Personalizing treatments for patients based on cardiovascular phenotyping

Abstract

Introduction: Cardiovascular disease persists as the leading cause of death worldwide despite continued advances in diagnostics and therapeutics. Our current approach to patients with cardiovascular disease is rooted in reductionism, which presupposes that all patients share a similar phenotype and will respond the same to therapy; however, this is unlikely as cardiovascular diseases exhibit complex heterogeneous phenotypes.

Areas covered: With the advent of high-throughput platforms for omics testing, phenotyping cardiovascular diseases has advanced to incorporate large-scale molecular data with classical history, physical examination, and laboratory results. Findings from genomics, proteomics, and metabolomics profiling have been used to define more precise cardiovascular phenotypes and predict adverse outcomes in population-based and disease-specific patient cohorts. These molecular data have also been utilized to inform drug efficacy based on a patient's unique phenotype.

Expert opinion: Multiscale phenotyping of cardiovascular disease has revealed diversity among patients that can be used to personalize pharmacotherapies and predict outcomes. Nonetheless, precision phenotyping for cardiovascular disease remains a nascent field that has not yet translated into widespread clinical practice despite its many potential advantages for patient care. Future endeavors that demonstrate improved pharmacotherapeutic responses and associated reduction in adverse events will facilitate mainstream adoption of precision cardiovascular phenotyping.

Keywords: cardiovascular disease; drug repurposing; genomics; metabolomics; phenotyping; precision medicine; proteomics.

Figure 1.. Reductionism in cardiovascular medicine.

Reductionism in medicine assumes that all patients who have the same symptoms and exam findings are similar despite the fact that there is heterogeneity among individuals (left). These patients undergo clinical testing to phenotype their disease (center). The results of laboratory and functional testing identifies the cardiovascular phenotype and associated medical or interventional therapies (right).

Figure 2.. The effect of exposures on genetic risk.

Low, intermediate, or high genetic risk was determined for individuals based on a risk score that included 50 variants and the effect of lifestyle behaviors (diet, weight, tobacco use, and exercise) on genetic risk was determined. Adapted from (20).

Figure 3.. Pharmaco-omics and precision cardiovascular phenotyping for pharmacotherapeutic selection.

Precision cardiovascular phenotyping recognizes that patients with similar clinical signs and symptoms have significant heterogeneity. By utilizing molecular omics and in-depth clinical data to create a comprehensive cardiovascular phenotype, personalized therapeutics can be selected.

Figure 4.. Challenges to address to facilitate routine precision cardiovascular phenotyping.

Several challenges to be addressed before precision cardiovascular phenotyping for personalized therapeutic selection becomes mainstream. These challenges are broadly related to molecular profiling and omics, data management and analysis, and acceptance by stakeholders.