Variations in the association of height with mortality, cardiovascular disease and cancer in low-, middle- and high-income countries
Authors: Khetan Aditya K , Leong Darryl P , Gupta Rajeev , Zhu Yibing , Li Sidong , Liu Weida , Kruger Iolanthé M , Teo Koon K , Wielgosz Andreas , Yusuf Rita , Noor Khan Nor-Ashikin Mohamed , Khatib Rasha , Alhabib Khalid F , Karsidag Kubilay , Chifamba Jephat , Mohammadifard Noushin , Serón Pamela , Lopez-Jaramillo Patricio , Orlandini Andres , Szuba Andrzej , Yusufali Afzalhussein , Nair Sanjeev , Rosengren Annika , Yeates Karen , Dans Antonio Miguel , Iqbal Romaina , Avezum Álvaro , Rangarajan Sumathy , Yusuf Salim 
Published: December 2021

Abstract

Background
Final adult height is a useful proxy measure of childhood nutrition and disease burden. Tall stature has been previously associated with decreased risk of all-cause mortality, decreased risk of major cardiovascular events and an increased risk of cancer. However, these associations have primarily been derived from people of European and East Asian backgrounds, and there are sparse data from other regions of the world.

Methods
The Prospective Urban-Rural Epidemiology study is a large, longitudinal population study done in 21 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35–70 years. Height was measured in a standardized manner, without shoes, to the nearest 0.1 cm. During a median follow-up of 10.1 years (interquartile range 8.3–12.0), we assessed the risk of all-cause mortality, major cardiovascular events and cancer.

Results
A total of 154 610 participants, enrolled since January 2003, with known height and vital status, were included in this analysis. Follow-up event data until March 2021 were used; 11 487 (7.4%) participants died, whereas 9291 (6.0%) participants had a major cardiovascular event and 5873 (3.8%) participants had a new diagnosis of cancer. After adjustment, taller individuals had lower hazards of all-cause mortality [hazard ratio (HR) per 10-cm increase in height 0.93, 95% confidence interval (CI) 0.90–0.96] and major cardiovascular events (HR 0.97, 95% CI 0.94–1.00), whereas the hazard of cancer was higher in taller participants (HR 1.23, 95% CI 1.18–1.28). The interaction p-values between height and country-income level for all three outcomes were &lt;0.001, suggesting that the association with height varied by country-income level for these outcomes. In low-income countries, height was inversely associated with all-cause mortality (HR 0.88, 95% CI 0.84–0.92) and major cardiovascular events (HR 0.87, 95% CI 0.82–0.93). There was no association of height with these outcomes in middle- and high-income countries. The respective HRs for cancer in low-, middle- and high-income countries were 1.14 (95% CI 0.99–1.32), 1.12 (95% CI 1.04–1.22) and 1.20 (95% CI 1.14–1.26).

Conclusions
Unlike high- and middle-income countries, tall stature has a strong inverse association with all-cause mortality and major cardiovascular events in low-income countries. Improved childhood physical development and advances in population-wide cardiovascular treatments in high- and middle-income countries may contribute to this gap. From a life-course perspective, we hypothesize that optimizing maternal and child health in low-income countries may improve rates of premature mortality and cardiovascular events in these countries, at a population level.