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Double Trouble: HTN plus Dyslipidemia Aggressive Management in Primary Care

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  1. Double Trouble: HTN plus DyslipidemiaAggressive Management in Primary Care Amelie Hollier, DNP, FNP-BC, FAANP Advanced Practice Education Associates

  2. Fatty Streak • Intracellular lipids and extracellular deposits make up the fatty streak • Macrophages are part of the inflammatory process • They absorb lipids and are called foam cells • Foam cells are the hallmark of early atheroma • Just expands!

  3. How can we slow down or stop this process?

  4. Manage Risk Factors • Dyslipidemia • Hypertension • Smoking • Diabetes (a disease of endothelial dysfunction) • Elevated serum CRP

  5. The ACC/AHA 2013 HEADLINES Who Benefits from a Statin? • History of CHD or stroke (secondary prevention of ASCVD) • Patients with LDL >190 mg/dL ASCVD=atherosclerotic cardiovascular disease Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.

  6. The ACC/AHA 2013 HEADLINES Who Benefits from a Statin? • DM (no evidence of ASCVD), 40-75 years old with LDL 70-189 mg/dL • Patients (without evidence of ASCVD or DM) with LDL 70-189 mg/dLPLUS estimated 10 year risk of ASCVD > 7.5% Circulation. 2013 NovStone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.

  7. Pooled Cohort Equations CV Risk Calculator • Framingham Risk Score (FRS) had always been the standard • http://my.americanheart.org/cvriskcalculator (spreadsheet) • Many available for free download for Apple and for Android products Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.

  8. Pooled Cohort Equations CV Risk Calculator • Big CRITICISM of risk calculator is that it OVERESTIMATES patient risks (compared to Framingham) Ridker,P. Cook, N. (2013). Lancet, Opinion, Nov. 19, 2013.

  9. Pooled Cohort Equations CV Risk Calculator • 2 MDs calculated the 10 year risk of CV events using the new risk calculator in Women’s Health Study (WHS), Physicians Health Study (PHS), and Women’s Health Initiative Observational Study (WHI-OS) • New risk calculator overestimated risk by 75-150% Ridker,P. Cook, N. (2013). Lancet, Opinion, Nov. 19, 2013.

  10. Underestimates Risk??? 40 year old white male, non-smoker, no DM, systolic BP =120 Father died of AMI 45 years old Total Cholesterol: 310 mg/dL HDL: 50 mg/dL LDL: 180 mg/dL Calculated 10 yr risk = 2.4%

  11. What if your patient doesn’t fit into one of these 4 groups? 40 year old white male, non-smoker, no DM, systolic BP =120 Father died of AMI 45 years old Total Cholesterol: 310 mg/dL HDL: 50 mg/dL LDL: 180 mg/dL Calculated 10 yr risk = 2.4%

  12. What if your patient doesn’t fit into this group? “Additional factors can be taken into consideration” • LDL > 160 mg/dL or genetic hyperlipidemia • ASCVD in male FDR prior to age 55 years • ASCVD in female FDR prior to 65 years • hsCRP> 2 mg/dL • ABI < 0.9 • Elevated lifetime risk of ASCVD • Elevated calcium score

  13. Guidelines Controversy Abandonment of the LDL Targets (Goals: LDL < 100 mg/dL LDL < 70 mg/dL) • Randomized, controlled clinical trials demonstrated benefit using specific statin doses---NOT achieving LDL targets • Recommendation: Continue to measure LDL levels but don’t target specific numbers

  14. What Drug Class to Reduce Risks? • Statins are FIRST choice! • Statins are ONLY class to demonstrate reductions in mortality in primary and secondary prevention • Non-statins?

  15. “High Risk” Groups Profit from 50% or > reduction in LDL with statin • Secondary prevention in adults < 75 years • Primary prevention in adults with LDL > 190 mg/dL • Primary prevention in adults 40-75 years with LDL 70-189 mg/dL PLUS estimated ASCVS risk of > 7.5% • Primary prevention in DM 40-75 years of age with LDL 70-189 mg/dL PLUS estimated ASCVD risk of > 7.5% (Level C) Level C=consensus or expert opinion Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.

  16. Statins for “High Risk” Groups Recommendation: Need LDL reduction of 50% or greater, use: * 40 mg if 80 mg not tolerated Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.

  17. Statin CYP 450 Effect

  18. “Moderate Risk” Groups Profit from 30-49% reduction in LDL with statin • Secondary prevention in adults > 75 years old • Primary prevention in adults 40-75 years with LDL 70-189 mg/dLPLUS estimated ASCVS risk of > 7.5% (could use high dose) • Primary prevention in DM 40-75 years of age with LDL 70-189 mg/dLPLUS estimated ASCVD risk of > 7.5% (Level A) Level A=High quality RCT, high quality meta-analysis Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.

  19. “Moderate Risk” Groups Profit from 30-49% reduction in LDL with statin Circulation. 2013 Nov.

  20. CYP 450 Effect

  21. If a patient is intolerant of a moderate or high dose of a statin, OK to use a low dose statin. Take Home Point: Get the patient on a statin!

  22. Monitoring Statin Therapy Recommendation: Ask about any pre-existing muscle symptoms PRIOR to starting statin Circulation. 2013 Nov.

