We studied cancer incidence and mortality from cancer and coronary heart disease in relation to serum cholesterol levels in 92,710 individuals followed-up in the nationwide Swedish Cancer Register and the Swedish Cause of Death Register for 18-20 years. According to Cox's proportional hazard model, total cancer incidence and total cancer mortality were negatively correlated to serum cholesterol level (P less than .001). The negative correlations were most pronounced during the first years of follow-up. Cancer mortality data showed a stronger negative association to cholesterol than did incidence data during the first 10 years of follow-up (P less than .05). Mortality from coronary heart disease was positively correlated to serum cholesterol (P less than .001) during the entire follow-up. In contrast to most studies that were based on mortality data, our results of the comparison of incidence and mortality data of the same cohort are in agreement with those of a cholesterol-lowering effect of a preclinical cancer. Efforts by investigators and clinicians to lower serum cholesterol to prevent cardiovascular disease are, according to the present findings, not likely to increase cancer mortality risks but would extend life, irrespective of cause of death.
OBJECTIVE--To determine whether total serum cholesterol concentration predicts mortality from injuries including suicide. DESIGN--Cohort study of men and women who had their serum cholesterol concentration measured as part of a general health survey in V?rmland, Sweden in 1964 or 1965 and were followed up for an average of 20.5 years. SUBJECTS--Adults participating in health screening in 1964-5 (26,693 men and 27,692 women). The study sample was restricted to subjects aged 45-74 years during any of the 20.5 years of follow-up. MAIN OUTCOME MEASURES--Serum cholesterol concentration. Deaths from all injuries and suicides during three periods of follow up (0-6 years, 7-13 years, and 14-21 years) according to the Swedish mortality register in subjects aged 45-74. Adjustment was made for prevalent cancer (identified from the Swedish cancer register) at the time of a suicide. RESULTS--A strong negative relation between cholesterol concentration and mortality from injuries was found in men during the first seven years of follow up. The relative risk in the lowest 25% of the cholesterol distribution was 2.8 (95% confidence interval 1.52 to 4.96) compared with the top 25%. Most of the excess risk was caused by suicide with a corresponding relative risk of 4.2 (p for trend = 0.001). Correction for prevalent cancer did not change the results. Events occurring during the latter two thirds of the 20.5 years of follow up were not predicted. In women no relation between cholesterol concentration and mortality from injuries was found. CONCLUSIONS--Together with observations from intervention trials the findings support the existence of a relation between serum cholesterol concentration and suicide. The causality of such a relation is, however, not resolved.
We studied the risk of colorectal cancer in relation to serum cholesterol and beta-lipoprotein in more than 92,000 Swedish subjects less than 75 years old. The cohort was examined between 1963 and 1965 and followed by means of the Swedish Cancer Register until 1979. During this period, 528 colon cancers and 311 rectal cancers developed. A positive association was observed between the serum cholesterol level and the risk of rectal cancer among men (P less than 0.05), with a relative risk of 1.65 in men with levels greater than or equal to 276 mg per deciliter (7.1 mmol per liter). An association was also observed between the serum beta-lipoprotein level and the risk of rectal cancer among men (P less than 0.05). When cholesterol and beta-lipoprotein levels were considered together, they were associated with both rectal and colon cancer in men. The relative risk in men with both cholesterol greater than or equal to 250 mg per deciliter (6.5 mmol per liter) and beta-lipoprotein greater than or equal to 12 units (2.2 g per liter) was 1.62 for colon cancer (95 percent confidence interval, 1.18 to 2.22) and 1.70 for rectal cancer (1.18 to 2.44). Similar trends were observed in women, although they were not statistically significant.
The objective of the Värmland Study was to examine how serum cholesterol can be used to predict short- and long-term ischemic heart disease (IHD) mortality, especially in women aged 65 or older. This prospective cohort study involved about 20 years of follow-up after a single determination of serum cholesterol and included participants in a health screening undertaken from 1962 to 1965 (48,076 men, 48,732 women). The main outcome measures were mortality from IHD, acute myocardial infarction (MI), and chronic ischemic heart disease (CIHD). An IHD mortality trend was associated with increasing cholesterol levels for people younger than 65 years, and was more pronounced for men than women. For people 65 years or older, there was a weak trend for men, but not even a tendency for women. Regarding acute MI, significant trends were observed for males as well as females, for young as well as old people. A mild CIHD mortality trend was observed for young men. Otherwise no significant trend was seen.
