Alcohol consumption, serum low density lipoprotein cholesterol concentration, and risk of ischaemic heart disease: six year follow up in the Copenhagen male study.

Abstract

Objectives--To investigate the interplay between use of alcohol, concentration of low density lipoprotein cholesterol, and risk of ischaemic heart disease.

Design--Prospective study with controlling for several relevant confounders, including concentrations of other lipid fractions.

Setting--Copenhagen male study, Denmark.

Subjects--2826 men aged 53-74 years without overt ischaemic heart disease.

Main outcome measure--Incidence of ischaemic heart disease during a six year follow up period.

Results--172 men (6.1%) had a first ischaemic heart disease event. There was an overall inverse association between alcohol intake and risk of ischaemic heart disease. The association was highly dependent on concentration of low density lipoprotein cholesterol. In men with a high concentration ([greater than or equal to]5.25 mmol/l) cumulative incidence rates of ischaemic heart disease were 16.4% for abstainers, 8.7% for those who drank 1-21 beverages a week, and 4.4% for those who drank 22 or more beverages a week. With abstainers as reference and after adjustment for confounders, corresponding relative risks (95% confidence interval) were 0.4 (0.2 to 1.0; P[less than]0.05) and 0.2 (0.1 to 0.8; P[less than]0.01). In men with a concentration [less than]3.63 mmol/l use of alcohol was not associated with risk. The attributable risk (95% confidence interval) of ischaemic heart disease among men with concentrations [greater than or equal to]3.63 mmol/l who abstained from drinking alcohol was 43% (10% to 64%).

Conclusions--In middle aged and elderly men the inverse association between alcohol consumption and risk of ischaemic heart disease is highly dependent on the concentration of low density lipoprotein cholesterol. These results support the suggestion that use of alcohol may in part explain the French paradox.

Introduction

Several epidemiological studies have shown an inverse association between alcohol consumption and risk of ischaemic heart disease, the association often being described as J or U shaped.(1)

Epidemiological studies have shown a positive correlation between the serum concentration of low density lipoprotein cholesterol and risk of ischaemic heart disease.(2) A high intake of saturated fat is associated with an increase in concentration of low density lipoprotein cholesterol and subsequently an increased risk of ischaemic heart disease. Despite a high intake of saturated fat, in some parts of France the incidence of ischaemic heart disease is quite low, with a rate comparable with that in Japan. This apparent discrepancy between a risky lifestyle and a low risk of ischaemic heart disease has been named the French paradox. The suggestion of a French paradox is based on ecological studies.(3) (4) (5)

The low incidence of ischaemic heart disease in France might be the result of regular consumption of alcohol.(3) (4) (5) A comparative ecological study of 21 developed, relatively affluent countries, showed that France had the highest consumption of wine and total alcohol per capita.(5) The high fat and alcohol consumption and the low risk of ischaemic heart disease indicate the existence of an interaction between the concentration of low density lipoprotein cholesterol, alcohol consumption, and risk of ischaemic heart disease. To our knowledge, this issue has not previously been studied prospectively.

We investigated this interplay in a cohort of Danish men. As recently reviewed by Criqui and Ringel,(5) in Denmark the average intake of dietary fat is higher than that in France, and also the average consumption of alcohol is quite high but lower than that in France. We took into account the type of beverage consumed, other lipid fractions particularly high density lipoprotein cholesterol, and several other potentially confounding factors.

Subjects and methods

The Copenhagen male study was set up in 1970 as a prospective cardiovascular study.(6) (7) The men came from 14 large work places in Copenhagen.(6) All employed men (6125) aged 40 to 59 years (mean 48 years) were invited--from the managing director to the porter. A total of 5249 men participated (87%).

In 1971-2 the cohort was re-examined; the participation rate was 90.5%. Information was acquired about average daily use of alcohol during the preceding year. At that time alcohol consumption was reported in five categories: [less than]1, 1-2, 3-5, 6-10, and [greater than]10 beverages a day. Thus, from these categories it was not possible to identify abstainers. The 1971-2 data were used to estimate changes in alcohol habits over time.

In 1985-6 a new baseline was established for the study and has been used in this report. All survivors from the 1970 study were traced by means of the Danish central population register. Between June 1985 and June 1986 all 4505 survivors (except 34 emigrants) from the original cohort were invited to take part in the current study. In total 3387 (75%) men participated and gave informed consent; their mean (range) age was 63 (53-74) years. Each subject was interviewed by a physician (HOH) about a previously completed questionnaire and examined, with height, weight, and blood pressure being measured and an electrocardiogram being recorded. A venous blood sample was taken after the subject had fasted for at least 12 hours for measurements of serum lipid concentrations, Lewis phenotypes, and serum cotinine concentration.

Total weekly alcohol consumption was calculated from questionnaire items about average alcohol consumption on weekdays and at weekends. Intakes of beer, wine, and spirits were recorded separately. One drink corresponded to 10-12 g ethanol. The men classed themselves as having never smoked, as having smoked, or as current smokers. Current tobacco smoking was calculated from information about the number of cigarettes, cheroots, cigars, or the weight of pipe tobacco smoked daily. One cigarette was taken as equivalent to 1 g tobacco, one cheroot as 3 g, and one cigar as 4 g. As previously estimated from serum cotinine concentrations, the validity of tobacco reporting was high.(8) The men also classed themselves as being physically active for four or more hours a week or for less than four hours a week. According to a system by Svalastoga,(9) later adjusted, the men's social class was given as one of five social groups on the basis of education and job profile. The classes ranged from class I (self employed subjects with at least 21 employees, white collar workers with at least 51 subordinates, and men with an academic degree) to class V (unskilled blue collar workers such as unskilled labourers, mechanics, and drivers).

Concentrations of serum lipids, high density lipoprotein cholesterol, and triglycerides were determined by using standardised methods.(10) (11) (12) (13) Low density lipoprotein cholesterol was calculated from the above.(14) Lewis typing was carried out on erythrocytes by using a saline haemagglutination technique in test tubes with monoclonal a and b antibodies (Seraclone, Biotest, Dreieich, Germany).(15) …