As this 40-year longitudinal study illustrates, when measuring the correlation between specific risk factors on specific forms of mortality, their influence can appear to decline in later life. That is to say that mortality rates keep rising with advancing age, but they are less obviously influenced by any one cause for a given cohort of individuals. This effect occurs because the fatal consequences of a particular form of age-related dysfunction will tend to occur earlier in old age for individuals with the highest risk. With each passing year, a given age group is ever more made up of resilient survivors, people who - for whatever reason - do not have an overall mortality risk that is strongly determined by the specific dysfunction examined in the study. If they did, they would be dead already.
The age range over which this effect occurs is different depending on the risk factor in question and how it is linked to forms of harm. The cardiovascular risk factors examined here are more important or less important in a quite different set of ages in later life than, say, the advanced transthyretin amyloidosis that seems to be a majority cause of death for supercentenarians. The end of life is a set of overlapping curves of risk and influence for many different mechanisms, rising and falling out of lockstep due to the continued loss of those individuals most at risk, even as overall mortality rate rises inexorably.
Despite efforts during recent years to identify new risk factors or biomarkers that can predict cardiovascular diseases, no major breakthrough has been made in the clinical setting to beat the traditional risk factors that have been known for decades: blood pressure, diabetes mellitus, low-density lipoprotein (LDL)- and HDL, high-density lipoprotein (HDL)-cholesterol, smoking, and obesity. These traditional risk factors thus appear robust, and a deeper understanding of their usefulness is therefore desirable.
It is likely that the impact of a risk factor would decline by aging, given that there is a survival bias in the elderly: Many of those with high levels of risk factors at midlife would have experienced an event or died before being included in an investigation of risk factors in the elderly. And, indeed, the impact of a risk factor is usually lower than expected from studies in middle-aged samples when elderly populations are investigated. However, using this approach, it is hard to compare the strength of a risk factor in younger versus elderly subjects.
In order to study the impact of aging on the strengths of risk factors in a longitudinal fashion, we have, in the present study, used a sample of men all aged 50 years at a baseline examination in the early 1970s who has, so far, been followed for 4 decades. We tested the interactions between age and the traditional risk factors regarding incident cases of 3 major cardiovascular diseases: myocardial infarction, ischemic stroke, and heart failure, with the hypothesis that the strength of most, but not all, traditional risk factors would decline by aging. The major question to be answered was which of the risk factors that still retained an important impact in the elderly.
The present study showed, as expected, that most risk factors measured at middle age lost in power during the aging process regarding associations with incident cardiovascular disease. However, some exceptions from this general rule were noted: LDL-cholesterol was significantly related to incident myocardial infarction, whereas body mass index and fasting glucose were related to incident heart failure also in the elderly. The main reason for the general decline in the power of the risk factors over time is likely to be attributed to the fact that individuals with the highest values of the risk factors at midlife will experience an event at an early age, and therefore mainly low-risk individuals will remain at risk as the cohort becomes older. Thus, every cohort will consist of "survivors" when the follow-up increases, and in this group of survivors the impact of risk factors will be diminished.