CCC 2013: Aging Blood Vessels and the Role of Biomarkers

October 1, 2013

In two lively talks, Peter Liu, MD, Scientific Director of the University of Ottawa Heart Institute, took a big picture point of view. In his plenary presentation to the Vascular Summit, Dr. Liu highlighted the inextricable link between vascular health and aging. Vascular aging leads to vascular complications such as loss of elasticity in blood vessels and increased blood pressure. Research in mummies has shown that the presence of coronary artery disease was linked to age even thousands of years ago, so modern risk factors are not entirely to blame. Vascular disease is the result of a combination of aging and risk factors.

Our quality control over the production of proteins degrades over time due to oxidation and errors in protein folding. Removal mechanisms that clean out waste and abnormal molecules become overwhelmed and detritus builds up. This impacts organs throughout the body from the brain to the pancreas to the vascular system.

Aging challenges our inherent quality control mechanisms through immune responses that trigger systemic inflammation. This process, a good one for dealing with pathogens and controlling infection, made evolutionary sense when lifespans were shorter. But as we age, this same process becomes a key contributing factor in chronic disease. The presence of inflammatory cells changes and damages our blood vessels.

Can we impact this process? In model organisms such as fruit flies, flatworms and rats, reduced calorie diets have been shown to slow metabolism and reduce the production of free radicals. The result is slower aging and longer life spans, but we don’t yet know if these benefits translate to humans. We need to find ways to improve the removal of damaged proteins and modify abnormal protein production. We need to find ways to promote anti-inflammatory responses.

Echoing Dr. Andrew Pipe’s call for physical activity (see “Don’t Fear the Exercise Prescription”), Dr. Liu stressed that exercise is the primary thing any individual can do for themselves to impact all of these aging processes.

The Search for Biomarkers

In his second talk as part of a “State-of-the-Art” symposium, Dr. Liu offered a look at the history and future of biomarkers in cardiovascular care. In cardiovascular medicine, biomarkers are often used as indicators of disease or measures of risk. Examples include troponin for heart attack, low density lipoprotein (LDL) cholesterol and C-reactive protein for coronary artery disease, HbA1C for blood glucose and diabetes, and brain natriuretic peptide (BNP) for heart failure.

There are many other known biomarkers, but to be clinically useful, they must be sensitive enough to minimize false negative results, specific enough to minimize false positive results and consistent to generate reproducible results. They must also provide information that can guide clinical decision-making and be cost effective.

In 1976, Robert Roberts, MD, later President and CEO of the Heart Institute, was responsible for establishing creatine kinase as a practical biomarker for heart attack. It took another 10 years before it was widely adopted. Troponin was later found to be more specific and has supplanted creatine kinase.

Adolfo de Bold, PhD, a long-standing scientist at the Heart Institute, discovered atrial natriuretic peptide (ANP) and the heart’s endocrine function in the 1980s. This led to the discovery and use of BNP as a biomarker for heart failure. BNP was initially used to assess prognosis but is now used for diagnosis. BNP may also be able to help to guide therapy.

In 2007, a Heart Institute team led by Dr. Roberts identified 9p21, the single strongest genetic cardiovascular risk factor. Genetic biomarkers are not yet used clinically because they do not currently provide information that can guide care. However, the first ever bedside genetic test, RAPID GENE, developed by the Heart Institute, can be used to guide anticoagulation drug therapy.

In the future, say by the year 2020, Dr. Liu concluded, we can imagine that genetic screening will be common practice or that an adhesive patch for the skin might be available to warn of an impending heart attack. Dr. Liu’s own research targets the discovery of new biomarkers to address clinical needs in heart failure.