Cholesterol-Overloaded HDL Particles Are Independently Associated With Progression of Carotid Atherosclerosis in a Cardiovascular Disease-Free Population

Qi, Yue; Fan, Jia; Liu, Jing; Wang, Wei; Wang, Miao; Sun, Jiayi; Liu, Jun; Xie, Wuxiang; Fan, Zhanming; Li, Yan; Zhao, Dong

doi:10.1016/j.jacc.2014.11.019

Cited by 82 publications

(72 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This original observation will prompt new survey studies in larger all-gender prospective cohorts in order to evaluate the value added by IF1 over existing predictors and to assess its usefulness in routine clinical practice. As compared to other emerging HDL-related biomarkers that have been also proven to be better than HDL-C level, such as HDL-P and subclasses measured by NMR [40, 41] or cholesterol efflux capacity measured by cellular assays [42], measurement of IF1 by immunoassay is technically more feasible in terms of analytical requirements, accessibility, turnaround time, and traceability. In the future, IF1 measurement could be clinically useful for better prognosis in populations at high risk or in the setting of pharmacotherapy.…”

Section: Discussionmentioning

confidence: 99%

Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study

Genoux

Lichtenstein

Ferrières

et al. 2016

BMC Med

View full text Add to dashboard Cite

BackgroundEpidemiological and observational studies have established that high-density lipoprotein cholesterol (HDL-C) is an independent negative cardiovascular risk factor. However, simple measurement of HDL-C levels is no longer sufficient for cardiovascular risk assessment. Therefore, there is a critical need for novel non-invasive biomarkers that would display prognostic superiority over HDL-C. Cell surface ecto-F1-ATPase contributes to several athero-protective properties of HDL, including reverse cholesterol transport and vascular endothelial protection. Serum inhibitory factor 1 (IF1), an endogenous inhibitor of ecto-F1-ATPase, is an independent determinant of HDL-C associated with low risk of coronary artery disease (CAD). This work aimed to examine the predictive value of serum IF1 for long-term mortality in CAD patients. Its informative value was compared to that of HDL-C.MethodSerum IF1 levels were measured in 577 male participants with stable CAD (age 45–74 years) from the GENES (Genetique et ENvironnement en Europe du Sud) study. Vital status was yearly assessed, with a median follow-up of 11 years and a 29.5 % mortality rate. Cardiovascular mortality accounted for the majority (62.4 %) of deaths.ResultsIF1 levels were positively correlated with HDL-C (rs = 0.40; P < 0.001) and negatively with triglycerides (rs = −0.21, P < 0.001) and CAD severity documented by the Gensini score (rs = −0.13; P < 0.01). Total and cardiovascular mortality were lower at the highest quartiles of IF1 (HR = 0.55; 95 % CI, 0.38–0.89 and 0.50 (0.28–0.89), respectively) but not according to HDL-C. Inverse associations of IF1 with mortality remained significant, after multivariate adjustments for classical cardiovascular risk factors (age, smoking, physical activity, waist circumference, HDL-C, dyslipidemia, hypertension, and diabetes) and for powerful biological and clinical variables of prognosis, including heart rate, ankle-brachial index and biomarkers of cardiac diseases. The 10-year mortality was 28.5 % in patients with low IF1 (<0.42 mg/L) and 21.4 % in those with high IF1 (≥0.42 mg/L, P < 0.02).ConclusionsWe investigated for the first time the relation between IF1 levels and long-term prognosis in CAD patients, and found an independent negative association. IF1 measurement might be used as a novel HDL-related biomarker to better stratify risk in populations at high risk or in the setting of pharmacotherapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0672-9) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study

Genoux

Lichtenstein

Ferrières

et al. 2016

BMC Med

View full text Add to dashboard Cite

show abstract

“…Currently, it is not clear whether the action of HDL in mediating reverse cholesterol transport is best represented by HDL cholesterol concentration, particle number, size, or some estimate of both (49). Recently, Qi et al (50) suggested that the ratio of HDL cholesterol to HDL particle number is a better predictor of HDL function than either index alone. In a human cohort FIGURE 4 Serum lipoprotein response in pups from dams supplemented with CH or CH/PS during gestation/lactation.…”

Section: Discussionmentioning

confidence: 99%

Maternal Phytosterol Supplementation during Pregnancy and Lactation Modulates Lipid and Lipoprotein Response in Offspring of apoE-Deficient Mice

Rideout

Movsesian

Tsai

et al. 2015

The Journal of Nutrition

View full text Add to dashboard Cite

show abstract

“…This suggests that cholesterol-overloaded HDL particles may have impaired atheroprotective properties and therefore that HDL subclasses differing in size or density may have differential associations with clinical outcomes. 7,11 …”

Section: Introductionmentioning

confidence: 99%

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort

et al. 2016

View full text Add to dashboard Cite

Background and Aims Recent failures of HDL cholesterol (HDL-C)-raising therapies to prevent cardiovascular disease (CVD) events have tempered the interest in the role of HDL-C in clinical risk assessment. Emerging data suggest that the atheroprotective properties of HDL depend on specific HDL particle characteristics not reflected by HDL-C. The purpose of this study was to determine the association of HDL particle concentration (HDL-P) and HDL subclasses with mortality in a high-risk cardiovascular population and to examine the clinical utility of these parameters in mortality risk discrimination and reclassification models. Methods Using nuclear magnetic resonance spectroscopy, we measured HDL-P and HDL subclasses in 3972 individuals enrolled in the CATHGEN coronary catheterization biorepository; tested for association with all-cause mortality in robust clinical models; and examined the utility of HDL subclasses in incremental mortality risk discrimination and reclassification. Results Over an average follow-up of eight years, 29.6% of the individuals died. In a multivariable model adjusted for ten CVD risk factors, HDL-P [HR, 0.71 (0.67-0.76), p= 1.3e-24] had a stronger inverse association with mortality than did HDL-C [HR 0.93 (0.87-0.99), p=0.02]. Larger HDL size conferred greater risk and the sum of medium- and small-size HDL particles (MS-HDL-P) conferred less risk. Furthermore, the strong inverse relation of HDL-P levels with mortality was accounted for entirely by MS-HDL-P; HDL-C was not associated with mortality after adjustment for MS-HDL-P. Addition of MS-HDL-P to the GRACE Risk Score significantly improved risk discrimination and risk reclassification. Conclusion HDL-P and smaller HDL subclasses were independent markers of residual mortality risk and incremental to HDL-C in a high-risk CVD population. These measures should be considered in risk stratification and future development of HDL-targeted therapies in high-risk populations.

show abstract

Cholesterol-Overloaded HDL Particles Are Independently Associated With Progression of Carotid Atherosclerosis in a Cardiovascular Disease-Free Population

Cited by 82 publications

References 27 publications

Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study

Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study

Maternal Phytosterol Supplementation during Pregnancy and Lactation Modulates Lipid and Lipoprotein Response in Offspring of apoE-Deficient Mice

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort

Contact Info

Product

Resources

About