Lifestyle changes can greatly reduce heart disease risk in people with high genetic risk

A recent study published in the journal Nature Human Behavior explored the interactions between genetic risk and lifestyle factors on the onset and types of cardiovascular disease (CVD).

The research revealed that individuals with unfavorable lifestyles and high genetic risk are more likely to experience early-onset CVD. Importantly, the study found that lifestyle improvements can significantly reduce the incidence of CVD, particularly among young adults with high genetic risk.

Study: Joint impact of polygenic risk score and lifestyles on early- and late-onset cardiovascular diseases. Image Credit: Chinnapong / Shutterstock

Background

Over recent decades, while CVD rates have stabilized or decreased in adults over 50, they have risen among individuals between 15 and 49, highlighting the growing concern about early-onset cardiovascular illness. Both environmental and genetic variables contribute to this risk.

Polygenic risk scores (PRS) calculated using genome-wide association studies (GWAS) can help predict an individual’s genetic predisposition to diseases like coronary artery disease (CAD), especially in European populations.

However, PRSs have shown limited success in predicting CVD in East Asian populations or other forms of CVD like stroke. Additionally, few studies have developed PRSs for intracerebral hemorrhage (ICH) in the Chinese population.

The interaction between genetic risk and lifestyle factors on CVD risk, particularly the difference between early- and late-onset CVD, remains underexplored.

About the study

This study aimed to bridge these research gaps by evaluating the combined effects of lifestyle factors and genetic risk on CVD outcomes through a long-term study of adults in China.

The study involved participants from the China Kadoorie Biobank, an ongoing prospective cohort study that enrolled over half a million adults aged 30 to 79 from urban and rural areas in China.

From this large group, 100,639 participants were selected for genetic analysis, focusing on cardiovascular diseases (CVDs). The researchers excluded anyone with a history of heart attack or stroke at the start, leaving 96,400 participants for analysis.

Through surveys and physical exams, participants provided information on their lifestyles, including education, marital status, smoking habits, diet, physical activity, body mass index (BMI), and waist circumference.

They were then categorized into three groups based on the healthiness of their lifestyles: favorable, intermediate, and unfavorable. The study tracked health outcomes by linking to national health records and local registries. Key outcomes were coronary artery disease (CAD), ischemic stroke (IS), and intracerebral hemorrhage (ICH).

Genetic risk scores were created using data from other studies and statistical models. Participants were classified into low, intermediate, and high genetic risk groups. Various statistical methods were employed to assess the relationship between genetic risk, lifestyle factors, and the onset of CVDs. Sensitivity analyses were conducted to ensure the robustness of the findings.

Findings

The study found that individuals with unfavorable lifestyles and high genetic risk developed ICH, CAD, and IS earlier than those with favorable lifestyles and low genetic risk. Specifically, high-risk individuals experienced these conditions 1.6, 3.4, and 6.0 years earlier on average, respectively.

When comparing those with high genetic risk and unfavorable lifestyles to those with low risk and favorable lifestyles, the hazard ratios (HRs) for early-onset ICH, CAD, and IS were 6.53, 6.62, and 3.34, respectively. For late-onset outcomes, the HRs were 3.55 for ICH, 6.47 for CAD, and 2.31 for IS.

The study showed no significant interaction between lifestyle factors and genetic risk on a multiplicative scale. However, there were positive interactions on an additive scale, meaning that the combined effect of an unfavorable lifestyle and high genetic risk significantly increased CVD risk. Changing from an unfavorable to a favorable lifestyle led to a 14.7-fold greater reduction in early-onset CAD incidence for high-risk individuals compared to low-risk individuals, and similar benefits were seen for IS and late-onset CAD. This suggests that lifestyle improvements can substantially reduce CVD risk, particularly in those with a high genetic predisposition.

Conclusions

In this extensive study involving over 100,000 Chinese adults, researchers assessed the genetic predisposition to cardiovascular diseases (CVD) and how lifestyle factors interact with these risks.

They found that both high genetic risk and unhealthy lifestyles were strongly linked to an earlier onset of CVD. The combination of high genetic risk and poor lifestyle significantly increased the risk of early-onset coronary artery disease (CAD) and ischemic stroke (IS), while late-onset CAD was also affected.

Previous studies conducted primarily in European populations showed similar patterns, but this research uniquely focused on a Chinese cohort.

The study’s strengths include its large sample size, diverse genetic data, and long follow-up period. However, there were limitations such as the low incidence of CVD in young adults and potential inaccuracies in self-reported lifestyle data.

Future research should consider analyzing sex-specific data and updating lifestyle information over time to improve accuracy. This study underscores the importance of genetic testing and lifestyle modifications, particularly for young adults with high genetic risk, as a strategy for precision prevention of CVD.