scholarly journals Hepatic Lipase, Genetically Elevated High-Density Lipoprotein, and Risk of Ischemic Cardiovascular Disease

2009 ◽  
Vol 94 (4) ◽  
pp. 1264-1273 ◽  
Author(s):  
Trine Holm Johannsen ◽  
Pia R. Kamstrup ◽  
Rolf V. Andersen ◽  
Gorm B. Jensen ◽  
Henrik Sillesen ◽  
...  

Abstract Context: Hepatic lipase influences metabolism of high-density lipoprotein (HDL), a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease and ischemic cerebrovascular disease). Objective: We tested the hypothesis that genetic variation in the hepatic lipase genetic variants V73M, N193S, S267F, L334F, T383M, and −480c>t influence levels of lipids, lipoproteins, and apolipoproteins and risk of ICD. Design: For the cross-sectional study, we genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971 individuals included in the prospective study, 1747 of whom had incident ICD during 28 yr of follow-up. For the case-control studies, 2110 ischemic heart disease patients vs. 4899 controls and 769 ischemic cerebrovascular disease patients vs. 2836 controls, respectively, were genotyped. Follow-up was 100% complete. Results: HDL cholesterol was higher by 0.21 mmol/liter in S267F heterozygotes, by 0.06 mmol/liter in −480c>t heterozygotes, and by 0.13 mmol/liter in −480c>t homozygotes, as compared with noncarriers. These HDL increases theoretically predicted hazard ratios for ICD of 0.87 [95% confidence interval (CI) 0.84–0.90], 0.96 (95% CI 0.95–0.97), and 0.91 (95% CI 0.89–0.94), respectively; this calculation assumes that genetically elevated HDL levels confer decreased risk similar to common HDL elevations. In contrast, when all cases and controls were combined, the observed odds ratios for ICD for these three genetic variants vs. noncarriers were 1.19 (0.76–1.88), 1.04 (0.96–1.13), and 1.08 (0.89–1.30), respectively. Hazard/odds ratios for ICD in carriers vs. noncarriers of the four remaining hepatic lipase genetic variants did not differ consistently from 1.0. Conclusion: Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ICD.

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Catherine Rahilly-Tierney ◽  
Howard D Sesso ◽  
J. Michael Gaziano ◽  
Luc Djousse

BACKGROUND: Few studies have examined prospectively the relationship between baseline high-density lipoprotein (HDL) cholesterol and longevity. OBJECTIVES: We sought to examine whether higher HDL levels were associated with lower risk of all-cause, cardiovascular (CVD), and non-CVD mortality prior to age 90 in the Physicians’ Health Study (PHS). METHODS: We considered a baseline cohort of 1351 PHS participants who provided bloods between 1997 and 2001 and were old enough to reach age 90 by March 4, 2009. Included subjects had complete baseline data on HDL and total cholesterol; lifestyle factors including smoking, exercise, alcohol consumption, and BMI; and comorbidities including hypertension, diabetes mellitus, congestive heart failure, cancer, and stroke. We used Cox proportional hazards to determine the HRs and 95% CIs for all-cause, CVD, and non-CVD mortality prior to age 90, adjusting for baseline age, co-morbidities, and non-HDL cholesterol. RESULTS: At baseline, the cohort had a mean (SD) age of 81.9 (2.9) years and a mean (SD) HDL cholesterol of 44.8(16.5) mg/dL. After a mean follow-up of 6.8 years (maximum 12.3 years), 501 (37.1%) of men died prior to age 90. In multi-variable adjusted analyses, men in the highest HDL-C quartile (≥54.1 mg/dL) had a 28% lower risk (HR 0.72, 95% CI 0.55-0.95) of all-cause mortality prior to age 90 compared to men in the lowest HDL-C quartile (<32.8 mg/dL). From the lowest to highest HDL quartile, age-adjusted HR(95%CI) for CVD mortality prior to age 90 were 0.66 (0.44-0.99), 0.58 (0.38-0.90), and 0.53 (0.34-0.82) (p for trend 0.004). There was no significant association between baseline HDL cholesterol and non-CVD death. CONCLUSION: In a cohort of older male physicians with long-term follow-up, baseline HDL cholesterol was inversely associated with the risk of dying prior to age 90, largely explained by an inverse association between HDL and CVD mortality.


Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 362 ◽  
Author(s):  
Fumiaki Ito ◽  
Tomoyuki Ito

Lipid markers are well-established predictors of vascular disease. The most frequently measured lipid markers are total cholesterol, high-density lipoprotein (HDL)-cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglyceride. HDL reduces atherosclerosis by multiple mechanisms, leading to a reduced risk of cardiovascular disease, and HDL-C, as a metric of HDL quantity, is inversely associated with cardiovascular disease, independent of LDL-C. However, the quality of the HDL appears to be more important than its quantity, because HDL loses its antiatherogenic functions due to changes in its composition and becomes “dysfunctional HDL”. Although there is evidence of the existence of “dysfunctional HDL”, biomarkers for monitoring dysfunctional HDL in clinical practice have not yet been established. In this review, we propose a new lipid panel for the assessment of dysfunctional HDL and lipoprotein-related atherosclerotic cardiovascular disease. The lipid panel includes the measurement of lipid peroxide and triglyceride contents within HDL particles.


1989 ◽  
Vol 82 (2) ◽  
pp. 91-92 ◽  
Author(s):  
C H Bolton ◽  
E Mulloy ◽  
J Harvey ◽  
L G Downs ◽  
M Hartog

Plasma and lipoprotein cholesterol and triglycerides, and plasma apolipoproteins AI, AII and B were compared in patients with chronic airflow limitation, and normal controls matched for body mass index. The controls were non-smokers, and free from respiratory disease. High-density lipoprotein (HDL) cholesterol concentration was significantly elevated in the patients, due mainly to a raised HDL2 cholesterol level. HDL triglyceride was significantly lower in the patients. All other lipids were not different from normal. Apolipoprotein AI levels were significantly raised in the patients but other apolipoproteins were unchanged. The changes found may account in part for the fact that patients with chronic airflow limitation have a lower incidence of atherosclerotic heart disease.


Author(s):  
Christian M. Madsen ◽  
Anette Varbo ◽  
Børge G. Nordestgaard

The vast majority of research about HDL (high-density lipoprotein) has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within cardiovascular disease prevention; however, failures with therapies aimed at increasing HDL cholesterol has left questions as to what the role and function of HDL in human health and disease is. Recent observational studies have further shown that extreme high HDL cholesterol is associated with high mortality leading to speculations that HDL could in some instances be harmful. In addition, evidence from observational, and to a lesser extent genetic, studies has emerged indicating that HDL might be associated with the development of other major noncardiovascular diseases, such as infectious disease, autoimmune disease, cancer, type 2 diabetes, kidney disease, and lung disease. In this review, we discuss (1) the association between extreme high HDL cholesterol and mortality and (2) the emerging human evidence linking HDL to several major diseases outside the realm of cardiovascular disease.


1981 ◽  
Vol 61 (2) ◽  
pp. 235-240 ◽  
Author(s):  
T. R. Gamlen ◽  
E. Layward ◽  
F. McTaggart ◽  
D. P. R. Muller

1. Significant positive correlations were found between the lipoprotein lipase and hepatic lipase activities of post-heparin plasma samples and plasma high-density-lipoprotein (HDL) cholesterol concentrations in 21 children with hyperlipidaemia and six normal adult males. 2. A significant positive correlation was also observed between the two lipase activities and the ratio of HDL cholesterol to apoprotein AI (apo AI) concentrations. 3. These findings provide further evidence that a significant proportion of HDL and possibly the HDL2 subfraction is formed during the clearance of triglyceride-rich lipoproteins.


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