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ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH INCIDENT CARDIOVASCULAR EVENTS IN WOMEN, BY LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND APOLIPOPROTEIN B100 LEVELS ANNALS OF INTERNAL MEDICINE DECEMBER 2011 Gail Wiley D.O. Candidate GA-PCOM July 2012

ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH INCIDENT CARDIOVASCULAR EVENTS IN WOMEN, BY LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND APOLIPOPROTEIN

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Page 1: ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH INCIDENT CARDIOVASCULAR EVENTS IN WOMEN, BY LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND APOLIPOPROTEIN

ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH INCIDENT CARDIOVASCULAR EVENTS IN WOMEN, BY LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND APOLIPOPROTEIN B100 LEVELSANNALS OF INTERNAL MEDICINEDECEMBER 2011

Gail Wiley

D.O. Candidate

GA-PCOM

July 2012

Page 2: ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH INCIDENT CARDIOVASCULAR EVENTS IN WOMEN, BY LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND APOLIPOPROTEIN

Funding

Merck and Co., National Heart, Lung and Blood Institute, National Cancer Institute, National Institutes of Health

Page 3: ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH INCIDENT CARDIOVASCULAR EVENTS IN WOMEN, BY LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND APOLIPOPROTEIN

Background/ Objective:

studies have shown that high levels of HDL have a anti-atherogenic effect and LDL and has an atherogenic effect

HDL particles are able to remove cholesterol from within atheromas and transport it back to the liver for excretion or re-utilization

Does HDL still have this cardioprotective effect in women at all levels of LDL and apolipoprotein B100?

apo B100 is value measuring all LDL’s (inlcluding VLDLS and intermediate density LDL’s), which are also atherogenic

study focuses particulary on women -answers questions not answered by the Framingham study

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Why is this important?

CAD remains the number one cause of death in american women

LDL has been a target of therapy for prevention of CAD (statins), HDL receiving more attention and it is still unclear wether it should be a clinical focus for treatment

 "Although clinical trial results suggest that raising HDL will reduce risk, the evidence is insufficient to specify a goal of therapy. Furthermore, currently available drugs do not robustly raise HDL cholesterol.“-quote from Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults

HDL currently used to determine CAD risk (ie Framingham tables) but low values are not routinely treated

Page 6: ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH INCIDENT CARDIOVASCULAR EVENTS IN WOMEN, BY LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND APOLIPOPROTEIN

Study Design and Setting:

prospective cohort study

participants were apparently healthy female health care professionals, age 45 or older

27,000 women were followed for a mean of 11 years

baseline lipid measurements were done at the start of study

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Endpoints included in analysis:

myocardial infarction stroke percutaneous coronary intervention coronary artery bypass grafting death from cardiovascular causes

Page 8: ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH INCIDENT CARDIOVASCULAR EVENTS IN WOMEN, BY LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND APOLIPOPROTEIN

Exclusions:

women with self-reported CAD or cancer

women on lipid lowering medications

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Results:

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cont.

Page 11: ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH INCIDENT CARDIOVASCULAR EVENTS IN WOMEN, BY LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND APOLIPOPROTEIN

Conclusion:

This study confirms the inverse relationship between HDL cholesterol and adverse cardiovascular events in women.

HDL is cardioprotective in women with all levels of LDL- high or low

HDL is cardioprotective in women with moderate to increased apo-B (measure of all “bad fats”)

study could not determine wether HDL was cardioprotective in women with very low levels apoB- very few events occured

protective effect of HDL plateaus at a level of 67 mg/dL

HDL levels have little value in predicting stroke

Page 12: ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH INCIDENT CARDIOVASCULAR EVENTS IN WOMEN, BY LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND APOLIPOPROTEIN

Limitations:

study population was healthy women- unable to predict wether HDL is protective in women with pre-existing CAD

only one baseline lipid measurement was obtained

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Comments:

This study did a good job of highlighting the interaction between “good” and “bad” fats, demonstrating why the LDL to HDL ratio of better predictive value than LDL alone.

Study also highlighted a need for there to be more research done on the relationship between cholesterol and stroke- only a weak correlation has been shown.

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Sources:

Mora S et al. Association of high-density lipoprotein cholesterol with incident cardiovascular events in women, by low-density lipoprotein cholesterol and apolipoprotein B100 levels: A cohort study. Ann Intern Med 2011 Dec 6; 155:742. 

Rafael Carmena, MD; Patrick Duriez, PhD;  Jean-Charles Fruchart, PhD (2003, February 3 Atherosclerosis: Evolving Vascular Biology and Clinical Implications. Retrieved July 15, 2012, from http://circ.ahajournals.org/content/109/23_suppl_1/III-2.full#abstract-1

Vibhuti N Singh, MD, MPH, FACC, FSCAI. Low HDL Cholesterol (Hypoalphalipoproteinemia) Treatment & Management (2002). Retrieved July 15 2012, from http://emedicine.medscape.com/article/127943-treatment

Jamaluddin Moloo, MD, MPH (Jan 19,2012) Association of Lipid Subfractions and Cardiovascular Events in Women. Retrieved July 15,2012 from http://general-medicine.jwatch.org/cgi/content/full/2012/119/2