Traditional risk factors account for about 50% of cardiovascular disease (CVD) risk, and numerous individuals develop CVD with cholesterol and blood pressure deemed satisfactory. Many high-risk subjects exhibit both conventional CVD risk factors alongside non-conventional emerging factors/markers such as C-reactive protein (CRP).
There is at present a plethora of emerging risk factors, many of which modifiable, making future hierarchical classification essential while waiting for a global calculator to assess residual risk in patients receiving current standards of care. Certain overlapping candidate risk factors will undoubtedly need to be ranked according to their discrimination potency in prospective interventions on CVD.
There is mounting evidence that atherogenic dyslipidemia (low HDL-C and/or high triglycerides (TG)), systemic inflammation and other components of the metabolic syndrome (MetS) may represent sizeable and potentially modifiable components of residual risk in patients on current standards of care. Establishing the presence of MetS in a given individual may identify subjects at risk for diabetes and/or premature CVD, and help categorize residual risk remaining on standard therapies.
Regarding systemic inflammation, recent results from JUPITER showed how effective an intervention targeting raised CRP can translate into improved outcomes. Low HDL-C and/or high TG often coexist with raised apolipoprotein B (apoB), elevated non-HDL-C and reduced LDL particle size. In the INTERHEART study, an epidemiological survey of risk factors for first myocardial infarction, the apoB/apoAI ratio was the strongest predictor for incident MI. Such a ratio, suited to enhance epidemiological potency, divides an atherogenic numerator (apoB, surrogate for non-HDL-C) with an atheroprotective denominator (apoA-I, surrogate for HDL-C).
Besides their usefulness for establishing the presence of MetS, low HDL-C and/or high TG are useful markers for risk stratification of patients with various metabolic conditions, including those with LDL-C in the low-to-normal range. Reducing the modifiable components of residual risk associated with HDL-C and/or high TG may allow for additional reduction in relative/absolute CVD risk. The ADA/ACC 2008 recommendations identify apoB and non-HDL-C as residual risk components to be addressed as secondary treatment goals in patients with cardiometabolic risk and dyslipoproteinemia.