Results
The 29 cohort studies included 32 678 men and 25 931 women aged 65–74 years of whom, respectively, 3318 and 1480 died. Table 2 shows the characteristics of the included cohorts by sex.
For the cohort studies where the cause of death was known (n = 24), the proportion of deaths assigned to CVD was 40.7% for men and 33.3% for women, the corresponding proportions for cancer were 38.7% and 45.1% and for respiratory diseases, 6.8% and 4.0%.
In general, there was no substantial heterogeneity in the analyses regarding the combined WC–BMI categories resulting in an I < 17.5% (P > 0.22, for the chi-squared test) (Appendix 4, Figure 4.1, 4.2, available as Supplementary Data at IJE online). Similarly, no substantial heterogeneity was found in the continuous analyses (P > 0.05 for the chi-squared test from the random-effects model (Appendix 4, Table 4.1, available as Supplementary Data at IJE online).
Associations Between Combined WC–BMI Categories and Mortality
For men and women, a large WC (≥102 cm, men, and ≥88 cm, women) was associated with increased all-cause mortality RRs for those in the 'healthy' weight, overweight and obese BMI category compared with those classified as 'healthy' weight (20–24.9 kg/m) with a small WC (<94 cm, men and <80 cm, women) ( Table 3 ). Overall, we observed a tendency for lower all-cause and CVD mortality risks in the overweight category compared with the 'healthy' weight category within WC categories for both men and women (men: Pall-cause = 0.02, PCVD = 0.03; women: Pall-cause = 0.18, PCVD = 0.36), although the RR for overweight men with a small WC in the association with CVD mortality was higher compared with 'healthy' weight men with a small waist ( Table 3 ).
The risks of all-cause, CVD and cancer mortality were (although not statistically tested) higher for those with a large WC compared with those having a medium WC, except within the obese category in the association with all-cause and CVD mortality, and for women within the 'healthy' weight category in the association with cancer mortality ( Table 3 ).
Underweight was associated with highest all-cause mortality RRs in men {2.2 [95% confidence interval (CI): 1.8–2.8]} and women [2.3 (95% CI: 1.8–3.1)]. The RRs for cancer mortality were of the same magnitude. For CVD, an increased risk was found for men [RR = 2.9 (95% CI: 2.0–4.2)], but in women the RR was lower [RR = 1.5 (95% CI: 0.8–2.8)] ( Table 3 ).
Associations Between WC as a Continuous Variable and Mortality
All-cause Mortality We observed a J-shaped association between WC and all-cause mortality adjusted for age and smoking status (P < 0.01) with the lowest risk at 94 cm and 77 cm for men and women, respectively (Figure 1A). The cut-points of 102 cm in men and 88 cm in women were associated with all-cause mortality RRs of 1.03 (95% CI: 1.00–1.07) and 1.06 (95% CI: 0.97–1.15), respectively. An RR of 2.0 was associated with a WC of 132 cm in men and 116 cm in women (Figure 1A).
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Figure 1.
Relative risks of mortality from all causes (A), cardiovascular diseases (B), cancer (C) and respiratory disease (D) in men() and women() aged 65–74 years for WC as a continuous variable. All models were adjusted for age and smoking. In (A–D), solid lines indicate relative risks and dashed lines indicate 95% CIs. The black lines indicate the analyses unadjusted for BMI and the grey lines indicate the analyses with the adjustment for BMI. In this figure, for the analysis adjusted for BMI, a minimum of 94 cm was used, because there was no longer a parabolic association
Cause-specific Mortality Mortality from CVD, cancer and respiratory diseases were all associated with WC adjusted for age and smoking status in both men and women (P ≤ 0.03) (Figure 1B–D).
For CVD mortality, the lowest risk was at 89 cm and 63 cm for men and women, respectively. For men with a WC of 102 cm, the risk of CVD mortality was 1.11 (95% CI: 0.99–1.26) and for women with a WC of 88 cm this was 1.28 (95% CI: 0.92–1.77). An RR of 2.0 was associated with a WC of 123 cm in men and 105 cm in women (Figure 1B).
