4/14/2018 DYSLIPIDEMIA CASES. Mary Malloy, MD. I have nothing to disclose

Transcription

1 DYSLIPIDEMIA CASES Mary Malloy, MD I have nothing to disclose 1

2 Case 1 A 24 year old healthy, slender woman is referred because she has a family history of premature CAD (mother, age 59, had onset of angina at 53). Patient s diet and exercise habits are exemplary. Her lipid panel reveals the following: Total cholesterol 236 Triglycerides 120 HDL-C 52 LDL-C 160 Thyroid and liver function tests are normal Physical exam is normal Case 1, cont. What additional information would you like to have about her mother? What other lab tests would you order? Would a measure of arterial stiffness (bapwv) be useful in risk assessment of this patient? What diagnosis would you consider if she had no family history of premature CVD and her parents lipids were normal? 2

3 Mother s risk factors: social smoker high cholesterol; normal triglycerides started statin late at age 53 Her father required CABG at age 47 (smoker) Case 1, cont. What additional information would you like to have about her mother? What other lab tests would you order? Would a measure of arterial stiffness (bapwv) be useful in risk assessment of this patient? What diagnosis would you consider if she had no family history of premature CVD and her parents lipids were normal? 3

4 Additional lab test results: Lipoprotein (a) not elevated LpPLA2 borderline high Would you want to do genetic testing? Case 1, cont. What additional information would you like to have about her mother? What other lab tests would you order? Would a measure of arterial stiffness (bapwv) be useful in risk assessment of this patient? What is her likely diagnosis? What diagnosis would you consider if she had no family history of premature CVD and her parents lipids were normal? 4

5 Case 1, cont. This patient likely has HeFH on the basis of her lipid phenotype and that of her mother, and her family history of premature CAD. Primary preventive statin Rx was discussed. She was about to be married and wanted to start a family soon. She elected to postpone treatment. Case 2 A 56 year old woman is referred by neurology for assessment of risk factors that may have contributed to her recent thrombotic stroke. You find that she has normal lipid and coagulation panels aside from an Lp(a) level that is 3 times normal and a minimally elevated level of homocysteine. Would you try to reduce her Lp(a)? What other treatment might you suggest? 5

6 Case 2, cont. You recall seeing another patient with an elevated level of Lp(a), that one approaching 5 times normal, who was asymptomatic for CVD at age 76. What might explain the lack of evidence of arterial disease in that person? What non-genetic factors can cause elevated levels of Lp(a)? IL-1β, Lp(a), and Risk of CVD Proinflammatory Interleukin-1 genotypes can modulate long-term effects of Lp(a) on cardiovascular events This may explain why some patients with elevated Lp(a) are at higher risk Targeting IL-1β decreased CVD events (Cantos) 6

7 Case 3 An 18 year old male presents with large Achilles tendon xanthomas and an LDL-C of 386 mg/dl. Triglycerides and HDL-C are normal. His primary MD suspected FH but the patient was mutation-negative. He was referred for diagnosis and management. What might be his diagnosis? Case 3, cont. On exam you notice some small tuberous xanthomas on his elbows. Would this change your impression? 7

8 Differential Diagnosis Case 3 Double heterozygote for FH (mutation in two genes) Compound heterozygote for FH (different mutations in the same gene) Phytosterolemia 8

9 Case 4 A 26 year old Asain woman had a first cholesterol screen at a health fair. The level was 325 mg/dl. She has been well, is not overweight, and avoids high fat foods. She seldom drinks alcohol. She is adopted and her birth parents health histories are unknown. What questions would you like to ask her? How would you evaluate this patient? Case 4, cont. Lipid panel results: TC 295; TG 870; HDL-C 39; direct LDL-C 98; Lp(a) 31 nm/l What other lab tests would you order? What is the DDX? How would you manage this patient? 9

10 Case 4, cont. Additional tests ordered: Plasma albumin normal Urinary protein negative A1C 5.4% Autoimmune tests normal Case 4, cont. DDX: A genetic hypertriglyceridemia likely Apo A-V deficiency (she is Asian) Management: Low fat, low simple CHO diet Fish oil/fibrate 10

11 Case 5 An opthalmologist diagnosed a Hollenhorst plaque in a 30 year old male and refers him to you for evaluation. Do you consider this an urgent referral? What laboratory or other tests will you order? 11

12 Hollenhorst Plaque Refractile cholesterol emboli located at arteriole bifurcations in the retina Emboli thought to originate most often from carotid (or aortic arch) atheromata About 75% are asymptomatic About 25% associated with carotid stenosis; may require endarterectomy Predict CVD mortality; stroke risk Case 5, cont. Labs to include Lp(a); lipid panel; A1c Carotid ultrasound Consider stroke risk factors Note urgent nature of problem in medical record if patient wishes to delay evaluation Start ASA (possibly other anticoagulant) 12

13 Case 6 A 46 year old woman has HeFH. You decide to reduce her LDL-C with a statin. She discontinues it after about 5 months because of some muscle aching in her arms. What questions would you want to ask her to determine whether the symptoms are related to the statin? If you think they are related, what will do next? Rare Features: Autoimmune Myopathy Muscle symptoms prominent and continue long after the statin is stopped Persistently high CK Positive HMGCR antibodies Can occur in absence of statin Rx Rx: Immunosupressant regimen (long term) 13

14 Case 7 A 45 year old man had a myocardial infarction at age 43. His lipid panel and Lp(a) were normal except for an LDL-C of 147 mg/dl. Coronary angiography revealed severe 3 vessel disease requiring bypass surgery. Full dose statin was prescribed. He recently was found to have near occlusion of another native vessel. Case 7, cont. He is a never smoker, had lifelong good diet and exercise habits, and is not diabetic or hypertensive. He has an impressive family history of premature MI including his father, maternal grandmother, and 2 paternal uncles. What may have led to his severe disease? 14

15 Emerging Mechanisms of CAD Impaired efflux of cholesterol from the artery wall importance of measuring Prebeta-1 HDL New genetic determinants: VAMP8, KIF6, MYH15, PALLD, SNX19 Dysfunctional HDL Elevated cytokine transport by HDL Thrombogenic disorders 15