Reverse Epidemiology of Traditional Cardiovascular Risk Factors in the Geriatric Population

Abstract

Traditional risk factors of cardiovascular death in the general population, including body mass index (BMI), serum cholesterol, and blood pressure (BP), are also found to relate to outcomes in the geriatric population, but in an opposite direction. Some degrees of elevated BMI, serum cholesterols, and BP are reportedly associated with lower, instead of higher, risk of death among the elderly. This phenomenon is termed "reverse epidemiology" or "risk factor paradox" (such as obesity paradox) and is also observed in a variety of chronic disease states such as end-stage renal disease requiring dialysis, chronic heart failure, rheumatoid arthritis, and AIDS. Several possible causes are hypothesized to explain this risk factor reversal: competing short-term and long-term killers, improved hemodynamic stability in the obese, adipokine protection against tumor necrosis factor-α, lipoprotein protection against endotoxins, and lipophilic toxin sequestration by the adipose tissue. It is possible that the current thresholds for intervention and goal levels for such traditional risk factors as BMI, serum cholesterol, and BP derived based on younger populations do not apply to the elderly, and that new levels for such risk factors should be developed for the elderly population. Reverse epidemiology of conventional cardiovascular risk factors may have a bearing on the management of the geriatric population, thus it deserves further attention.

Keywords: Reverse epidemiology; cardiovascular risk factors; mortality; obesity paradox; risk factor paradox.

Figure 1

The association of obesity (BMI≥30) with mortality association weakens with increasing age and it becomes non-significant after the age of 75. HR: Hazard Ratio. From a meta-analysis of 20 cohort studies (total n: 4,664,198) by Wang et al , with permission.* * Pending obtaining permission

Figure 2

In the geriatric population, the optimal BMI associated with minimum risk of death shifts towards overweight/obesity. HR: Hazard Ratio. From a meta-analysis of 32 cohort studies (total n: 197,940) by Winter et al , with permission. * * Pending obtaining permission

Figure 3

In the general population, waist circumference (WC) values >102 cm in males or > 88 cm in females are considered “high risk”. In the geriatric population, however, WC values associated with the lowest risk of death are reportedly close to these “high risk” thresholds (black lines). Nevertheless, the optimal WC values are decreased with adjustment for BMI (grey lines). RR: Relative Risk. Solid and dashed lines, respectively, illustrate RR values and their 95% confidence intervals. From a meta-analysis of 29 cohort studies (total n: 58,609) of elderly individuals by de Hollander et al , with permission. * * Pending obtaining permission

Figure 4

Aging alters the association of total cholesterol (TC), non-high-density lipoprotein (non-HDL) cholesterol, and HDL cholesterol with cardiovascular and non-cardiovascular mortality. Hazard ratios (HR) are calculated per 1 mmol/l (=38.6 mg/dl) increase. From a study of 5,750 Rotterdam Cohort participants by Newson et al , with permission. * * Pending obtaining permission

Figure 5

Among the elderly, higher total cholesterol is reportedly associated with better survival. From a cohort study of 4,128 adults aged ≥70 years by Volpato et al , with permission. * * Pending obtaining permission.* * Pending obtaining permission

Figure 6

The protective effects of lower systolic or diastolic blood pressure against vascular mortality attenuates with increasing age depicted by hazard ratios getting closer to one (null effect) in consecutive decades. IHD: Ischemic Heart Disease. From a meta-analysis of 61 studies (total n: 1 million) by Lewington et al , with permission. * * Pending obtaining permission

Figure 7

Higher systolic or diastolic blood pressure (SBP or DBP) is associated with better survival within non-hypertensive range (SBP <140 or DBP <90, respectively) and it is not associated with any significantly different mortality within hypertensive range (SBP ≥140 or DBP ≥90). The box plots illustrate median, interquartile range, and total range of survival for each SBP or DBP class. From a cohort study of 4,071 individuals aged ≥80 years by Oates et al , with permission. * * Pending obtaining permission