Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis

Abstract

Background: The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.

Methods: We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174374 deaths or major non-fatal vascular outcomes recorded among 1085949 people in 121 prospective studies.

Results: For people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.

Conclusion: Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.

Figure 1

Mean baseline height within 5-year age bands adjusted for calendar year (A) and differences in baseline height adjusted to age 50 years across calendar years relative to individuals born before 1910 (B). All analyses were adjusted for between-study differences in mean height via inclusion of a random intercept term in the multilevel mixed effects model. Error bars represent the 95% CI

Figure 2

HRs for coronary heart disease, stroke, cancer mortality and all-cause mortality across quantiles of baseline height values, among males and females. ^aIncludes both fatal and non-fatal events. Adjusted study-specific log_e HRs were combined by multivariate random-effects meta-analysis. Regression analyses were adjusted for age at baseline and smoking status (current smokers vs any other status), and stratified by decades of year of birth (<1920, 1920–29, 1930–39, 1940–49, 1950–59, ≥1960) and, where appropriate, by trial arm. Studies with <5 events of an outcome for each sex were excluded from the analysis of that particular outcome. Sizes of the data markers are proportional to the inverse of the variance of the log_e HRs. Reference groups are the fifth decile or third quintile in each plot

Figure 3

HRs for vascular outcomes per 1 SD (6.5 cm) higher baseline height, adjusted for age, sex, smoking and year of birth. ^aIncludes both fatal and non-fatal events. ^bRestricted to studies contributing to both outcomes. Causes of other vascular deaths are ordered by their strength of association. HRs were adjusted for age at baseline and smoking status (current smokers vs any other status), and stratified by decades of year of birth (<1920, 1920–29, 1930–39, 1940–49, 1950–59, ≥1960) and, where appropriate, by sex and trial arm. Studies with <5 events were excluded from the analysis of that particular outcome. For comparison with previous publications, HRs per 5 cm higher baseline height were 0.96 (0.94–0.97) for all vascular deaths; 0.94 (0.93–0.96) for coronary heart disease and 0.95 (0.93–0.97) for stroke

Figure 4

HRs for cause-specific non-vascular mortality per 1 SD (6.5 cm) higher baseline height, adjusted for age, sex, smoking and year of birth. With the exception of the classifications ‘Other/Unspecified’, causes of deaths are ordered by their strength of association. HRs were adjusted for age at baseline and smoking status (current smokers vs any other status), and stratified by decades of year of birth (<1920, 1920–29, 1930–39, 1940–49, 1950–59, ≥1960) and, where appropriate, by sex and trial arm. Studies with <5 events were excluded from the analysis of that particular outcome. HR for all-cause mortality per 1 SD (6.5 cm) height was 0.97 (0.96–0.99), I² = 69% (63–75%) and for unknown or ill-defined cause was 0.96 (0.93–1.00), I² = 45% (27–58%). For comparison with previous publications, HRs per 5 cm higher baseline height were 1.03 (1.02–1.04) for all cancer deaths and 0.94 (0.92–0.95) for all non-cancer non-vascular deaths