  23. Statin Tolerability • Myopathic syndromes: myalgias => rhabdo • Myalgias can occur WITHOUT elevations is serum creatinine kinase • Rhabdo UNCOMMON! (<0.1%) • Frequency of myalgias: 2-11% • Begin weeks to months after starting statins • Least problematic: pravastatin, fluvastatin, rosuvastatin

  24. Possible Etiologies • Inhibition of Coenzyme Q10 production • Decreased cholesterol content in muscle cell membranes

  25. Coenzyme Q-10 • Made by humans every day • Cofactor in several metabolic pathways • Ingested in fish, meats, soybean oil • Anti-oxidant • Stains impair your ability to make Coenzyme Q-10

  26. Myalgias: Other thoughts • Consider rosuvastatin or atorvastatin M-W-F or Tues or Thurs • Check lipids on M-W-F if statin 3 times weekly • Don’t forget to check Vitamin D levels (this can cause muscle pain)

  27. Monitoring Statin Therapy • Check ALT (alanine aminotransferase) at baseline. Repeat only if symptoms of hepatotoxicity occur. Circulation. 2013 Nov.

  28. Statins 2012: Removal of routine monitoring of liver enzymes from statin drug labels

  29. Statins • FDA conducted 5 previous post-market reviews between 2000 and 2009 • Finding: Statin-associated serious liver injury was extremely low • “we conclude that statin-associated severe liver injury is an extremely rare event and appears to be largely idiosyncratic”

  30. Statins • FDA Recommendation: “perform liver enzyme tests before the initiation of statin therapy (as a baseline) and as clinically indicated thereafter” • Stop statin if ALT 3 times upper limits of normal

  31. Monitoring Statin Therapy • Recheck lipid panel 4-12 weeks after statin initiated, then every 3-12 months • If LDL < 40 mg/dL on 2 consecutive measurements, reduce statin dose Circulation. 2013 Nov.

  32. Monitoring Statin Therapy • “Monitor for new-onset diabetes” Circulation. 2013 Nov.

  33. Another Label Change Feb. 2012 • FDA issued new labeling changes for the entire statin drug class • All must carry a warning about reports of increased blood sugar and A1c with statin use

  34. Pravastatin • WOSCOPS: West of Scotland Coronary Prevention Study • 30% decrease in the incidence of DM in patients taking pravastatin

  35. Type 2 Diabetes Statins associated with increased risk of NOD (new onset DM) in patients with 2-4 risk factors for DM No increased risk of NOD in patients with low risk of DM Journal of American College of Cardiology, Jan. 2013

  36. What if you can’t reach % reduction with statin? • Reinforce lifestyle changes • Look for a secondary cause

  37. What if you can’t reach % reduction with statin? Non-Statins??? “Don’t routinely use non-statins”

  38. Ezetimibe Cholesterol absorption inhibitors • Can be combined with a statin • ENHANCE trial: Reductions in LDL and increases in HDL, BUT……..

  39. Ezetimibe ENHANCE Trial • Simvastatin plus ezetimibe vs. simvastatin • No change in primary outcome (carotid intima-media thickness)

  40. Hypertriglyceridemia When Trigs > 500 mg/dL • Goal is to prevent pancreatitis by lowering trigs • Once trigs < 500 mg/dL, address LDL goal! Use a statin! • Reduction of cardiovascular risks!

  41. Hypertriglyceridemia Management • Trigs 150-199 mg/dL: Weight reduction, increased physical activity • Trigs 200-499 mg/dL: Attack LDL first, then trigs • Trigs >500 mg/dL: prevent pancreatitis first with non-pharm plus meds. When below 500 mg/dL, address LDL!

  42. Hypertension Management Critical in preventing ASCVD!

  43. Unless you’ve been in a cave… 2014 Evidence Based Guideline for management of high blood pressure in adults: report from panel members appointed to the Eight Joint National Committee E-published in Dec, 2013 James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014; 311:507.

  44. JNC 8 Guidelines • Controversial! • ACC/AHA released a statement: Anticipate new guideline in 2015 Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.

  45. 2013: American Society of Hypertension and International Society of Hypertension Wasn’t controversial! Expert Opinion ASH/ISH Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Societyof Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich) 2013 Dec 17. doi: 10.1111/jch.12237. [Epub ahead of print].

  46. JNC 8 Guidelines • Evidence Based (different from JNC 7) • Lead author, Dr. Paul James, “we wanted to make the message very simple” • 14 pages (vs. 51 pages for the lipids) Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.

  47. “Consensus” Lifestyle Changes (evidence based) • Healthy Eating Habits (Mediterranean diet?) • Limit Na intake to 2400 mg daily • Stop smoking • Achieve healthy weight • Regular physical activity

  48. JNC 8: BP by Age Start Pharmacotherapy* if BP exceeds: *Continue lifestyle changes Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.

  49. JNC 8: Patients with Diabetes • < 140/90 mmHg • Evidence Level A (high quality RCTs) • Unproven clinical benefit to lower BPs more than 140/90 Curb JD, Pressel SL, Cutler JA, et al. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group. JAMA 1996;276:1886-92. Tuomilehto J, Rastenyte D, Birkenhager WH, et al. Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators. N Engl J Med 1999;340:677-84. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703-13. ACCORD Study Group, Cushman WC, Evans GW, et al. Effects of intensive blood pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-85.

  50. American Diabetes Association • BP Goal < 140/80 mmHg • ACCORD: Intensive BP lowering did not result in reduced risk of fatal or non-fatal CV events in adults with Type 2 DM who were at high risk of these events (and they had more side effects related to intensive treatment) ACCORD Study Group, Cushman WC, Evans GW, et al. Effects of intensive blood pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-85.