Cardiovascular risk factors and lifestyle behaviours in relation to longevity: a Mendelian randomization study

Abstract

Background The American Heart Association introduced the Life's Simple 7 initiative to improve cardiovascular health by modifying cardiovascular risk factors and lifestyle behaviours. It is unclear whether these risk factors are causally associated with longevity. Objectives This study aimed to investigate causal associations of Life's Simple 7 modifiable risk factors, as well as sleep and education, with longevity using the two‐sample Mendelian randomization design. Methods Instrumental variables for the modifiable risk factors were obtained from large‐scale genome‐wide association studies. Data on longevity beyond the 90th survival percentile were extracted from a genome‐wide association meta‐analysis with 11,262 cases and 25,483 controls whose age at death or last contact was ≤ the 60th survival percentile. Results Risk factors associated with a lower odds of longevity included the following: genetic liability to type 2 diabetes (OR 0.88; 95% CI: 0.84;0.92), genetically predicted systolic and diastolic blood pressure (per 1‐mmHg increase: 0.96; 0.94;0.97 and 0.95; 0.93;0.97), body mass index (per 1‐SD increase: 0.80; 0.74;0.86), low‐density lipoprotein cholesterol (per 1‐SD increase: 0.75; 0.65;0.86) and smoking initiation (0.75; 0.66;0.85). Genetically increased high‐density lipoprotein cholesterol (per 1‐SD increase: 1.23; 1.08;1.41) and educational level (per 1‐SD increase: 1.64; 1.45;1.86) were associated with a higher odds of longevity. Fasting glucose and other lifestyle factors were not significantly associated with longevity. Conclusion Most of the Life's Simple 7 modifiable risk factors are causally related to longevity. Prevention strategies should focus on modifying these risk factors and reducing education inequalities to improve cardiovascular health and longevity.

Physical Activity and Risks of Cardiovascular Diseases: A Mendelian Randomization Study

“…Mendelian randomization (MR) is an alternative epidemiological approach that can use genetic variations as instrumental variables (IVs) to uncover the causal relationship between exposure and disease outcomes, and avoiding potential confounders in observational studies ( 15 ). MR has been previously used to explore the association of several risk factors and CVDs, such as smoking ( 16 ), body mass index (BMI) ( 17 ), and alcohol consumption ( 18 ). In this study, a two-sample MR study was performed to examine the potential causal association between physical activity and risk of CVDs using genetic variations associated with self-reported and objective accelerometer-based physical activity identified from published genome-wide association studies (GWASs).…”

Does exercise prevent major non‐communicable diseases and premature mortality? A critical review based on results from randomized controlled trials

“…The lack of established causality between physical activity and CVD is further shown by mendelian randomization (MR) studies that have not been able to establish an association between genetically predicted accelerometer‐measured physical activity and the risk of heart failure, coronary heart disease, myocardial infarction, and stroke [81, 82]. Another MR study found that whereas genetic predisposition to a variety of metabolic risk factors and smoking were associated with lower odds of longevity, there was no such association for genetically predicted self‐reported physical activity [83]. Furthermore, although one twin study has found a single estimate of self‐reported physical activity to be associated with reduced risk of all‐cause and cardiovascular mortality in monozygotic twin pairs with discordant levels of physical activity [84], several other twin studies have shown other results.…”

Alcohol consumption in relation to cardiovascular diseases and mortality: a systematic review of Mendelian randomization studies

“…After full-text screening, 23 studies were included in the current systematic review . Citation tracking resulted in one additional publication [53]. The 24 included studies were published between 2008 and 2020.…”