Low HDL-levels: leave it or treat it?

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Holly Sherman
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1 Cardiology Update 2011 Davos, Low HDL-levels: leave it or treat it? Experts: J.P. Kastelein, Amsterdam and U. Landmesser, Zurich Cases: C. Besler, Zurich and I. Sudano, Zurich

2 Mr H.B., years old patient, married, has two doughter, 19 and 15 y.o. and is working as bank director. He would like to assess his cardiovascular risk as his father had the first myocardial infarction around his actual age.

4 Mr H.B., 1960 Family History Grandfather (father) died at age of 57 y.o. for a myocardial infarction Grandfather (mother) diabetic, hypertensive, died at age of 67 for a stroke. He had previous TIA/Stroke at age of 52 and 60. Father, 74 y.o. had a first MI at the age of 49 J. and the second at the age of 55; RF smoking and high cholesterol, Mother, 70 y.o., diabetic (oral therapy), overweight and treated for dyslipidemia since she is in menopause; an older sister, 47 with diagnosis of coronary heart disease (2 vessels-disease), a younger sister, 40 y.o. healthy.

5 Mr H.B Mr H.B. is born and is living in Germany He is smoking cigarette/day since he was 15 y.o. He was regularly playing football till he get married (20 years ago), after he did make any regular physical activity and he gain around 20 Kg He drinks regularly alcohol (2 Glas Wine or 2-3 Bier for dinner) and he is eating at least once a day in a restaurant. Patient refers no symptoms; he feels well. To the question what happen when you exercise? he answers that he fells out of form

6 Mr H.B., cm, 104 kg, Waist circumference: 109cm BP sitting 138/86 mmhg (right), 136/84 mmhg (left), BP standing 136/82 mmhg (right) Heart rate 72/min sitting, Physical examination: ndn

7 Mr H.B., 1960 Creatinine 78 mmol/l GFR (MDRD) 66 ml/min Potassium 3.7 meq/l Fasting Glucose 118 mg/dl Total Chol. 273 mg/dl HDL 25 mg/dl LDL 191 mg/dl TG 286 mg/dl TC/HDL CRP 0.8 mg/dl Urin ndn

8 How high is the cardiovascular risk of this patient? 1. Less than 10% 2. 10% 3. 20% 4. More than 20%

10 What should we suggest to Mr H.B.? 1. Life Style changes (stop smoking, weight reduction, nutritional changes, physical activity) for 1 month before prescribing a therapy 2. Life Style changes (stop smoking, weight reduction, nutritional changes, physical activity) for 3 month before prescribing a therapy 3. Life Style changes + Statin 4. Life Style changes + Statin + Aspirin

12 Aspirin for primary prevention in high risk patients?

13 Mr H.B., month later He stop smoking since 2 weeks, his weight is stable He paid for a fitness club, but he went there twice Therapy: statin and aspirin (100 mg) since 1 month Total Chol. 214 mmol/l HDL 28 mmol/l LDL 141 mmol/l TG 210 mmol/l TC/HDL 7.6 AST 37 U/L CK 69 U/L

14 Primary prevention in patients with high cardiovascular risk... Low HDL-Cholesterol: should we treat or forget it?

15 Sacks FM, Am J Cardiology, 2002 Ridker PM et al, Circulation 1998 HDL and CAD risk

16 HDL and CAD risk

Framingham Study 100 mg/l 2.6 mmol/l 160 mg/l 4.1 mmol/l LDL-C 220 mg/l 5.

18 Low HDL-C is an independent predictor of CHD risk even when LDL-C is low Risk of coronary heart disease over 4 years of follow-up for men ages 50 to 70 Data from Framingham Study 100 mg/l 2.6 mmol/l 160 mg/l 4.1 mmol/l LDL-C 220 mg/l 5.7 mmol/l 25 (0.6 mmol/l) 45 (1.2) 65 (1.7) 85 mg/l 2.2 mmol/l Gordon T et al. Am J Med. 1977;62:707

19 Ridker Pm et al, Lancet 2010

20 Lifestyle interventions & HDL mg/dl mmol/l Changes in HDL-cholesterol moderate alcohol physical activity cigarette smoking women men

21 Smoking cessation and HDL Gepner AD et al, Am Heart J 2011;161:145-51

22 Change in HDL induced by weight loss Dattilo Am et al, Am J Clin Nutr 1992 The Look AHEAD Research Group Arch Intern Med. 2010

23 Physical activity and HDL increase Curtis Ellison R al., Am Heart J 2004

24 Alcohol intake and HDL cholesterol Curtis Ellison R al., Am Heart J 2004

25 HDL as a Therapeutic Target Fibrate Statins Niacin Ezetimibe CETP- Inhibitors Omega 3 Combination Brewer NEJM 2005

26 Lin Y et al, 2010

27 Fibrate and cardiovascular disease Primary prevention Lin Y et al, 2010

28 Nicotinic acid and cardiovascular disease Primary prevention Bruckert E et al, Atherosclerosis 2010

29 Besler C et al. & Landmesser U. Curr Pharmacol Des 2010, 16: HDL: proposed anti-atherogenic effects Bile VLDL/ LDL LDL-R FC 1. HDL-mediated promotion of RCT (reverse cholesterol transport) Liver CE TG CE SR-BI PLTP CETP A-I FC CE Mature HDL LCAT HDL A-I FC Nascent HDL ABCG1 ABCA1 SR-BI? Macrophage 2. Direct HDL-mediated endothelial-protective effects Anti-oxidant Effects Anti-inflammatory Effects Endothelial NO Production Endothelial Repair Anti-thrombotic Effects

30 Spieker L et al, Circulation 2002

31 Sorrentino et al, Circulation 2010

32 HDL EFFLUX CAPACITY Heinecke J, NEJM 2011

33 Is HDL more than HDL-Cholesterol? Khera AV et al, NEJM 2011

34 Mr H.B., months later He stop smoking since more than 5 months, he gained 2 Kg, Drink 1-2 Glas Wine or 1 Beer at dinner and went jogging 2 times/week Therapy: statin (high dosis) and aspirin (100 mg) Total Chol. 194 mmol/l HDL 31 mmol/l LDL 118 mmol/l TG 162 mmol/l TC/HDL 6.2 CK 69 U/L

36 Would you modify the therapy of the patient trying to increase HDL-Cholesterol? 1. No 2. Strengt Life style modification 3. Yes, I suggest Nicotinic acid 4. Yes, I suggest a fibrate 5. Yes, I suggest ezetimibe 6. Yes, I suggest Omega 3

ESC Congress 2011 Wednesday August 31st 2011

ESC Congress 2011 Wednesday August 31st 2011 ESC Congress 211 Wednesday August 31st 211 stimulates endothelial CAT-1 expression and L-arginine uptake: a novel mechanism leading to endothelial-protective effects of that is profoundly impaired in patients