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Background and Aims: We estimated the extent of undertreatment and overtreatment with cholesterol-lowering therapy according to European guidelines in individuals in the Danish general population without ischemic cardiovascular disease and diabetes., Methods: We examined 92,348 such individuals aged 35-100 years recruited from 2004 through 2014 in the Copenhagen General Population Study. Each individual was assigned their 10-year risk of fatal cardiovascular disease according to the European SCORE chart based on age, sex, smoking, total cholesterol, and systolic blood pressure. European guidelines recommend cholesterol-lowering therapy definitely at ≥10% risk and LDL cholesterol ≥1.8 mmol/L, definitely at 5-9% risk and LDL cholesterol ≥2.5 mmol/L, possibly at 1-4% risk and LDL cholesterol ≥3 mmol/L, but not at <1% risk., Results: 3858 individuals had ≥10% risk, 16,255 had 5-9% risk, 49,131 had 1-4% risk, and 23,104 had <1% 10-year risk of fatal cardiovascular disease. In these groups, 81%, 86%, 93%, and 99% did not receive cholesterol-lowering therapy. Definite undertreatment and overtreatment according to guidelines were found in 19% and 0.2% or in 187,660 and 1570 per million 35-100 year olds without ischemic cardiovascular disease and diabetes. If definite and possible undertreatment and overtreatment were combined, the corresponding numbers were 52% and 3% or 519,416 and 29,194 per million., Conclusions: In the Danish general population, ∼190,000 per million 35-100 year olds without ischemic cardiovascular disease and diabetes are not treated to LDL cholesterol goals according to European guidelines. Conversely, ∼1600 per million received cholesterol-lowering therapy without endorsement in European guidelines., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Increased nonfasting remnant cholesterol, like increased LDL cholesterol, is causally associated with increased risk for ischemic heart disease (IHD). We tested the hypothesis that extreme concentrations of nonfasting remnant and LDL cholesterol are equal contributors to the risk of IHD, myocardial infarction (MI), and all-cause mortality., Methods: We compared stepwise increasing concentrations of nonfasting remnant and LDL cholesterol for association with risk of IHD, MI, and all-cause mortality in approximately 90 000 individuals from the Danish general population. During up to 22 years of complete follow-up, 4435 participants developed IHD, 1722 developed MI, and 8121 died., Results: Compared with participants with nonfasting remnant cholesterol <0.5 mmol/L (19.3 mg/dL), hazard ratios for IHD ranged from 1.3 (95% CI 1.1-1.5) for remnant cholesterol of 0.5-0.99 mmol/L (19.3-38.2 mg/dL) to 2.4 (1.9-2.9) for remnant cholesterol of ≥1.5 mmol/L (58 mg/dL) (P for trend <0.001). Compared with participants with LDL cholesterol <3.0 mmol/L (115.8 mg/dL), hazard ratios for IHD ranged from 1.3 (1.1-1.5) for LDL cholesterol of 3-3.99 mmol/L (115.8-154 mg/dL) to 2.3 (1.9-2.8) for LDL cholesterol of ≥5 mmol/L (193 mg/dL) (P < 0.001). Corresponding hazard ratios for MI ranged from 1.8 (1.4-2.3) to 3.4 (2.5-4.8) for remnant cholesterol (P < 0.001), and from 1.7 (1.4-2.2) to 4.7 (3.5-6.3) for LDL cholesterol (P < 0.001). Nonfasting remnant cholesterol concentrations were associated stepwise with all-cause mortality ranging from hazard ratio 1.0 (0.9-1.1) to 1.6 (1.4-1.9) (P < 0.001), whereas LDL cholesterol concentrations were associated with decreased all-cause mortality risk in a U-shaped pattern, with hazard ratios from 0.8 (0.7-0.8) to 0.9 (0.8-1.0) (P = 0.002). After mutual adjustment, LDL cholesterol best predicted MI, and remnant cholesterol best predicted all-cause mortality., Conclusions: Both lipoproteins were associated equally with risk of IHD and MI; however, only nonfasting remnant cholesterol concentrations were associated stepwise with increased all-cause mortality risk., (© 2015 American Association for Clinical Chemistry.)

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.

Abstract: Ischemic cardiovascular disease and obstructive pulmonary disease involve inflammation. Leukotrienes may be important pro-inflammatory mediators. We tested the hypothesis that the (-1072)G>A and (-444)A>C promoter polymorphisms of leukotriene C4 synthase confer risk of transient ischemic attack (TIA), ischemic stroke, ischemic heart disease (IHD), asthma, and chronic obstructive pulmonary disease (COPD). We genotyped individuals from the Danish general population, the Copenhagen City Heart Study, and Danish patients with IHD/coronary atherosclerosis, the Copenhagen Ischemic Heart Disease Study. We used prospective (n =10,386), cross-sectional (n =10,386), and case-control (n =2392+5012) designs. Allele frequency was 0.07 for (-1072)A and 0.29 for (-444)C. Cumulative incidence for TIA was higher for (-1072)AA versus GG genotype (log-rank: p <0.001), and lower for (-444)CC versus AA genotype (log-rank: p =0.03). Cumulative incidence for ischemic stroke was also lower for (-444)CC versus AA genotype (log-rank: p =0.04). Multifactorially adjusted hazard ratios for TIA were 5.2(95% CI:1.9–14) for (-1072)AA versus GG genotype, and 0.4(0.2–1.0) for (-444)CC versus AA genotype. Corresponding values were 1.9 (0.7–5.2) and 0.7 (0.5–1.0) for ischemic stroke, and 0.8 (0.4–1.6) and 1.0 (0.9–1.2) for IHD. In the case-control study, corresponding multifactorially adjusted odds ratios for IHD/coronary atherosclerosis were 0.5 (0.2–1.3) and 1.2 (1.0–1.5). These genotypes were not associated with risk of asthma or COPD. Leukotriene C4 synthase promoter genotypes influence risk of TIA and ischemic stroke, but not risk of IHD/coronary atherosclerosis, asthma, or COPD. [Copyright &y& Elsevier]