men with higher blood pressures had greater CHD incidence, and cigarette smoking was also associated with greater incidence. In the urban but not the rural groups serum cholesterol and weight/height were also CHD risk factors. Levels of serum cholesterol and weight were lower in urban Yugoslavia than Framingham and lowest in rural Yugoslavia. At the same levels of these characteristics Framingham incidence was 3 times that in Yugoslavia. At the very low rural levels of weight and blood pressure CHD incidence was the same in urban as rural Yugoslav groups.

Diet and its relation to coronary heart disease and death in three populations.

Baseline 24-hour dietary recalls from 16,349 men ages 45-64 years who had no evidence of coronary heart disease (CHD) were obtained in three prospective studies: the Framingham Study (859 men), the Honolulu Heart Study (7272 men) and the Puerto Rico Heart Health Program (8218 men). These men were followed for up to 6 years for the first appearance of CHD or death. Men who had a greater caloric intake or a greater caloric intake per kilogram of body weight were less likely to develop CHD manifest as myocardial infarction (MI) or CHD death, even though men of greater weight were more likely to develop CHD. This may reflect the benefit of greater physical activity. Men who consumed more alcohol were less likely to develop CHD, but more likely to die of causes other than CHD, particularly in the Honolulu study. In the Honolulu and Puerto Rico studies, but not in the Framingham study, men who consumed more starch were less likely to develop MI or CHD death. There was an inverse relation between starch intake and serum cholesterol, but it was too weak to explain fully the inverse starch-CHD association. There was also no evidence that the inverse relation between starch intake and incidence of CHD in the Honolulu and Puerto Rico studies was an indirect result of differences in fat intake. While the findings suggest additional areas for research, none of them would lead to an alteration of currently recommended preventive diets that emphasize lowering fat intake, because in isocaloric diets the logical way to balance a decreased fat intake is to increase the consumption of foods containing starch.

Alcohol and blood lipids. The cooperative lipoprotein phenotyping study.

Data from five study populations participating in the Cooperative Lipoprotein Phenotyping Study indicate strong relations between reported alcohol consumption and blood-lipids. Alcohol consumption was positively associated with high-density-lipoprotein cholesterol level in all populations (r from 0-16 to 0-30), the lipid level appearing to be a graded response even over the low levels of alcohol consumption reported. Less strong but consistently negative correlations were found with low-density-lipoprotein cholesterol. Plasma-triglycerides showed a modest positive correlation with alcohol. The five populations were those of the Albany, Evans County, Framingham, Honolulu, and San Francisco Studies.

HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study.

The relation between coronary heart disease (CHD) prevalence and fasting lipid levels was assessed by a case-control study in five populations with a total of 6859 men and women of black, Japanese and white ancestry drawn from subjects aged 40 years and older from populations in Albany, Framingham, Evans County, Honolulu and San Francisco. In each major study group mean levels of high density lipoprotein (HDL) cholesterol were lower in persons with CHD than in those without the disease. The average difference was small -- typically 3-4 mg/dl -- but statistically significant. It was found in most age-race-sex specific groups. The inverse HDL cholesterol-CHD association was not appreciably diminished when adjusted for levels of low density lipoprotein (LDL) cholesterol and triglyceride. LDL, totoal cholesterol and triglycerides were directly related to CHD prevalence; surprisingly, these findings were less uniformly present in the various study groups than the inverse HDL cholesterol-CHD association.