Cardiovascular Disease Research

By Dr. Luis Vaschetto, Ph.D.Reviewed by Danielle Ellis, B.Sc.

Cardiovascular diseases are responsible for millions of deaths and hospitalizations worldwide each year, making them a significant public health concern and a major focus of research.

Initial studies on cardiovascular health

Jerry Morris initiated groundbreaking studies on cardiovascular health in 1949. He meticulously gathered occupational data for years before publishing his seminal findings in 1958. The causes, prevention, and treatment of all forms of cardiovascular disease remain active areas of biomedical research, with hundreds of studies published weekly in journals worldwide.

National Heart, Lung, and Blood Institute

The National Heart, Lung, and Blood Institute (NHLBI) is a leading organization dedicated to supporting cardiovascular research and promoting the prevention and treatment of heart, lung, and blood diseases. Through its research grants, the NHLBI seeks to elucidate the effects of heart diseases on men and women, assess the potential impact of risk factors, and develop effective prevention and treatment strategies. 

Clinical trials

Clinical trials are essential for evaluating novel approaches and thus preventing, diagnosing, and treating diseases and conditions. Volunteers are often recruited to participate in clinical trials focused on cardiovascular drugs and interventions. These trials investigate the safety and effectiveness of new medicines, medical devices, surgeries, or procedures before they are approved for widespread use.

The initial phases of clinical trials involve a small number of patients who willingly enroll in the study. These participants receive close monitoring and support from a team of healthcare providers who carefully assess the effects of the new medicine or procedure on their health. Even if a patient does not personally benefit from the trial's results, their participation contributes valuable information that can help others and advance scientific knowledge.

Informed consent

Upon volunteering for a clinical trial, patients undergo a thorough informed consent process. This involves a detailed explanation of the research, including its potential risks and benefits, presented in clear and understandable terms. Once the patient fully comprehends the study's implications and agrees to participate, they sign an informed consent form. It is important to note that patients retain the right to withdraw from the study at any time and for any reason.

Latest research

Recent advancements in cardiovascular research have shed light on the comparative effectiveness of different treatment strategies for patients with complex coronary artery blockages. The impact of lifestyle factors such as diet, exercise, aging, and hormones on the risk of heart disease is another fascinating area of research. Additionally, researchers are investigating the effects of mental health conditions like depression and stress on cardiovascular health. Another area of active investigation involves exploring the use of newer imaging and diagnostic techniques for the early and accurate detection of heart diseases.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially developed for treating diabetes, have emerged as a promising therapy for heart failure patients, even those without diabetes. These drugs have demonstrated remarkable efficacy in reducing cardiovascular risks, hospitalizations, and mortality in heart failure patients. Multiple large clinical trials have demonstrated the remarkable benefits of SGLT2 inhibitors in heart failure patients, showing their efficacy in reducing cardiovascular mortality, decreasing hospitalization rates, and improving quality of life.

The cardioprotective mechanisms of SGLT2 inhibitors include:

• Hemodynamic Effects: SGLT2 inhibitors promote diuresis and natriuresis (increased excretion of sodium), reducing blood volume and blood pressure. This decreased preload and afterload on the heart can improve cardiac function and reduce strain on the heart muscle.
• Metabolic Effects: SGLT2 inhibitors improve energy metabolism in the heart by shifting the heart's energy source from glucose to ketones, which are more efficient fuel sources. This metabolic shift reduces oxidative stress and improves cardiac efficiency.
• Anti-inflammatory Effects: SGLT2 inhibitors have been shown to reduce inflammation in the heart and blood vessels, which is a fundamental contributor to the progression of heart failure. This anti-inflammatory action may help protect against further heart damage and remodeling.

Genomics unlocks new frontiers in cardiovascular disease

Genomic research has made significant strides in recent years, leading to a deeper understanding of the genetic underpinnings of cardiovascular disease and paving the way for novel diagnostic, therapeutic, and preventive strategies. The most notable advances in cardiovascular genomics in the last few years are as follows:

• Polygenic Risk Scores (PRS): PRS have emerged as a promising tool for assessing an individual's genetic predisposition to cardiovascular disease. By analyzing thousands of genetic variants associated with cardiovascular disease risk, PRS can provide a more comprehensive risk assessment than traditional risk factors like family history or cholesterol levels.
• Genome-Wide Association Studies (GWAS): GWAS has identified numerous genetic variants associated with various forms of cardiovascular disease, including coronary artery disease, atrial fibrillation, and heart failure. These findings have shed light on the genetic architecture of cardiovascular disease and provided new targets for drug development.
• Targeted Therapies: Genetic insights have led to the development of targeted therapies for specific cardiovascular disease subtypes. For instance, PCSK9 inhibitors, which target a gene involved in cholesterol metabolism, have proven effective in lowering LDL cholesterol levels and reducing cardiovascular risk.
• Precision Medicine: Genomic information is increasingly being integrated into precision medicine approaches for cardiovascular disease. By tailoring treatment strategies based on an individual's genetic profile, clinicians can optimize drug selection, dosage, and preventive measures.
• Gene Editing: CRISPR-Cas9 gene editing technology holds promise for correcting genetic mutations that cause inherited forms of cardiovascular disease. While still in its early stages, gene editing has the potential to revolutionize the treatment of genetic heart diseases.
• Biomarker Discovery: Genomic studies have led to the discovery of novel biomarkers for cardiovascular disease diagnosis, prognosis, and treatment response. These biomarkers can aid in early detection, risk stratification, and personalized treatment decisions.

Information on clinical trials

Common sites that offer information on clinical trials include:

• www.clinicaltrials.gov
• https://www.nhlbi.nih.gov/
• http://clinicalresearch.nih.gov

Original Sources

1. https://www.womenshealth.gov/
2. ftp://ftp.cordis.europa.eu/pub/fp7/docs/cvd-fp6-booklet_en.pdf
3. https://www.ucop.edu/index.html
4. https://www.nhlbi.nih.gov/
5. https://assocham.org/
6. http://heartdisease.about.com/blresearch.htm

References

• Chatzopoulou, Fani, et al. "Dissecting miRNA–gene networks to map clinical utility roads of pharmacogenomics-guided therapeutic decisions in cardiovascular precision medicine." Cells 11.4 (2022): 607. https://pubmed.ncbi.nlm.nih.gov/35203258/
• Goodman, Matthew O., et al. "Pathway-specific Polygenic Risk Scores (PRS) identify OSA-related pathways differentially moderating genetic susceptibility to CAD." Circulation. Genomic and precision medicine 15.5 (2022): e003535. https://www.ahajournals.org/doi/10.1161/CIRCGEN.121.003535#:~:text=The%20effect%2Dmeasure%20modification%20of,the%20influence%20of%20OSA%20differently.
• Lemckert, Frances A., et al. "Lack of MG53 in human heart precludes utility as a biomarker of myocardial injury or endogenous cardioprotective factor." Cardiovascular research 110.2 (2016): 178-187. https://pubmed.ncbi.nlm.nih.gov/26790476/
• Mistry, Serena, and Deirdre Cocks Eschler. "Euglycemic diabetic ketoacidosis caused by SGLT2 inhibitors and a ketogenic diet: a case series and review of literature." AACE Clinical Case Reports 7.1 (2021): 17-19. https://pubmed.ncbi.nlm.nih.gov/33851013/
• Sano, Soichi, et al. "CRISPR-mediated gene editing to assess the roles of Tet2 and Dnmt3a in clonal hematopoiesis and cardiovascular disease." Circulation research 123.3 (2018): 335-341. https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.118.313225
• Scisciola, Lucia, et al. "Anti-inflammatory role of SGLT2 inhibitors as part of their anti-atherosclerotic activity: Data from basic science and clinical trials." Frontiers in Cardiovascular Medicine 9 (2022): 1008922. https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.118.313225
• Sluijter, Joost PG, et al. "Novel therapeutic strategies for cardioprotection." Pharmacology & therapeutics 144.1 (2014): 60-70. https://pubmed.ncbi.nlm.nih.gov/24837132/
• Tachmazidou, Ioanna, et al. "A rare functional cardioprotective APOC3 variant has risen in frequency in distinct population isolates." Nature communications 4.1 (2013): 2872. https://www.nature.com/articles/ncomms3872#:~:text=APOC3%20R19X%20constitutes%20to%20our,traits%20of%20high%20clinical%20relevance.
• Tentolouris, Anastasios, et al. "SGLT2 inhibitors: a review of their antidiabetic and cardioprotective effects." International journal of environmental research and public health 16.16 (2019): 2965. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720282/

Further Reading

• All Cardiovascular Disease Content
• What is Cardiovascular Disease?
• Cardiovascular Disease Diagnosis
• Lowering Risk for Cardiovascular Disease
• Causes and Symptoms of Hypoplastic Left Heart Syndrome