For cancer mortality, the lowest risk was at 73 cm and 74 cm for men and women, respectively. For men with a WC of 102 cm, the risk of cancer mortality was 1.13 (95% CI: 0.74–1.71) and for women with a WC of 88 cm this was 1.07 (95% CI: 0.90–1.27) (Figure 1C).
We observed a U-shaped relationship between WC and mortality from respiratory disease for both men and women. The lowest risk was at 104 cm for men and 99 cm for women. For men with a WC of 102 cm, the risk of mortality from respiratory diseases was 1.00 (95% CI: 0.98–1.03) and for women with a WC of 88 cm this was 1.15 (95% CI: 0.85–1.57) (Figure 1D).
Associations Between WC as a Continuous Variable and Mortality With Adjustment for BMI
After adjusting for BMI, WC remained associated with mortality from all causes, CVD and cancer in both sexes, and with respiratory diseases in men but not in women. The curves for CVD mortality were similar to those that were not adjusted for BMI (Pmen = 0.99; Pwomen = 0.62), but the curves for mortality from all causes (Pmen < 0.01; Pwomen < 0.01) and respiratory diseases (Pmen < 0.01; Pwomen = 0.40) were shifted to the left for both sexes, and for cancer only in women (P = 0.15). Thus, the lowest risks were at lower values of WC, and the RRs associated with a similar WC were higher after adjusting for BMI compared with the analyses unadjusted for BMI (Figures 1A–D). The curve of cancer mortality in men became linear after adjustment for BMI (Figure 1C).
Additional Analyses
We restricted our additional analyses to the four most relevant categories (i.e. underweight with a small WC, 'healthy' weight, overweight and obese combined with a large WC), because these categories gave the most consistent and strongest RRs in the main analyses.
The associations between the WC–BMI categories and all-cause and CVD mortality did not differ by age group (Appendix 2, Table 2.1, 2.2, available as Supplementary Data at IJE online). Excluding the first 2 years of follow-up, or major chronic diseases at baseline, or only including never smokers did not change the interpretation of our findings (Appendix 3, Table 3.1, Figure 3.1, available as Supplementary Data at IJE online).
We found some differences between the main analyses and additional analyses. After excluding the first 2 years of follow-up, we observed an RR of 1.6 (95% CI: 0.8–3.2) for CVD mortality risk in women with a 'healthy' weight and a large WC, compared with an RR of 2.2 (95% CI: 1.3–3.8) including all subjects. However, the additional analyses confirmed that for those with a large WC being in the 'healthy' weight category is associated with a higher RR (1.6) than the overweight category [RR = 1.3; (95% CI: 0.8–2.0)]. Furthermore, the analyses for continuous WC showed a similar pattern for all-cause mortality (Appendix 3, Table 3.1, Figure 3.1, available as Supplementary Data at IJE online).
After exclusion of major chronic diseases at baseline, the RR for CVD mortality in underweight men was 2.5 (95% CI: 0.8–7.7) compared with an RR of 3.3 (95% CI: 1.5–7.3) including all men, but still this confirms that underweight is associated with CVD mortality with an RR of at least 2.0 (Appendix 3, Table 3.1, Figure 3.1, available as Supplementary Data at IJE online).
Results for never smokers were comparable to the total population, except for the CVD mortality risks in men with a large WC and overweight/obesity, which were higher among never smoking men (RR = 2.2) than for the total population [RR = 1.3 (overweight + large WC]; RR = 1.5 (obesity + large WC)]. In women, the patterns of the curves for the continuous analyses of WC were similar, but in men the steepness of the curves differed. As a consequence, in never smoking men, higher WC levels were accompanied by lower RRs for all-cause mortality compared with the RRs in all men (Appendix 3, Table 3.1, Figure 3.1, available as Supplementary Data at IJE online).