Heart disease is one of the leading causes of death worldwide. It accounts for about 1 of every 3 deaths in the United States. Epidemiological and interventional studies have demonstrated the existence of an inverse relationship between concentration of high density lipoprotein cholesterol (HDL-C, the “good” cholesterol) and coronary heart diseases. Unfortunately, therapies to increase the concentration of “good” cholesterol have had limited success, and standard approaches to measure function of HDL-C are too unwieldy to apply to patients. However, researchers have recently developed a novel test that can quickly assess heart disease risk based on HDL-C function, which could readily be applied in clinical settings.
Challenges Predicting Heart Disease Risk From HDL-C
There were several tests conducted that increased HDL-C concentration, with the goal of reducing the risk for cardiovascular diseases. However, the clinical efficacy of increasing plasma HDL-C concentration has not yet been proven. In fact, recently published outcome trials observed that therapies with significant increase in HDL-C concentration failed to report clinical benefits. Furthermore, genetic variants related to high HDL-C concentration are not consistently associated with improved cardiovascular outcomes. These findings highlight the limitations of using HDL-C concentration for assessing cardiovascular risk and the limitations of therapies that target HDL-C.
HDL has a variety of functions that may contribute to its cardiovascular-protective effects, including reverse cholesterol transport and anti-inflammatory, and antioxidative properties. Although the relative contribution of each function of HDL towards its cardiovascular protective effects is not clear, one of its chief functions is thought to be mediating the removal of cholesterol from blood vessel walls (known as cholesterol efflux capacity). Recent animal and clinical studies have indicated that cholesterol efflux capacity of HDL is a better gauge of cardiovascular disease development than HDL-C levels on their own. In other words, a patient with low levels of HDL-C but optimal cholesterol efflux capacity could be protected against heart disease to a greater degree than a patient with high levels of HDL-C but low cholesterol efflux capacity. However, cholesterol efflux capacity measured by standard research protocols is very complex and time-consuming, which limits usefulness for patient testing.
Cholesterol Uptake Capacity Can Quickly Assess Patient Risk
Recently, a team of Japanese researchers led by Amane Harada of Sysmex Corporation and Ryuji Toh of Kobe University Graduate School of Medicine developed the first of it’s kind test for HDL-C function that is simple enough for clinical use. This test determines the ability of HDL-C to accept additional cholesterol (termed cholesterol uptake capacity) with a turnaround time of less than 6 hours. Importantly, researchers found a good correlation between the cholesterol uptake capacity test and well-established cholesterol efflux capacity.
The researchers evaluated the test in 156 patients who had undergone revascularization (such as a stent or bypass) due to coronary artery disease and who had subsequently decreased their low-density lipoprotein (“bad”) cholesterol to <100 mg/dL. The study found that low cholesterol uptake capacity in these patients after treatment was significantly associated with the recurrence of coronary lesions. The researchers also determined that combining cholesterol uptake capacity with established cardiovascular disease risk factors significantly improved the power to forecast which patients would re-develop heart disease.
Although further trials are warranted to validate this test, the opportunities for an easy way to measure cardiovascular disease risk are very promising.
Image courtesy of pixabay.com
