1. 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

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

3. 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

5. 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

6. 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

7. Endpoints included in analysis:  myocardial infarction  stroke  percutaneous coronary intervention  coronary artery bypass grafting  death from cardiovascular causes

8. Exclusions:  women with self-reported CAD or cancer  women on lipid lowering medications

9. Results:

10. cont.

11. 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

12. 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

13. 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.

15. 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