McCarron et al. Respond to "Height-Cardiovascular Disease Relation": Are All Risk Factors Equal?

Peter McCarron1, Mona Okasha2, James McEwen3 and George Davey Smith2

1 Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD.
2 Department of Social Medicine, University of Bristol, Bristol, United Kingdom.
3 Department of Public Health, University of Glasgow, Glasgow, United Kingdom.


    INTRODUCTION
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We thank Miura et al. (1Go) for their thoughtful commentary on our paper. In their article they outline three major approaches to reducing the burden of cardiovascular disease: continuing to address traditional risk factors in adults; tackling these factors in early life; and improving understanding of the role of early life factors in the etiology of cardiovascular disease so that further appropriate preventive interventions can be designed. We are in broad agreement with their views and wish to expand on some of the issues raised.

Our findings demonstrate that, after controlling for several important confounding variables, greater height in young adult males is associated with lower cardiovascular disease mortality (2Go). Although the analyses were restricted to White males and there were no data on blood lipids, these weaknesses are unlikely to severely limit the overall generalizability of the results. Importantly, since the participants would largely have shared affluent adulthood socioeconomic circumstances (3Go), the role of socioeconomic confounding is greatly reduced. In addition, as height was measured in early adult life, height-disease associations cannot be due to any shrinkage secondary to chronic disease. The findings point convincingly to the role of childhood factors in the etiology of cardiovascular disease.

Are such findings important? Miura et al. state that there is already enough knowledge to reduce the cardiovascular disease burden, and they rightly emphasize the need to appropriately alter smoking, dietary, and exercise patterns in both adults and, as is being increasingly recognized, younger persons. Evidence from several major studies conducted over the last 20 years demonstrates that cardiovascular disease risk factors, including high blood pressure (4Go), obesity (5Go), adverse lipid profile (6Go), and glucose intolerance (7Go), are evident in young persons. These risk factors cluster (8Go), track into adulthood (9Go, 10Go), and ultimately result in increased rates of cardiovascular disease (11Go, 12Go).

Success in tackling traditional cardiovascular disease risk factors in youth should result in further reductions in cardiovascular disease in adulthood, although the successful implementation of preventive interventions is challenging (13GoGo–15Go). Furthermore, even if adequately tackled, it must be acknowledged that, while the major known risk factors appear to explain the distribution of cardiovascular disease, its etiology is still not fully understood. We cannot adequately account for the distribution of hypertension, insulin resistance, or blood lipids; these factors themselves need explaining. In addition, while the conventional risk factors may account for population differences in cardiovascular disease, the prediction of individual risk remains uncertain. Finally, other, more recently identified, risk factors may be important. There are significant distinctions between traditional risk factors, such as smoking, circulating cholesterol, high blood pressure, and insulin resistance on the one hand, and more novel risk factors, such as height, birth weight, and fibrinogen on the other. The former group of risk factors both relate to cardiovascular disease risk within persons and can largely account for important differences in cardiovascular disease risk between populations and for temporal trends in cardiovascular disease risk within populations (16Go), especially if the importance of lag periods is fully considered (17GoGo–19Go). The latter factors are consistently associated with cardiovascular disease risk at the individual level, but their distribution is not consistent with population differences. Although cardiovascular disease rates are lower in the developing world than in the developed world, the mean birth weight (20Go) and adult stature (21Go) are lower, and fibrinogen is often higher (22Go) than in the more affluent countries.

There are three possible (and not mutually exclusive) explanations for the incoherence of individual-level and between-population risk associations with respect to these factors. First, these factors may be contingent—but not necessary or causal—correlates of other causal factors. Second, they may be causally related to cardiovascular disease, but they may also correlate with other major risk factors across populations in such a way that their influence is cancelled out (as height or birth weight might correlate positively with plasma cholesterol across populations). Third, they may act only in interaction with other factors; for example, low birth weight or short stature might increase cardiovascular disease risk only in the presence of a diet that generates high cholesterol levels and obesity (23Go). Clearly an important distinction must be made between those factors that coherently explain both within-individual and between-population differences in disease risk and those that do not.

Cohort studies examining the early life origins of conventional cardiovascular disease risk factors and cardiovascular disease risk itself may still play a fruitful role. Studies of children in Bogalusa, Louisiana (8Go, 24Go), and of pregnant women and their babies in Bristol, England (5Go, 25Go), have yielded insights into the etiology of cardiovascular disease. Such large studies are certainly expensive, but they have produced important results in relatively short periods of time. Continued follow-up and development of new cohorts will contribute to better understanding of cardiovascular disease through investigation of new etiologic hypotheses. Several hypotheses relating to height are outlined by Miura et al. Overarching issues, such as whether there are critical periods for adverse exposures and the importance of gene-environment interactions, can also be examined. Importantly, because of the age of the persons in these studies, they may help to identify early interventions that prevent the occurrence of irreversible pathologic changes. The growing body of research that convincingly suggests that the health of future generations is related to the health of today's children—tomorrow's parents—may have more impact than yet more studies on interventions among middle-aged persons. Efforts to prevent cardiovascular disease in today's children are, in turn, likely to benefit the cardiovascular health of persons who are not yet conceived. Ensuring that this goal is achieved should be a major part of the answer to the timely question of Miura et al.: Where to go from here?


    NOTES
 
Correspondence to Dr. Peter McCarron, N. Ireland Cancer Registry, Department of Epidemiology and Public Health, The Queen's University of Belfast, Mulhouse Building, Grosvenor Road, Belfast BT12 6BJ, United Kingdom (e-mail: mccarrop{at}mail.nih.gov).


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Received for publication December 3, 2001. Accepted for publication December 5, 2001.


Related articles in Am. J. Epidemiol.:

Height in Young Adulthood and Risk of Death from Cardiorespiratory Disease: A Prospective Study of Male Former Students of Glasgow University, Scotland
Peter McCarron, Mona Okasha, James McEwen, and George Davey Smith
Am. J. Epidemiol. 2002 155: 683-687. [Abstract] [FREE Full Text]