Background: Some large epidemiological studies have shown an increase in mortality at low levels of total and LDL cholesterol. It has been speculated that low cholesterol levels may play a causative role in this association. To investigate this question, we analyzed all deaths occurring among middle-aged men in the Münster Heart Study (PROCAM), one of the largest prospective epidemiological studies of coronary heart disease risk markers in Europe.
Methods and results: In the Münster Heart Study, 10,856 men aged 36 to 65 years at study entry (46.8+/-7.3 years [mean+/-SD]) were followed for 4 to 14 years (7.1+/-2.4 years). During this period, 313 deaths occurred--46 from myocardial infarction, 48 from suspected or definite sudden cardiac death, 14 from cerebrovascular disease, and 10 from other diseases of the circulatory system. There were 121 deaths from cancer and 33 deaths from violent causes (injuries in 16, suicide in 14, and homicide in 3 cases). Death in 29 cases occurred from other causes and was unexplained in 12 cases. Total cholesterol, LDL cholesterol, and the LDL/HDL ratio showed a J-shaped relationship with total mortality. At high total and LDL cholesterol concentrations, increased mortality was due to increased coronary deaths. At low total and LDL cholesterol concentrations, increased mortality was seen in smokers only and was explained by an increase in smoking-related cancer deaths.
Conclusions: The increase in mortality at low levels of total and LDL cholesterol among middle-aged men in the Münster Heart Study is explained by an increase in smoking-related cancer deaths among smokers.