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56 Year Old Male with Familial Hypertriglyceridemia and Hypertension

56 Year Old Male with Familial Hypertriglyceridemia and Hypertension. Case Category: Primary Prevention, Familial Hypertriglyceridemia

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56 Year Old Male with Familial Hypertriglyceridemia and Hypertension

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  1. 56 Year Old Male with Familial Hypertriglyceridemia and Hypertension Case Category: Primary Prevention, Familial Hypertriglyceridemia History of present illness: 56 year old male with extended history of high triglycerides (>1000 less than 6 months ago) and pancreatitis requiring hospitalization in past. Treatment with Tricor and Lovaza has had little effect. Has also tried Lipitor, Zeita, Niaspan and metformin but all with side effects. On a high carb, low fat diet.

  2. Patient Information

  3. Patient History

  4. Current Medications

  5. Labs Worth Noting on Tricor 145, Atenolol 50 and Lovaza 4 g

  6. Questions to Consider • Question 1: Always need to rule out secondary causes of high triglycerides, including current medications (Atenolol). Insulin resistance, diabetes, hypothyroidism? High carb diet? Alcohol use? • Question 2: Assess medication compliance. Call pharmacy to make sure medications are filled monthly, etc. • Question 3: What were the specific issues with previous drug therapies? Which statin and which dose? How severe were the side effects? Regarding Niaspan, was it taken with aspirin, food, etc.?

  7. Labs on onTricor 145, Atenolol 50 and Lovaza4 (1 of 3)

  8. Labs on onTricor 145, Atenolol 50 and Lovaza4 (2 of 3)

  9. Labs on onTricor 145, Atenolol 50 and Lovaza4 (3 of 3)

  10. NMR LipoProfile • Insert NMR Lipoprofile 06152011 MC54 Insert

  11. Other Labs on onTricor 145, Atenolol 50 and Lovaza 4

  12. Initial Treatment & Management • Advise low carb diet, increased exercise and to specifically avoid sugary beverages and alcohol. • Consider stopping fenofibrate due to apparent lack of efficacy, borderline high creatinine and low HDL. For now continue. • Continue Lovaza 4 g/day. • Start Glumetza (metformin ER 500 mg) 2-3 tablets daily with slow titration as tolerated. Brand name is better tolerated and he is concerned about GI side effects. • Consider switching from Atenolol to Carvedilol (generic BID or Coreg CR once daily). Carvedilol a is beta blocker that is lipid neutral. • Advise home blood pressure meter and switching to a beta blocker that does not affect lipids. • Treat secondary causes for myalgia (vitamin D deficiency). Also consider CO Q 10 supplement with ubiquinol; Effective dose is 300-600 mg/day in capsules with oil. This is in anticipation we may need to add statin. • Start Vitamin D3 5000 IU for 8 weeks and Vitamin D2 50000 IU/week. Addressing deficiency will help muscle aching if a statin is needed for hypertriglyceridemia.

  13. Discussion (1 of 4)

  14. Discussion (2 of 4)

  15. Discussion (3 of 4)

  16. Discussion (4 of 4)

  17. 4 Month Follow Up on Tricor 145, Atenolol 50, Glumetza1000, Lovaza 4 and Vitamin D3 5000 (1 of 6)

  18. 4 Month Follow Up on Tricor 145, Atenolol 50, Glumetza 1000, Lovaza 4 and Vitamin D3 5000 (2 of 6)

  19. 4 Month Follow Up on Tricor 145, Atenolol 50, Glumetza 1000, Lovaza 4 and Vitamin D3 5000 (3 of 6)

  20. 4 Month Follow Up on Tricor 145, Atenolol 50, Glumetza 1000, Lovaza 4 and Vitamin D3 5000 (4 of 6) Based on sterol testing not surprising prior Zetia trial not effective

  21. 4 Month Follow Up on Tricor 145, Atenolol 50, Glumetza 1000, Lovaza 4 and Vitamin D3 5000 (5 of 6)

  22. 4 Month Follow Up on Tricor 145, Atenolol 50, Glumetza 1000, Lovaza 4 and Vitamin D3 5000 (6 of 6)

  23. NMR LipoProfile • Insert NMR Lipoprofile 09272011 MC54 Insert

  24. 4 Month Follow Up on Tricor 145, Atenolol 50, Glumetza 1000, Lovaza 4 and Vitamin D3 5000 (1 of 2) • Hypertriglyceridemia – Improved. • On Tricor 145, Lovaza 4 and Glumetza (metformin ER) 1000 mg. Only taking 1000 mg due to tolerance issues. Higher doses needed to impact triglycerides Triglycerides have lowered to 474 from 589, but still too high. • HDL is too low at 26. Apo A1 is also low possibly due to genetic inability to make HDL protein. HDL cholesterol may decrease with fenofibrate. • Advise stopping Tricor due to ineffectiveness. • Stain therapy may be an option. He has experienced muscles aches during past taking statins. He tried CO Q 10, but did not experience much benefit. There is also no evidence of hyperabsorbing on sterol testing(normal campesterol/sitosterol). Bottom line Zetia or intestinally acting agents unlikely to be of benefit. Statin more appropriate • Start Crestor 5 mg to lower triglycerides and raise HDL. Crestor is better tolerated . It is better metabolized than other alternative statins. Patients experience less muscle aches. The JUPITER clinical trial has shown 47% reduction in cardiac events in those who take Crestor. It is acceptable to take ½ a tablet if necessary. • Modify diet. Patient is still consuming too many carbs and more sugar than optimal. • Continue Lovaza 4 as omega 3 index is currently optimal >8%

