1. CHRISTIAN SONNIER MD 7/15/14 Hyperlipidemia:

2. Hyperlipidemia Definition: an elevation of total cholesterol and or LDL with or without decrease in HDL.

3. Hyperlipidemia Epidemiology:  16% of US adults have total cholesterol >240mg/dL, however some estimations (AHA 2005) placed it as high as 45% of US adults  Total cholesterol >200mg/dL account for greater than 27% of heart disease in men and 34% of heart disease in women.  Women have higher prevalence of elevated total cholesterol  Men have higher prevalence of low HDL

4. Hyperlipidemia Etiology:  Primary  Single or multiple gene mutations disrupting LDL and triglyceride production or clearance  Usually in younger patients  Secondary  Disturbances due to sedentary lifestyle and diet  Associated with many different co-morbid conditions Renal disease (CKD) DM Hypothyroidism Liver disease Heart Disease

5. Hyperlipidemia Clinical manifestations  Usually asymptomatic until one of the following  Cardiovascular disease: CHF, ACS, PAD  Obesity  Diabetes Mellitus  Cholelithiasis  NAFLD: non-alcoholic fatty liver disease  Xanthelasmas  Arcus corneae

6. Hyperlipidemia Diagnosis:  Most cases of hyperlipidemia are found on screening exams  Fasting lipid panel Cholesterol, HDL and LDL-C (calculated total-HDL) and triglyceride  In order for this to work screening must be done on patients according to cardiovascular risk  Age  Sex  HTN  Smoking  Family hx of premature CAD  DM  We will cover this more later

7. Diagnosis: (fasting lipid panel)  Any deviation from the following can technically be classified as dyslipidemia however specific goals for cholesterol values depend on a few more factors which we will discuss later  Total cholesterol: 200mg/dL or less  LDL (calculated): 100 mg/dL or less  HDL: 40mg/dL or more for men  HDL : 50mg/dL or more for women  Triglycerides: 150mg/dL or less

8. Hyperlipidemia Treatment:  Lifestyle modification  Weight loss  Diet  Exercise  Per uptodate: diet alone in one UK study can reduce total cholesterol and LDL by 5-7 present  MRFIT trial: diet change and exercise resulted in decrease of 5- 10mg/dL of total cholesterol Deemed to be too small of a change to significantly alter mortality

9. Treatment:  Statin therapy:  Pravastatin: WOSCOPS trial in scotland  Lovastatin: AFCAPS/TexCAPS trial in Texas  Atorvastatin: ASCOTLLA  Rosuvastatin: JUPITER trial  We will talk about these more in a few minutes  Non-statin therapy  Niacin  Bile acid sequestrants  Fibric acid derivatives  ect

10. Hyperlipidemia: Prevention:  Good dietary habits and exercise in children and young adults  Rigorous screening and patient education  Likely would require more public outreach initiatives

11. Hyperlipidemia 2013 guidelines Following slides are a combination of the  ACC/AHA 2013 guidelines  Uptodate  Rakels “Textbook of Family Medicine”  Published results of various trials

12. Various trial results of individual statins Rosuvastatin Jupiter trial  reduced LDL cholesterol levels by 50%  reduced high-sensitivity C-reactive protein levels by 37%.  Reduced rates of MI and stroke  Did not have significant increase in myopathy or cancer  Had higher incidence in physician reported diabetes Pravastatin: WOSCOPS trial  Reduced total cholesterol by 20%  Reduced LDL by 26%  Reduction of risk of death from any cause by 22%  Treatment group had 48% less cardiovascular events than control Atorvastatin: ASCOTLLA trial  Reduced total cholesterol by 1.3mmol/L  Reported significant reduction in LDL however no % given Lovastatin: AFCAPS/TexCAPS trial  Reduced LDL by 25%  Reduced total cholesterol by 19%  Increased HDL by 6%

13. ACC/AHA 2013 Primarily studied effects of statins on HLD and identified “4 major statin benefit groups” defined as: “groups…for whom ASCVD risk reduction clearly outweighs risk”  1) clinical ASCVD  2) patients with LDL over 190mg/dL  3) DM patients 40-75 yo with LDL 70-189mg/dL and no ASCVD  4) patients without ASCVD or DM with LDL 70-189mg/dL and a 10 year risk of ASCVD over 7.5%  Clinical ASCVD is defined by acute coronary syndromes, or a history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin.

14. ACC/AHA 2013 In summary the following should be on a statin  Any vasculopath (CAD, PAD or equivalent)  Any patient with DM over age of 40 and LDL over 70  Any patient over 40 yo and risk of significant vascular event of 7.5  Basically most patients we see in the clinic….

