Not all lipid measurements require fastingDriver SL et al., J Am Coll Cardiol. 2016
Fasting or Nonfasting Lipid Measurements - It Depends on the Question
Driver SL, Martin SS., GLuckman TJ, et al.,
J Am Coll Cardiol. 2016;67(10):1227-1234. doi:10.1016/j.jacc.2015.12.047
The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults emphasises a patient’s global risk of developing atherosclerosis CV disease (ASCVD), by focussing on risk-benefit profiles of specific classes of drugs.
In order to determine the appropriate treatment of individuals at risk of ASCVD, lipid and lipoprotein measurements are done. This paper re-examines the need for fasting for these measurements, which depends on the specific question being posed, depending on the clinical scenario.
Historical basis for fasting lipidsInitial classifications in hyperlipidaemia as proposed in 1967, were genetic and required fasting. The introduction of the Friedewald formula then allowed calculation of an LDL-c level using fasting data. The National Cholesterol Education Program (NCEP) guidelines reinforced the use of fasting lipids, by focussing on specific LDL goals.
The 2013 guidelines matched intensity of LDL-lowering therapy to baseline ASCVD risk, and specific patient categories were defined, for which statins had been shown to be first-line therapy. For those patients not fulfilling criteria for one of the four categories, additional factors to consider were formulated that can help guide treatment decisions.
Recent insights have challenged the value of LDL-c levels as decision points. While the general utility of a fasting lipid panel is still emphasised in the guideline, for practical purposes, the traditional reliance on fasting lipids may no longer apply to answer most questions. Six clinical scenarios are discussed.
Question 1: What is the initial risk for my untreated, primary prevention patient?While higher LDL-c levels are associated with higher rates of CV and all-cause mortality, the new guidelines do not use LDL-c to predict risk. The Friedewald formula is nog accurate at low LDL-c (<70 mg/dL) and high triglycerides (TGs >400 mg/dL) and the accuracy of directly measured LDL-c across the spectrum of possible values has not been demonstrated. And while the Friedewald formula estimates cholesterol contained in LDL, IDL and Lp(a), certain commercial direct LDL assays seem to only measure cholesterol associated with LDL and IDL.
Lowering non-HDL-c cut-points only minimally can result in substantial reclassification of patients to higher risk categories. Also, biological variability and seasonal LDL variation suggest that arbitrary fixed targets can be debated.
Instead, the purpose of LDL-c lowering as primary prevention is to lower the risk of a first event. Several CV risk estimators have been developed, which include total cholesterol and HDL-c as only lipid components. These measures vary little between fasting and non-fasting states.
Thus, for risk assessment alone, fasting or non-fasting measurement can be used.
Question 2: How should I screen and follow patients with a family history of genetic hyperlipidaemia or premature ASCVD?Fasting LDL-c>190 mg/dL is the most common lipid abnormality that points in the direction of familial hyperlipidemia. A fasting lipid profile is preferred for first-degree relatives of those with premature ASCVD. Although a non-fasting non-HDL >220 mg/dL can indicate genetic hyperlipidemia that requires further evaluation, significantly elevated TGs may also point at genetic lipid disorders.
Thus, fasting lipids, especially if combined with apolipoprotein B levels, can be helpful to distinguish between different dyslipidaemic conditions, as well as define the risk of pancreatitis.
Question 3: What if I want to clarify the diagnosis of metabolic syndrome?Metabolic syndrome is defined by the presence of at least three of several risk factors, including low HDL-c and high TGs. Sharing a diagnosis of metabolic syndrome has been described to increase the individual’s risk perception and motivation to improve health behaviour. Identifying metabolic risk factors can guide intensive lifestyle interventions.
The added benefit of a fasting profile should be balanced against possible practical consequences such as added expenses and time costs. Elevated TGs, HbA1c>5.6 and a low HDL-c level can already give an impression of metabolic risk factors and take away the need for a return fasting visit. This may speed up a diagnosis and expedite implementation of lifestyle modification.
Question 4: What is the residual risk for my treated patient?Calculated total cholesterol and non-HDL cholesterol risk estimates are based on those naïve to lipid-lowering therapies. Thus, on-treatment lipid levels cannot simply be put into an ASCVD risk estimator. Instead, it should be considered that a relative risk reduction of about 20% is achieved per 1 mmol/L (39 mg/dl) of LDL-c lowering with moderate or high-intensity statin therapy.
Response to treatment can better be assessed with a fasting lipid panel and this measurement at follow-up can provide prognostic value. Several guidelines now no longer recommend fixed lipid targets, but advise non-fasting non-HDL-c to gauge adequacy of response to treatment. This is particularly important in secondary prevention, as adequate response to therapy has been linked to attenuation of progression of atherosclerosis. When assessing response to treatment, it is important to gauge and stimulate adherence.
Question 5: How should I assess patients with or at risk for pancreatitis?Fasting lipids should be measured in those with pancreatitis, to determine whether hypertriglyceridaemia is the cause. A repeat fasting measurement can help assess the risk of recurrent pancreatitis. Certain subpopulations may benefit from screening fasting TGs, to identify those at risk of pancreatitis.
Question 6: Can hypertriglyceridaemia be diagnosed with nonfasting triglycerides?A recent AHA statement suggests that a non-fasting TG level of >200 mg/dL can identify hypertriglyceridemic status. When fasting TGs is <150, a low-fat breakfast should not increase postprandial TG levels by more than 20%. Follow-up fasting levels in those with non-fasting TG of 175 mg/dL is not needed, but lifestyle modifications should still be discussed. If non-fasting TG exceeds 200 mg/dL, a follow-up fasting panel is advised.
Thus, in certain clinical scenarios (Questions 2, 4, 5 and 6), a fasting lipid panel offers useful clinical information, while in other situations non-fasting levels suffice. The need for a more inconvenient fasting measurement depends on the question that needs to be answered.
Find this article online at JACC