  25. 4 Month Follow Up on Tricor 145, Atenolol 50, Glumetza1000, Lovaza 4 and Vitamin D3 5000 (2 of 2) • Hypertension – Deteriorated. • BP is high at 160/92. • Advise switching from Atenolol to Carvedilol due to triglyceride impact and avoid HCTZ. • Metabolic Syndrome – Unchanged. • Only taking Glumetza 1000 mg due to tolerance issues which does not impact triglycerides as much as higher doses. • Try increasing Glumetza to 1500 mg. • Start Cycloset. Cycloset can be used safely in prediabetic patients as it does not lower glucose to the extent that would cause hypoglycemia and works well to treat insulin resistance. Cycloset has beneficial effects on lipids and shown to reduce CVD events and may lower BP as well as triglycerides up to 30%. Another study showed Cycloset to reduce CVD events by 55%. • Take Cycloset 0.8 mg. Take with food within 2 hours of waking. Start with 1 tablet and gradually increase to 4-6 per day all at once and in the morning. Taking with food will minimize nausea. • Reduce carb and sugar intake.

  26. 2nd Follow Up on Glumetza 1000, Crestor 5, Cycloset 0.8 4/day, Lovaza 4 and Vitamin D3 5000 (1 of 2) • Hypertriglyceridemia – Improved. • Stopped Tricor last visit. • Started Crestor 5 mg, history of prior intolerance to other statins. Tolerating well and NOT taking CO Q 10. Also had a recent steroid injection. Try Crestor 10 mg. • Started Cycloset 0.8 mg 4/day. Tolerating well. • Taking Glumetza 1000 and Lovaza 4. • Triglycerides lowered from 474 to 284. LDL-C lowered to 22. LDL-P lowered to < 300 from 1084. • Insulin resistance improved with the addition of Cycloset. • Inflammatory markers are normal (MPO, LpPLA2, CRP). • Hypertension – Improved. • Stopped Atenolol last visit and switched to Losartan. Atenolol may have affected triglycerides. • Myalgia – Improved. • Consider CO Q 10 300-600.

  27. 2nd Follow Up on Glumetza 1000, Crestor 5, Cycloset 0.8 4/day, Lovaza 4 and Vitamin D3 5000 (2 of 2) • Metabolic Syndrome – Improved. • HbA1c is down to 5.4 from 5.5. • Glumetza 1000 mg is tolerated. • Cycloset 0.8 mg 4/day is well tolerated. • Vitamin D Deficiency – Improved. • Taking Vitamin D3 5000 mg/day. • Levels are up to 58 compared to 43 last visit and originally 22. • Homocystinemia – Improved. • Homocysteine levels decreased to 8 from 19 last visit. • Tricor can increase levels and Tricor was stopped last visit. Level is now normal.

  28. 2nd Follow-Up Labs on Glumetza 1000, Crestor 5, Cycloset 0.8 4/day, Lovaza 4 and Vitamin D3 5000 (1 of 5)

  29. Follow-Up Labs on Glumetza 1000, Crestor 5, Cycloset 0.8 4/day,Lovaza 4 and Vitamin D3 5000 (2 of 5)

  30. Follow-Up Labs on Glumetza 1000, Crestor 5, Cycloset 0.8 4/day, Lovaza 4 and Vitamin D3 5000 (3 of 5)

  31. Follow-Up Labs on Glumetza 1000, Crestor 5, Cycloset 0.8 4/day,Lovaza 4 and Vitamin D3 5000 (4 of 5)

  32. Follow-Up Labs on Glumetza 1000, Crestor 5, Cycloset 0.8 4/day, Lovaza 4 and Vitamin D3 5000 (5 of 5)

  33. NMR LipoProfile • Insert NMR Lipoprofile 01122012 MC54 Insert

  34. Clinical Pearls • Treating insulin resistance is always an option to consider as an alternative approach to a hard to treat patient with history of many drug intolerances. Pioglitazone, Metformin, Cycloset, and GLP 1 agonists all improve lipids and will not cause hypoglycemia so can be used safely in prediabetes. • Homocysteine elevations may be due to other medications (fenofibrate >>> Niacin).

  35. Case Summary

  36. References (1 of 2) • Cromwell WC, Otvos JD, Keyes MJ, et al. LDL particle number and risk of future cardiovascular disease in the Framingham offspring study – implications for LDL management. J ClinLipidol 2007 Dec;1(6):583-92.. • Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. Jul 13 2004;110(2):227-39. • Kolovou GD, Anagnostopoulou KK, Kostakou PM, et al. Primary and secondary hypertriglyceridaemia. Curr Drug Targets. Apr 2009;10(4):336-43. • McKenney JM, McCormick LS, Weiss S. A randomized trial of the effects of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia. Collaborative Atorvastatin Study Group. Am J Med. Feb 1998;104(2):137-43. • National Cholesterol Education Program. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. May 16 2001;285(19):2486-97. • Roth EM, Bays HE, Forker AD, et al. Prescription omega-3 fatty acid as an adjunct to fenofibrate therapy in hypertriglyceridemic subjects. J CardiovascPharmacol. Jul 10 2009. • Triglycerides and Cardiovascular Disease: A Scientific Statement form the American Heart Association Circulation published online Apr 18, 2011 DOI: 10.1161/CIR.0b013e3182160726 Circulation published online Apr 18, 2011;

  37. References (2 of 2) • Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011 Feb;42:517-84. • Kaplan NM. Systemic hypertension: Treatment. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 46. • Victor, RG. Systemic hypertension: Mechanisms and diagnosis. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 45. • Gaziano JM, Cincotta AH, O’Connor CM, et al. Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes. Diabetes Care. 2010 Jul;33(7):1503-8. • Pili H, Ohashi S, Matsuda M, et al. Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care 2000 Aug;23(8):1154-61.

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