Lipoprotein(a): An Inherited Disorder

A 58-year-old previously healthy African-American man presented to the hospital while traveling with severe abrupt onset epigastric and chest pain, diaphoresis and nausea with ST elevation in the inferior leads and diffuse reciprocal ST depressions on initial ECG. He underwent acute coronary angiography demonstrating diffuse noncritical stenosis of the left anterior decending (LAD), high grade disease in the mid left circumflex (LCx) and acutely occluded right coronary artery (RCA) with staining thrombus in the proximal third of the vessel. He was successfully treated with drug eluting stents to the RCA and LCx. He evolved a troponin I elevation to 17 ng/mL, the acute left ventricular ejection (LVEF) was 40% with inferior-posterior dense hypokinesis.

He initially did well on medical therapy for four months until presenting with two days of similar symptoms in crescendo pattern and was admitted to the hospital. There were no acute ST changes or acute changes on ECG and multiple troponin I determinations were negative. Given his history and presentation, he underwent repeat coronary arteriography showing patent stents in the RCA and LCx, but progression of disease in the mid to distal LAD now to 60-70% stenosis without evident plaque ulceration or thrombus. LVEF was 50-55% with inferior moderate hypokinesis. The LAD disease was diffuse and distal, felt unfavorable for percutaneous intervention. Medical therapy was intensified with titration of beta blocker, and addition of amlodipine and oral nitrate. Dual antiplatelet therapy and rosuvastatin 40mg were continued.

Family history was notable for a sister with coronary disease having coronary bypass surgery at age 60 without conventional risk factors. His mother, age 87, is essentially healthy but his father died in his 50’s from myocardial infarction. He has five adult children under the age of 30 who are alive and well.

His personal history is notable for the lifelong absence of conventional cardiovascular risk factors. He exercises on a rigorous schedule and has done so for his entire adult life. He is trim and athletic with normal body weight. Physical examination was entirely normal.

His initial laboratory studies showed total cholesterol 132, HDL-C 44, non-HDL-C 88, Friedewald estimated LDL-C 73 and triglycerides 73 mg/dL. Fasting glucose was 110 mg/dL. BUN and creatinine were normal. Lipoprotein(a) was elevated, 292 nmol/L (normal value <75 nmol/L); hsCRP was <0.2 mg/L.

He had no further symptoms and was discharged from the hospital.

Additional data following discharge:

Treadmill SPECT MPI: no ischemia in LAD territory at 91% age adjusted predicted heart rate.

Six months post discharge on 40 mg/day rosuvastatin:

Apolipoprotein B:  87 mg/dL (slightly less than 50th population percentile)
Apolipoprotein AI: 169 mg/dL

Two hour glucose tolerance test: normal (98 mg/dL)
Hemoglobin A1C: 5.9%

Non-HDL-C: 77 mg/dL (<10th population percentile)

Directly measured Friedewald-equivalent LDL-C by ultracentrifugation:
= (Biologic LDL-C  +  Lp(a)-C  +  IDL-C)

  • Biologic LDL-C:  48 mg/dL, distributed primarily in small dense LDL fractions
  • Lp(a)-C: 12 mg/dL
  • IDL-C:  5 mg/dL

=65 mg/dL.

What plans should be made for further management post discharge?

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