A study led by researchers at Oxford Population Health has identified 12 key proteins linked to ischemic heart disease (IHD) that could be targeted by future drug treatments. The study is published in the Journal of the American College of Cardiology (JACC).
Heart disease or heart attack caused by blockage of the coronary arteries, known as IHD, is a leading cause of death worldwide, accounting for about 9 million deaths annually. East Asia, particularly China, has witnessed some of the largest increases in IHD prevalence and deaths in recent decades, highlighting the need for improved treatment and prevention strategies.
Proteins play a crucial role in regulating the cardiovascular system by controlling blood lipids (fatty substances in the bloodstream, including low-density lipoprotein cholesterol [LDL-C]), chronic inflammation and blood pressure, making them targets for new drugs to treat IHD.
The researchers used advanced tools called high throughput assays (using both Olink and SomaScan platforms) to measure levels of 9,500 proteins in blood samples collected at enrolment of 1,976 participants in the China Kadoorie Biobank (CKB) who subsequently developed IHD. They compared them with samples from 2,001 participants who remained free of IHD during follow-up. They then used advanced genetic analyses to examine the likely causal associations of these proteins with IHD risk.
The CKB study, jointly coordinated by Oxford Population Health (UK) and Peking University (China), recruited 512,000 adults from 10 diverse areas of China between 2004 and 2008.
Among 12 proteins identified as likely to be linked with IHD, eight were lipid-related, another was hypertension-related, and three other proteins were related to chronic inflammation, which plays a lesser-known role in conditions that cause heart attack and stroke.
Chronic inflammation in the walls of the arteries supplying the heart occurs in response to damage to the inner lining of the artery walls caused by higher levels of blood pressure or cholesterol. Ongoing inflammation results in blockage of the coronary arteries and reduced blood flow to the heart.
While statin treatment is highly effective at lowering blood levels of cholesterol and the risk of heart attacks and stroke, the study findings suggest that combinations of drugs which target lipids such as LDL-C and inflammation simultaneously should be prioritised for development and evaluation in clinical trials.
Professor Robert Clarke, Emeritus Professor at Oxford Population Health, and joint senior author of the paper said:
The findings provide support for evaluation of new drugs to lower blood levels of both lipids and inflammation for improved treatment of IHD, beyond statin therapy.
The researchers performed identical analyses for similar proteins in blood samples from people of European ancestry and reported similar, albeit not identical results for certain protein biomarkers, highlighting the need for further studies involving multiple ancestries to better understand the genetic architecture of proteins in diverse populations.
The researchers also compared their findings with those reported in previous studies that used less robust analytic approaches and identified a number of weaknesses, including a lack of replication in different populations.
Professor Zhengming Chen, Principal Investigator for CKB in the UK and a senior author of the study, commented:
The results highlight the importance of replicating associations of proteins with IHD in independent populations and the need to develop robust analytic frameworks to ensure the reliability of study findings.