Saving a Million Hearts: One Heart at a Time!

March 12, 2018 by Muin J. Khoury, Office of Public Health Genomics, Centers for Disease Control and Prevention and George A. Mensah, Center for Translation Research and Implementation Science, National Heart, Lung and Blood Institute

Million Hearts®[PDF 1.40 MB] led to the prevention of more than 100 thousand cardiovascular (CVD) events in the first two years and is projected to have prevented half a million CVD events by 2019.

Cardiovascular disease (CVD), principally ischemic heart disease and stroke, remains the leading cause of U.S. deaths for men and women and all races and ethnicities in spite of major progress in its prevention and treatment. CVD is also the greatest contributor to racial disparities in life expectancy. In 2012, 120 public and private partners and 20 federal agencies launched the Million Hearts®initiative to prevent one million heart attacks and strokes by 2017. The initiative sought to implement proven, effective, and inexpensive interventions in both clinical and community settings. In healthcare, the initiative helped improve management of the ABCS (aspirin use for high risk patients, blood pressure control, cholesterol management, and smoking cessation). In population settings, it helped enhance efforts to reduce smoking prevalence and sodium consumption and eliminate artificial trans fat from the food supply. A key approach of Million Hearts® is to engage many stakeholders, including clinicians, pharmacists, insurers, health-care systems, retailers, consumer groups, and others.

The initiative successfully aligned national CVD prevention efforts around a few evidence-based interventions and strategies. Million Hearts® partners contributed to the prevention of more than 100 thousand cardiovascular events in the first two years and is projected to have prevented up to half a million CVD events when the final results are known in 2019. A 2018 CDC Public Health Grand Round highlighted the impact and ongoing priorities of Million Hearts®. Specifically, Million Hearts 2022[PDF 81.1 KB] will add new areas such as physical activity, cardiac rehabilitation, and an intense focus on high-burden “priority” populations.

The initiative also illustrated challenges in the implementation of large multifaceted multi-stakeholder collaborations in the face of changing health policy, clinical practice, as well as emerging new evidence from ongoing scientific advances. Chief among these advances is the field of genomics and precision medicine.

In our 2011 blog, “A million hearts, a thousand genes and your family history,” we wondered what the emerging tools of genomics can do to help reduce the burden of heart disease and stroke. We discussed the importance of knowledge of family history as a risk factor for CVD and the need to diagnose and reduce disease and death in people with the 50 or more genetic conditions associated with CVD.

But, much has happened in genomics and precision medicine since 2011. Major advances are occurring in genomics and related fields for a wide variety of common diseases, most notably cancer, but also CVD . Increasingly, whole genome sequencing is being used with other analytic measures (DNA methylation, RNA expression, metabolite profiles) in large-scale collaborative initiatives. The national precision medicine effort, All of US Research Program , seeks to recruit at least a million people and follow them over time. The Trans Omics Precision Medicine (TOPMed ) research program is a major CVD-related initiative sponsored by the National Heart, Lung, and Blood Institute . The program collects whole-genome sequence and other -omics data (In biology, -omics refers to measurable differences or changes in biological molecules, such as genes, metabolites, proteins, and RNA.) in large cohorts to generate scientific resources and evidence to accelerate advances in precision medicine.

New tools will help develop individualized approaches to CVD

We are still in the early days of genomics and precision medicine; but there are current scientific applications that, if implemented, might contribute to reducing the burden of CVD in the United States. Since 2015, the CDC has developed and continuously updated the Public Health Genomics Knowledge Base (PHGKB), which tracks the scientific literature on translation and evaluation research in the field, evidence-based guidelines, and implementation science to drive practice and population health outcomes. We also developed a simple evidence-based three-tier classification system to help prioritize genomic applications for clinical practice and translational research. A quick review of PHGKB reveals the progress made in population genomics and CVD. As of February 20, 2018, there were 21 guidelines, 48 evidence synthesis papers, and 200 translation and implementation studies relevant to heart disease and genomics. In addition, there were four guidelines, 14 evidence-synthesis papers and 36 translation and implementation studies relevant to stroke.

While the field still lags behind cancer precision medicine, there are current opportunities to use genomics now and in the near future to reduce the CVD burden.

Reducing the population burden of Familial Hypercholesterolemia

There are more than a million people in the United States with Familial Hypercholesterolemia (FH), an autosomal dominant, relatively common genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C) levels and accelerated atherosclerotic cardiovascular disease . Persons with FH have a risk of ASCVD that is 2.5-10 fold that of the general population. But when FH is diagnosed and treated early in life, the risk is reduced by ~80%. However, the majority of persons with FH have never been diagnosed or treated effectively . Active case finding of FH followed by family-based cascade screening has the potential to identify many additional individuals with FH and help ensure treatment to prevent heart disease. Recent data show disparities in recognition and management of the condition among racial and ethnic minority groups and among women. These disparities contribute to under treatment of FH patients in the United States.

Promising CVD-related genomic applications

There are other CVD-related genetic conditions that can be diagnosed and appropriately managed using new genomic sequencing technologies that are now recommended in the American College of Medical Genetics and Genomics return of results for genome sequencing studies. These include hypertrophic cardiomyopathy, long QT syndrome, Marfan syndrome, Brugada syndrome, and others. Another example of recent genomic breakthrough in CVD is the finding that people with mutations in the PCSK9 gene are at a much lower risk for heart attacks, which has led to the development of a novel antibody therapy targeting the PCSK9 protein —an important success story in CVD genomics.

Numerous pharmacogenetic variants that are prevalent in the population have the potential to improve clinical management and outcomes of several commonly-used CVD drugs (e.g., clopidogrel, warfarin, and statins). Collaborative groups such as the Pharmacogenomics KnowledgeBase (PharmGKB) evaluate emerging evidence of pharmacogenomics and publish recommendations to inform clinical practice. As of February 20, 2018, PharmGKB has information on 100 dosing guidelines, on 636 drugs related to 129 drug pathways, and 498 drug labels. There is also mounting knowledge that the additive effects on the risk for many diseases of numerous genetic variants can be quantified using polygenic or genetic risk scores (GRSs). GRSs have been developed for various common diseases such as type 2 diabetes, hypertension, coronary heart disease, and several cancers.

How to use GRS for genetic risk stratification to help target screening, prevention, and treatment is now the subject of scientific studies . For example, in the context of coronary heart disease, a recent study showed GRS can identify 2.5% of all individuals in the population with a four-fold increased risk for coronary disease that is similar to disease risk associated with familial hypercholesterolemia. The implications of these findings for treatment of high risk people to reduce the burden of CVD will need further investigation.

What’s next?

Over the next five years, Million Hearts® plans to continue engaging partners nationwide to improve CV health and care for all Americans. Its priorities will include optimizing care to improve ABCS; using public health efforts to promote healthy levels of sodium consumption, increased physical activity, and decreased tobacco use; and helping to improve outcomes for populations with an especially high burden of disease. At the same time, new discoveries from the world of genomics and precision medicine will continue to emerge. Promising applications should be pursued with translation research and implementation science to make an impact on CVD morbidity and mortality.

In the long run, we expect that genomic insights into disease mechanisms, and new screening and treatment, based on risk stratification will complement current approaches and push the cardiovascular field into personalized interventions to help save millions of hearts, one heart at a time!