15. HLD: putting it all together Lipid lowing therapy such as statins can lower cardiovascular risk by 20-30% alone when used appropriatly Statins are unlikely to help a patient if LDL is under 70mg/dL Any initiation of statins should be accompanied by a discussion of life style modification Before initiating a statin consult a cardiovascular risk calculator (framingham, ASCVD, ect) and decide if the benefits out weight the risks

16. Putting it all together continued Statin doses:  Most research has been done on low to moderate intensity treatment.  Therefore recommendations are to start with moderate doses  Lovastatin 40mg  Pravastatin 40mg  Simvastatin 40mg  Atorvastatin 20mg  Rosuvastatin 5-10mg

17. Putting it all together continued Monitoring treatment results:  Sources recommend f/u labs and visits q6-12 months  Can always go up on dose or change medications Side effects:  Most common effects are myalgia, myopathy and other muscular complaints  In most patients a simple change in dose or choice of statin can resolve this issue  Some patient’s may require vitamin supplementation with Q10)  In patient’s who do not tolerate statins… it is not recommended to abandon statins for non-statin lipid lowering medications.

18. Practice questions According to the US Preventative Services Task Force (USPSTF) increased risk of Coronary Heart Disease (CHD) is defined by the presence of which of the following risk factors?  A) african american  B) Hypertension  C) Diabetes  D) BMI of 30 kg/m2 or greater

19. answer B, C, D  Increased riks of CHD is defined as any of the following  Diabetes  Family hx of CHD or other equivalent  Family hx of CHD before 50 yo in male relative and 60 in female  Tobacco use  HTN  Obesity (BMI over 30)

20. Practice question John Doe is a 31 yo wm with no significant pmhx, does not drink or smoke and has a BMI of 24. John is in good health today at this visit and presents today for a preventative medicine check up. John reports a family hx of MI in his father at age 45. Physical exam is unremarkable. Labs are as follows: Cholesterol 110 mg/dL, LDL 50mg/dL, HDL 60mg/dL. Which of the following is the best next step?  A) No treatment today with f/u fasting cholesterol in 9 years  B) No treatment today however encourage John to begin life style modifications and f/u fasting lipids in 1 year  C) Begin treatment with statin of choice and life style modifications with f/u fasting lipids in 6 months  D) Immediately admit patient to hospital for emergency left heart cath.

21. answer B  The patient has an increased risk of CHD due to family history therefore you could argue that he should be started on some form of treatment. Your options are lifestyle or pharmacologic. Since he has an LDL of less than 70 mg/dL and does not fit one of the 4 major statin benefit groups he should be started on lifestyle modifications and followed closely.

22. Practice question: Jane doe is a 53 yo with a pmhx of HTN, TIA and MI in the last 3 years. She presents today for a routine check up and has no current complaints. She is currently lisinopril and HCTZ for HTN and ASA 81 mg. She has an unremarkable exam. Before going to lab today she informs you she has not fasted and will not be able to return to the clinic for 1 month to have a fasting lipid panel drawn. What is the appropriate course of action at this time?  A) begin lifestyle modification only as you have no lipid panel available  B) begin lifestyle modification as well as niacin tablets TID for the next month until you obtain a fasting lipid panel  C) begin lifestyle modification with a moderate intensity statin today.  D) fire the patient for poor compliance

23. answer C  According to the ACC/AHA 2013, you should start statins if the patient meets the following:  1) clinical ASCVD  2) patients with LDL over 190mg/dL  3) DM patients 40-75 yo with LDL 70-189mg/dL and no ASCVD  4) patients without ASCVD or DM with LDL 70-189mg/dL and a 10 year risk of ASCVD over 7.5%

24. Practice question Tyrion Lannister is a 40 yo wm with pmhx of dwarfism, severe facial laceration, and alcoholism. Presents today for routine f/u. The patient reports a diet of rich fatty foods with little to no exercise, however he managed to fast today for his am labs. Exam is unremarkable apart from short stature. The patient’s labs are as follows total cholesterol of 268 mg/dL, LDL of 195 mg/dL, HDL of 50mg/dL. Which of the following is the most appropriate next step?  A) begin patient on lifestyle modification with bile sequestrant tid  B) begin patient on lifestyle modification only  C) begin patient on lifestyle modification and moderate intensity statin therapy  D) begin patient on lifestyle modification and low intensity statin therapy due to dwarfism  E) call the city guards and have the patient escorted to see Grand Meister Tyrell for treatment.

25. answer D  According to ACC/AHA 2013 patient needs statin:  1) clinical ASCVD  2) patients with LDL over 190mg/dL  3) DM patients 40-75 yo with LDL 70-189mg/dL and no ASCVD  4) patients without ASCVD or DM with LDL 70-189mg/dL and a 10 year risk of ASCVD over 7.5%

26. Sources http://tools.cardiosource.org/ASCVD-Risk-Estimator/ afcaps/texcaps trialJAMA. 1998 May 27;279(20):1615- 22.JAMA. 1998 May 27;279(20):1615- 22. ascotlla trialLancet. 2003 Apr 5;361(9364):1149-58.Lancet. 2003 Apr 5;361(9364):1149-58. woscops trialN Engl J Med. 1995 Nov 16;333(20):1301-7.N Engl J Med. 1995 Nov 16;333(20):1301-7. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults JUPITER Study Group N Engl J Med 20, 2008DOI: 10.1056/NEJMoa080764620, 2008DOI: 10.1056/NEJMoa0807646 Uptodate: hyperlipidemia managment Rakel: Textbook of Family Medicine pg 81-83