Chronological Age is Not a Good Component of Patient Risk Assessment
Chronological age is embedded in a great many standardized, widely-used protocols for patient risk assessment. Age-related diseases are, after all, age-related, and this use of chronological age has long seemed a reasonable choice. That said, we are now moving into an era in which novel means of measuring biological age are under development, such as epigenetic clocks.
Biological age is the burden of damage and dysfunction resulting from the causative processes of aging. Obviously, this should better reflect the odds of suffering age-related disease. While biological age correlates with chronological age, there is a great deal of room for differences between the two in any given individual. This development has also highlighted the point that a number of established functional measures, such as grip strength and other components of frailty assessment, particularly when these measures are combined together, might also be considered crude assessments of biological age.
This new knowledge regarding the measurement of age and processes of aging is making chronological age appear an ever worse choice for patient risk assessment. Different people age at meaningfully different rates. Today that occurs largely as the result of the combination of lifestyle choice, exposure to persistent pathogens, and the presence of environmental stressors such as particulate air pollution. In the decades ahead it will occur largely due to the use of interventions to repair and reverse causative processes of aging, progressively decoupling aging from the chronological passage of time.
Personalizing Cardiovascular Disease Risk Assessment: Is it Time to Forget About Chronologic Age?
It is commonly said that "age is just a number," and chronologic age, calculated as the time elapsed from birth, has been the primary way to define an individual's age. However, this method fails to account for the complex and diverse processes of aging. Indeed, a person's genetics along with their diet, lifestyle, and cumulative exposure to risk factors leads to significant heterogeneity in biologic age for persons of the same chronologic age. This creates a problem for cardiovascular risk calculators such as the Pooled Cohort Equation (PCE), because chronologic age is the most heavily weighted variable. Nearly all adults younger than 40 years have a low 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD), while most men older than 60 and women older than 65 years of age have at least an intermediate 10-year ASCVD risk from 7.5% to 20%, regardless of their traditional risk factor burden.
The shortcomings of chronologic age have led to an increased recognition that other measures are needed to better classify an individual's biologic age and ASCVD risk. Genetic biomarkers of DNA methylation and telomere length have been linked to acceleration of the aging processes, but the cost of testing and expertise needed for interpretation of the results limit their widespread use in clinical practice. Interestingly, even a subjective estimation of an individual's perceived age provides significant insight into their biologic age and survival. More direct quantification of arterial or vascular aging with the use of coronary artery calcium (CAC) scoring or noninvasive markers of arterial stiffness such as pulse-wave velocity (PWV) also better classify biologic age, which in turn improves ASCVD risk stratification relative to models that rely on chronologic age and may provide a more accurate and personalized estimate of ASCVD risk.
Compared with measuring systolic and diastolic blood pressure, measuring PWV provides distinct information on vascular health that is specifically related to vascular compliance and distensibility and is an early marker of poor vascular health, even before the development of hypertension. PWV is also strongly associated with cardiovascular outcomes and improves risk prediction beyond traditional cardiovascular risk factors, with a 30% increased risk for cardiovascular disease (CVD) for every 1 standard deviation higher PWV. As such, PWV is one simple method to improve the measurement of biologic age.