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Before 2009 essentially all societies, guidelines, and statements required fasting before measuring a lipid profile for cardiovascular risk prediction. This was mainly due to the increase seen in triglycerides during a fat tolerance test. However, individuals eat much less fat during a normal day and nonfasting triglycerides have been shown to be superior to fasting in predicting cardiovascular risk. Lipids and lipoproteins only change minimally in response to normal food intake: in four large prospective studies, maximal mean changes were +0.3 mmol/L (26 mg/dL) for triglycerides, -0.2 mmol/L (8 mg/dL) for total cholesterol, -0.2 mmol/L (8 mg/dL) for LDL cholesterol, and -0.1 mmol/L (4 mg/dL) for HDL cholesterol. Further, in 108,602 individuals from the Copenhagen General Population Study in random nonfasting samples, the highest versus the lowest quartile of triglycerides, total cholesterol, LDL cholesterol, remnant cholesterol, non-HDL cholesterol, lipoprotein(a), and apolipoprotein B were all associated with higher risk of both ischaemic heart disease and myocardial infarction. Finally, lipid-lowering trials using nonfasting blood samples for assessment of lipid levels found that reducing levels of nonfasting lipids reduced the risk of cardiovascular disease. To date there is no sound scientific evidence as to why fasting should be superior to nonfasting when evaluating a lipid profile for cardiovascular risk prediction. Indeed, nonfasting samples rather than fasting samples have many obvious advantages. First, it would simplify blood sampling in the laboratory. Second, it would benefit the patient, avoiding the inconvenience of fasting and therefore needing to have blood drawn early in the day. Third, for individuals with diabetes, the risk of hypoglycaemia due to fasting would be minimised. Many countries are currently changing their guidelines towards a consensus on measuring a lipid profile for cardiovascular risk prediction in the nonfasting state, simplifying blood sampling for patients, laboratories, and clinicians worldwide., (Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Background: Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events., Methods and Results: We cross-sectionally studied 33 391 individuals 20 to 95 years of age from the Copenhagen General Population Study. We also studied 9319 individuals 20 to 93 years of age from the Copenhagen City Heart Study, 1166 of whom developed cardiovascular events during 14 years of follow-up. Compared with fasting levels, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, and albumin levels were reduced up to 3 to 5 hours after the last meal; triglycerides levels were increased up to 6 hours after the last meal; and non-HDL cholesterol level, apolipoprotein A1 level, apolipoprotein B level, ratio of total cholesterol to HDL cholesterol, and ratio of apolipoprotein B to apolipoprotein A1 did not change in response to normal food intake. The maximum changes after normal food and fluid intake from fasting levels were -0.2 mmol/L for total cholesterol, -0.2 mmol/L for low-density lipoprotein cholesterol, -0.1 mmol/L for HDL cholesterol, and 0.3 mmol/L for triglycerides. Highest versus lowest tertile of nonfasting total cholesterol, non-HDL cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, triglycerides, ratio of total cholesterol to HDL cholesterol, and ratio of apolipoprotein B/apolipoprotein A1 and lowest versus highest tertile of nonfasting HDL cholesterol and apolipoprotein A1 predicted 1.7- to 2.4-fold increased risk of cardiovascular events., Conclusions: Lipid profiles at most change minimally in response to normal food intake in individuals in the general population. Furthermore, nonfasting lipid profiles predicted increased risk of cardiovascular events.

Background: Familial hypercholesterolemia (FH) is a condition with very high concentrations of low-density lipoprotein (LDL) cholesterol and high risk of ischemic heart disease including myocardial infarction. However, there is limited and contradictory information on whether FH and high LDL cholesterol per se confer high risk of ischemic stroke. We tested the hypotheses that individuals in the general population with FH and/or high LDL cholesterol have higher risk of ischemic stroke.Methods: The associations of FH and high LDL cholesterol with ischemic stroke risk were tested in both causal, genetic, and observational analyses using 106 412 individuals from the CGPS (Copenhagen General Population Study; 2823 ischemic strokes and 3792 myocardial infarctions) and/or 10 372 individuals from the CCHS (Copenhagen City Heart Study; 945 ischemic strokes and 1142 myocardial infarctions). FH causative mutations were LDLR W23X(rs267607213), W66G(rs121908025) and W556S, and APOB R3500Q(rs5742904). A Mendelian randomization design tested whether high LDL cholesterol per se has a causal effect on ischemic stroke risk, using a combination of the FH causative mutations and common genetic variants associated with high LDL cholesterol.Results: The cumulative incidences in individuals in the CGPS with and without FH causative mutations were similar for ischemic stroke ( P=0.50) but not for myocardial infarction ( P<0.001): at age 80 years, 4% and 7% of these individuals developed ischemic stroke and 20% and 8% myocardial infarction, with similar results in the CCHS. There was no association between clinical FH and ischemic stroke, except if personal premature ischemic heart disease was included in the clinical FH criteria. Ischemic heart disease at baseline was associated with higher ischemic stroke risk, explaining the higher ischemic stroke risk in those with high LDL cholesterol. For a 1 mmol/L higher LDL cholesterol, the genetic causal risk ratio was 1.11 (0.62-2.02) for ischemic stroke and 1.45 (1.08-1.93) for myocardial infarction.Conclusions: FH and high LDL cholesterol did not confer an increased risk of ischemic stroke. A positive association with ischemic stroke observed for some clinical FH criteria and high LDL cholesterol appears to be due to previous ischemic heart disease, rather than to high LDL cholesterol per se. [ABSTRACT FROM AUTHOR]

Background--Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown. Methods and Results--We studied 60 608 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the Copenhagen Ischemic Heart Disease study, of whom 10 668 had IHD diagnosed between 1977 and 2011. We genotyped for variants affecting levels of nonfasting remnant cholesterol, LDL cholesterol, C-reactive protein by CRP alleles, and C-reactive protein by IL6R alleles. Using a multidirectional mendelian randomization design, we investigated possible causal associations between the lipoproteins and C-reactive protein and between the lipoproteins and IHD. A 1-mmol/L(39 mg/dL) higher level of nonfasting remnant cholesterol was associated observationally with a 37% (95% confidence interval, 35-39) higher C-reactive protein level and causally with a 28% (95% confidence interval, 10-48) higher level. For LDL cholesterol, a 1-mmol/L (39-mg/dL) higher level was associated observationally with a 7% (95% confidence interval, 6-7) higher C-reactive protein level, but we found no causal association. Likewise, higher levels of C-reactive protein did not associate causally with elevated nonfasting remnant cholesterol or LDL cholesterol. Finally, the causal risk ratio for IHD for a 1-mmol/L (39-mg/dL) higher level was 3.3 (95% confidence interval, 2.1-5.2) for nonfasting remnant cholesterol and 1.8 (95% confidence interval, 1.5-2.2) for LDL cholesterol. The causal associations for remnant cholesterol were present even in those without diabetes mellitus and obesity. Conclusions--Elevated nonfasting remnant cholesterol is causally associated with low-grade inflammation and with IHD, whereas elevated LDL cholesterol is associated causally with IHD without inflammation. [ABSTRACT FROM AUTHOR]