The lower your cholesterol in midlife, the better you are off in old age

With up to 39 years of follow-up data in hand, Finnish researchers can say men who had naturally low cholesterol levels in early middle age are more likely to survive and have a higher quality of life in old age, although the implications for cholesterol-lowering treatment decisions are not clear, according to a new study in the Sept. 1, 2004 issue of the Journal of the American College of Cardiology.

“The lower your cholesterol in midlife, the better you are off in old age, and the higher the probability that you will even reach old age,” said Timo E. Strandberg, M.D., Ph.D., at the University of Helsinki in Finland.

The researchers took advantage of cholesterol test results from 3,277 healthy businessmen that had been collected in the 1960s and 1970s, vital statistics records on the Finnish population, as well as the goodwill of participants in the original research.

“The original data has luckily survived over the decades,” Dr. Strandberg said. “In 2000 and 2003 we contacted the survivors, now in their 70s and 80s, by questionnaire, and some 80 percent responded, even enthusiastically! We have a very good population register in Finland, so it is easy to make contact for research purposes. Finns are also usually interested in taking part in research,” Dr. Strandberg said.

A baseline cholesterol value of five millimoles per liter (193 mg/dl) or lower was associated with a 25 percent reduction in total mortality. In old age, the physical component summary score of a commonly used quality of life questionnaire (RAND-36) was significantly better in the lowest baseline cholesterol group. No difference was found in the mental component summary score.

Since the original study included only Finnish men who were mostly business executives, the researchers cannot be sure they would see similar results among women or other social or ethnic groups. They used multivariate statistical analysis to try to account for potential effects of any other characteristics of the men with low cholesterol levels. Dr. Strandberg said the fact that all the men came from similar backgrounds means it is unlikely the differences they saw were related to socioeconomic factors.

Dr. Strandberg said the very long follow-up should ease concerns about low cholesterol being associated with certain health risks, though he noted that the study did not include participants with extremely low cholesterol. While this study documents positive outcomes among men with naturally low cholesterol, it does not directly address questions about when to use drugs to reduce cholesterol levels.

“Our results are part of the picture which shows that keeping cholesterol in check is in general good for your arteries and body. Using drugs to lower cholesterol should, however, always be based on total cardiovascular risk,” Dr. Strandberg said.

In an editorial in the journal, M. H. Criqui, M.D., M.P.H. and B. A. Golomb, M.D., Ph.D. at the University of California at San Diego wrote that the long-term follow-up offers confirmation that low cholesterol in early middle age is associated with longer life, at least among healthy men with higher incomes. However, they caution that it may not be appropriate to try to extend the results to other groups or to cholesterol-lowering drug therapy.

“We think it's unwarranted for persons without cardiovascular disease to take this data and say, 'Well, if low cholesterol in mid-life is really important, I'm going to lower my cholesterol as low as it can go using a powerful drug. Some people agree with this idea, but we are more conservative. There hasn't been long enough experience with drug therapy in lower risk persons to know if benefits clearly outweigh risks in the long term,” Dr. Criqui said.

Dr. Criqui emphasized that this was not a treatment study and that cholesterol treatment decisions need to include measurements of HDL cholesterol, as well as other cardiovascular risk factors.

Vera Bittner, M.D., M.S.P.H., F.A.C.C. at the University of Alabama at Birmingham, who was not connected with this study, commented that although this study included only men with high socioeconomic backgrounds, it did overcome some shortcomings of other studies of people with low cholesterol.

“The current study is important because a) it provides very long-term mortality follow-up (up to 39 years) in a group of men who were young to middle aged (30–45) at their initial evaluation between 1968 and 1973, b) because these men were healthy at study entry (thus minimizing the chance that the data were muddled due to concomitant disease) and c) because the study largely precedes cholesterol-lowering therapy (in other words, these men had “naturally low cholesterol”). This study thus allows us to look at the prognosis of “naturally low cholesterol” long-term. Whether low cholesterol as a result of medication use has the same good long-term prognosis is unknown and we clearly cannot extrapolate such an effect from these data.”

The Päivikki and Sakari Sohlberg Foundation, the Helsinki University Central Hospital, and the Finnish Foundation for Cardiovascular Research have provided financial support. Dr. Strandberg is a senior research fellow of the Academy of Finland. All authors have cooperated with companies marketing cholesterol-lowering drugs.

The American College of Cardiology, a 31,000-member nonprofit professional medical society and teaching institution, is dedicated to fostering optimal cardiovascular care and disease prevention through professional education, promotion of research, leadership in the development of standards and guidelines, and the formulation of health care policy.