High lipoprotein (a) levels increased the risk for coronary heart disease in middle-aged men
ACP J Club. 1991 Mar-Apr;114:63. doi:10.7326/ACPJC-1991-114-2-063
Rosengren A, Wilhelmsen L, Eriksson E, Risberg B, Wedel H. Lipoprotein (a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men. BMJ. 1990;301:1248-50.
To investigate serum lipoprotein (a) concentration as a risk factor for coronary heart disease among middle-aged men.
Case-control study, with the sample derived from a cohort followed prospectively for 6 years.
Population-based screening program in Gothenburg, Sweden.
In 1983, a random half of the men of Gothenburg who were aged 50 years (n = 1016) were invited for screening for coronary heart disease risk factors; 776 (76%) attended. By 31 December 1989, 31 of the attendees had had a nonfatal myocardial infarction (n = 22) or had died from coronary heart disease (n = 9). These cases were ascertained through the register of myocardial infarctions in Gothenburg and through death certificates. 4 controls for each case were randomly selected from the sample. Potential cases and controls were excluded if they had a history of previous myocardial infarction (4 cases, 2 controls) or incomplete data (1 case, 13 controls).
Assessment of risk factors
At the baseline evaluation in 1983-1984, the investigators recorded fasting total serum cholesterol and triglyceride levels, blood pressure, body mass, smoking habits, family history of cardiovascular disease, history of diabetes, and use of antihypertensive drugs. Additional blood samples were frozen at -70 °C. After 6 years, serum specimens were thawed and lipoprotein (a) was measured, without reference to the case-status of the person.
The mean serum lipoprotein (a) concentration was higher in the cases than in the controls (277.7 vs 172.7 mg/L; mean difference, 105.0 mg/L [95% CI 18.0 to 192.0 mg/L]). Multiple logistic regression analysis showed that coronary heart disease was associated with body mass index (P = 0.023), history of a myocardial infarction in a mother (P = 0.039), smoking (P = 0.01), treatment for hypertension (P = 0.023) and serum lipoprotein (a) (P = 0.01).
A high level of serum lipoprotein (a) was an independent risk factor for the development of coronary heart disease in a sample of Swedish men who were aged 50 years.
Sources of funding: Swedish Medical Research Council; Swedish National Association Against Heart and Chest Diseases; Gothenburg Medical Society; Knut and Alice Wallenberg Foundation.
Address for article reprint: Dr. A. Rosengren, Department of Medicine, University of Gothenburg, Östra Hospital, S-416 85 Gothenburg, Sweden.
The study by Rosengren and colleagues corroborates the findings of other case-control studies but has the methodologic advantage of studying persons from a prospective population-based cohort. Therefore, we can be confident that elevated lipoprotein (a) levels definitely precede the coronary event.
This study however, does not address several other criteria that must be satisfied before we can say that lipoprotein (a) is a cause of coronary heart disease. First, the study did not show a dose-response relation between the level of lipoprotein (a) and the risk for coronary heart disease. Second, 2 known risk factors for heart disease, low-density lipoprotien and high-density lipoprotein cholesterol, were not included, and their role as potential confounders could not be assessed. Finally, as the authors note, no evidence exists that reducing lipoprotein (a) will result in a decreased risk for disease.
We must await further evidence before we draw conclusions about the causal role of lipoprotein (a) in heart disease and before we alter our clinical practice.
Arthur T. Evans, MD, MPH
University of North CarolinaChapel Hill, North Carolina, USA