by Harold L. Kennedy, MD

 Key takeaways: 

• Risk factors for development of comorbidities include a variety of blood/chemical biomarkers and genetic markers.
• For heart disease, multiple gene variants disclosed a prevalence of 1.2% of arrhythmogenic right ventricular dysplasia, 2.6% of hypertrophic cardiomyopathy and 3.1% of diabetic cardiomyopathy in this population.
• Most people at risk for adverse outcomes are still identified via the time-proven, age-old practice of a thorough history and physical examination.

Comorbidities are classically defined as “a condition existing simultaneously with and usually independently of another medical condition.” It is recognized today that many comorbidities can be insidious and asymptomatic (e.g., hypertension, atherosclerosis or genetic variants) or known and recognized from a symptomatic illness (e.g., pneumonia or influenza). 

Risk factors took their genesis initially from family hereditary histories of a patient’s parents and relatives, indicating to a patient their possible risk of loss of health. The concept of health risk then evolved further with the seminal Framingham study which added the science and identity of blood biomarkers (e.g.., hypercholesterolemia) indicating future risk of atherosclerotic disease.

This evolution of medical knowledge of “risk factors” occurred and progressed over the past 70 years to currently include a variety of blood/chemical biomarkers and new imaging modalities, and now long-term outcome datasets that can define risks with foresight not possible in the past. Undoubtedly, the emergence of digital artificial intelligence medical records and datasets will build upon this knowledge.

However, the resonance of comorbidities and risk factors in a physician’s consciousness, in part, also has been shaped by the medical era in which they trained. Currently, the allure of emerging genetic knowledge and new digital technologies may have unwittingly de-emphasized the importance of a complete history and physical examination. These basic tenets remain the foundation of good medical care. 

A recent example of this appeared in a European genetic study of 200,643 individuals seeking to establish the pathogenicity of cardiomyopathy (ARVC, HCM and DC) variants in the general population. This offered the possibility of identifying persons earlier in a population to perhaps practice precision medicine of prevention and surveillance for those individuals.

This could lead to a decrease of asymptomatic comorbidities and earlier appropriate therapy. After examination of extensive patient characteristics and demographic data, and electrocardiographic and cardiac MRI studies, the presence of family history data of heart disease and cardiac symptoms most commonly identified those individuals with adverse outcomes. The pathogenicity of the multiple gene variants and their overlap disclosed only a prevalence of 1.2% of arrhythmogenic right ventricular cardiomyopathy (ARVC), 2.6% of hypertrophic cardiomyopathy (HCM), and 3.1% of diabetic cardiomyopathy (DC) in this population.

Thus, after suspecting the possibility of asymptomatic comorbidities and risk in the population, the time-proven, age-old practice of a thorough history and physical examination accompanied by patient symptoms proved most helpful in identifying those with adverse outcomes.

Even in the modern era, performance of a complete history and physician examination guides the appropriate usage of biomarkers and diagnostic technologies in patient care. Research evidence of “risk factors” are being added and are constantly being updated (as demonstrated with the changing guidelines affecting hypercholesterolemia). Physicians must monitor the changing fields of risk factor knowledge.

Harold L. Kennedy MD, MPH, FACC, FESC, FAHA