What is CardioMetabolic Risk?
Cardio-metabolic risk has been defi ned as "the cluster of modifi able risk factors and markers that identify individuals at increased risk for cardiovascular disease (myocardial infarction, stroke, peripheral arterial disease) and type 2 diabetes1."
The National Cholesterol Education Program (NCEP)'s Adult Treatment Panel III (ATP III) has identifi ed the metabolic syndrome/insulin resistance syndrome as a major risk factor for CVD2. The National Heart, Lung and Blood Institute and the American Heart Association in a 2003 conference3 agreed that CVD is the primary clinical outcome of metabolic syndrome; when the Framingham Heart Study investigators analyzed their data according to the NCEP-ATP III criteria for the conference, the metabolic syndrome predicted about 25% of all new-onset CVD and the presence of metabolic syndrome was highly predictive of new-onset DM2.
NCEP-ATP III criteria for identifying metabolic syndrome include:
– hypertension/elevated blood pressure
– abdominal obesity
– atherogenic dyslipidemia (low HDL cholesterol, elevated triglycerides, elevated LDL cholesterol)
– prothrombotic/pro-infl ammatory state
– insulin resistance/glucose intolerance
Which Biomarkers are Included in the Profi le
High Sensitivity C-Reactive Protein (hs-CRP)
C-reactive protein (CRP) is an established marker of infl ammation and has recently been suggested to be an important contributor to pro-infl ammatory and pro-thrombotic elements of CVD risk. Extremely high CRP levels are seen in acute infl ammatory states, but the small elevations that are indicative of the pro-infl ammatory and pro-thrombotic states implicated in the metabolic syndrome require high sensitivity assays, and are thus referred to as hs-CRP levels. These high sensitivity assays have recently been developed for use with blood spots.
– Overweight, obese, insulin resistant and diabetic individuals typically have elevated CRP levels7
– Studies have shown correlations between elevated CRP and increased risk of future heart attacks, ischemic stroke, and peripheral arterial disease
– Elevated CRP levels have been found to predict the development of DM2
– Increased CRP levels, which correlate inversely with insulin sensitivity, have been found in individuals with polycystic ovarian syndrome and may be a marker of early cardiovascular risk in these patients13,14
– Lifestyle changes such as aerobic exercise, weight loss and smoking cessation have been known to lower CRP
– Medications like aspirin and statins can lower CRP levels
– Levels below 3.0 mg/L are considered to be normal; 3.1 to 10 mg/L is elevated, in the context of CVD risk, and above 10 mg/L is very high, more likely indicating an acute infl ammatory event due to infection or trauma
Dried blood spot technology has effectively been used for measurement of insulin levels. The requirement to measure fasting insulin makes convenient blood spot collection at home especially advantageous to patients.
– High fasting insulin levels are a good indicator of insulin resistance, which occurs when the cellular response to the presence of insulin is impaired resulting in a reduced ability of tissues to take up glucose for energy production. Chronically high insulin levels are seen as the body attempts to normalize blood sugar levels
– High fasting insulin indicates the presence of insulin resistance whether or not the patient shows glucose intolerance
– The normal range for fasting insulin is 1 – 15 μIU/mL, but levels between 2 and 6 μIU/mL are optimal
Hemoglobin A1c (HbA1c)
HbA1c is a measure of red blood cell hemoglobin glycation, indicating mean glycemia over the previous 3 months, which is the lifespan of circulating red blood cells. It can therefore indicate impaired glucose tolerance even when occasional fasting plasma glucose measurements are normal.
– The American Diabetes Association's recommendation is to measure HbA1c every 3-6 months; normal levels are 4 – 6%
– Levels of HbA1c above 6% in diabetics are associated with an increased risk of developing complications such as eye disease, kidney
disease, nerve damage, heart disease, and stroke, therefore treatment should aim to keep levels below 7%
– An HbA1c of more than 6% can predict CVD and DM2 in high-risk individuals
Hypertriglyeridemia, a triglyceride level >150 mg/dL, is an established indicator of atherogenic dyslipidemia and is often found in untreated DM2 and obesity.
– Studies have shown that levels above 200 mg/dL indicate an increased risk of heart disease and stroke2
– Some studies have shown that fasting triglyceride levels lower than 100 mg/dL should be considered as a more optimal cutoff in coronary heart disease risk assessment
– The NCEP-ATP III defi nes levels of 150 mg/dL or above as one of the diagnostic criteria for metabolic syndrome
Advantages of a Simple Blood Spot Test to Assess CardioMetabolic Risk
– A simple, almost painless fi nger prick provides the few drops of blood required, which are collected on the fi lter paper provided
– Convenient sample collection at home – no phlebotomist required
– Easy shipment of samples by regular mail for analysis – samples are stable for several weeks at room temperature
– Dried blood spots carry no infection risk – infectious agents are inactivated when dry
– Excellent correlation with serum/plasma and whole blood assays