OBJECTIVE--To determine whether serum sialic acid concentration may be used to predict short and long term cardiovascular mortality. DESIGN--Prospective study on all men and women who had their serum sialic acid concentration measured as part of a general health survey in 1964 or in 1965. All were followed up for an average of 20.5 years. SETTING--Geographical part of the county of V?rmland, Sweden. SUBJECTS--Residents in the area participating in a health check up in 1964-5 (27,065 men and 28,037 women), of whom 372 men (169 with incomplete data and 203 lost to follow up) and 345 women (143 and 202 respectively) were excluded; thus 26,693 men and 27,692 women entered the study. The study sample was restricted to subjects aged 40-74 during any of the 20 years' follow up. MAIN OUTCOME MEASURES--Serum sialic acid concentration, serum cholesterol concentration, diastolic blood pressure, body mass index at the general health survey visit; cardiovascular and non-cardiovascular deaths during three periods of follow up (0-6 years, 7-13 years, and 14-20 years), according to the Swedish mortality register, in subjects aged 45-74. RESULTS--Mean serum sialic acid concentration (mg/100 ml) was 68.8 (SD 8.0) for men and 69.2 (8.0) for women; the average concentration increasing with age in both sexes. A total of 5639 (21%) men and 3307 (12%) women died during the follow up period, in whom death in 3052 (54%) men and 1368 (41%) women was from cardiovascular causes. During short (0-6 years), medium (7-13 years), and long (14-20 years) term follow up the relative risk of death from cardiovascular disease increased with increasing serum sialic acid concentration. The relative risk (95% confidence interval) associated with the highest quartile of sialic acid concentration compared with the lowest quartile was 2.38 (2.01 to 2.83) in men and 2.62 (1.93 to 3.57) in women. Similar results were found for deaths from non-cardiovascular disease with relative risks of 1.50 (1.34 to 2.68) in men and 1.89 (1.57 to 2.28) in women, but these relative risks were significantly lower than those for deaths from cardiovascular disease (p less than 0.001 and p less than 0.005 respectively). In multivariate analysis of total mortality and of cardiovascular mortality with sialic acid concentration, serum cholesterol concentration, diastolic blood pressure, and body mass index as independent variables the impact of sialic acid concentration was virtually the same as in univariate analysis. CONCLUSION--Serum sialic acid concentration is a strong predictor of cardiovascular mortality. A possible explanation of these findings is that the serum sialic acid concentration may reflect the existence or the activity of an atherosclerotic process, and this may warrant further investigation.
Comment In: BMJ. 1991 Mar 2;302(6775):533-42012866
To investigate the nature of the relationship between serum sialic acid concentration and cardiovascular mortality, the risks for coronary heart disease (CHD) and stroke were assessed separately in 26,693 men and 27,692 women followed during 20.5 years. Diastolic blood pressure, total cholesterol and body mass index were used as covariates in a person-year-based Poisson model. Relative risks for CHD mortality associated with the highest sialic acid quartile was 1.76 (95% confidence interval (CI): 1.58-1.96) in men and 1.94 (95% CI: 1.61-2.34) in women. Corresponding figures for stroke were 1.62 (95% CI: 1.26-2.09) and 1.68 (95% CI: 1.28-2.21) respectively. No significant patterns related to the age at entry was observed. For both genders, and both endpoints, diastolic blood pressure was associated with higher relative risk than sialic acid, and body mass index and serum total cholesterol were less predictive. Serum sialic acid concentration predicts both death from CHD and stroke in men and women independent of age. The biological foundation of this finding remains unclear.
The variation of serum cholesterol level was studied in a cohort of 16,281 individuals, with repeated measurements of cholesterol. The mean correlation coefficient between the two cholesterol values taken with a six-week interval on two occasions was 0.74. This correlation coefficient indicates a short-term variation of serum cholesterol, and reflects measurement errors and intra-individual fluctuations in cholesterol level, eg due to variations in dietary habits. The correlation coefficient for serum cholesterol values taken with a two-year interval was 0.66 and reflects a long-term variation. The ratio between these coefficients may be interpreted as a rough estimate of a correlation between the true cholesterol levels at a two-year interval, free from measurement errors and short-term intra-individual variations in dietary habits. The validity was assessed with the correlation between a single serum cholesterol value and mortality from myocardial infarction, in a cohort of 92,839 individuals followed-up for 14-16 years. The relative risks (RR) for death in myocardial infarction increased with increasing cholesterol levels. The RRs were in accordance with the well-established correlation between serum cholesterol and death from myocardial infarction. The results indicated a fairly high stability of the cholesterol level in blood and that the cholesterol values in the studied cohort were not less reliable than in comparable studies.
The role of serum cholesterol in predicting the risk of stroke is unclear and may depend on the subtype of the disease. In 1964 to 1965, 54,385 Swedish men and women participated in a health survey with serum cholesterol and diastolic blood pressure determinations. The Swedish mortality register was used to identify causes of death in this cohort during 20.5 years of follow-up (1964 to 1985). A person-year-based Poisson model was used for multivariate analysis. Relative risk increased with decreasing serum cholesterol level for subarachnoid hemorrhage in men and for cerebral hemorrhage in women but not for subarachnoid hemorrhage in women. For cerebral hemorrhage in men, the risk function was U-shaped. Adjustment for diastolic blood pressure did not significantly change the relation between the risk for any of the different stroke types and the cholesterol level. A low cholesterol level predicts death from intracranial bleeding, but the data suggest that there is differing risk pattern for men and women.