WHEN BAD THINGS HAPPEN TO GOOD PEOPLE : CASE STUDIES

ROB GREENFIELD MD FACC FAHA FNLA

CALIFORNIA HEART ASSOCIATES

UC-IRVINE MEDICAL CENTER

DISCLOSURES

• Speaker: Sanofi

• Speaker: Regeneron

• Speaker: Amgen

CASE #142 Y/O MALE ADMITTED FOR AN ACUTE ANTERIOR MI in 2017

1- No hx for htn or diabetes. Never smoked . Never had a prior lipid panel

2- BMI 25, BP 110/70, HR 80. II/VI SEM LSB , aortic area

Lipids : TC 181 MG/DL, LDL-C 110 MG/DL, TG 115 MG/DL HDL-C 48 MG/DL

Rx: PCI stent x 2 LAD ; CIRC-OM 40-50%

D/C : Atorvastatin 80mg , Brilinta 90mg bid, metoprolol 25mg bid, ASA 81mg daily

CASE #1 2019- INFERO-LATERAL MIOne week earlier…

TC= 152 MG/DL, HDL-C 63 mg/dl,

LDL-C= 56mg/dl TG= 95mg/dl

Lp(a)= 237 nmol/L

WHY?????????????????????

Lipid Spin 2018

Lp(a) – LDL particle with an apolipoprotein (a) attached to it

The apo (a) varies in size based on the number of kringle-4 repeats

It is both pro-atherogenic and pro-thrombotic (Risk factor)

Lipid Spin • Volume 16, Issue 3 • September 2018

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Lp(a) and Cardiovascular Risk :

Genetic (90%)

Trans fat intake

Hypothyroidism

Renal Insufficiency

Nephrotic Syndrome

FH

FACTORS ASSOCIATED WITH ELEVATED Lp(a)

LipidSpin • Volume 16, Issue 3 • September 2018

1- STATINS : reduces LDL-C which Lp(a) is dependent on , but do not directly lower Lp(a)

2- Niacin: modestly lowers Lp(a)

3- Estrogens

4- PCSK-9 inhibitors ( 20-25%) – but not an indication

5- LDL apheresis may lower Lp(a) by 50-80%

6- Treatment of hypothyroidism and renal disease

TREATMENT

LipidSpin • Volume 16, Issue 1 • February 2018

NEW THERAPIES

1- when checking Lipids ( at least once)

2- assessing risk stratification

3- premature ASCVD

4- Familial Hypercholesterolemia

5- AND WHEN THE STANDARD LIPID PANEL DOES NOT EXPLAIN THE PROBLEM !

WHEN SHOULD YOU MEASURE Lp(a) ?

results1.Releases Official Scientific Statement Regarding Use of Lipoprotein(a) in Clinical PracticeNational Lipid Association 2018

CASE #2

• 46 y/o Eastern European male with an unknown family hx for dyslipidemia presents with this lipid panel :

TC= 210

• LDL-C= 159

• TG= 110

• VLDL= 22

• HDL-C = 33

• BP- 130/78, nonsmoker, meds: HCTZ 25 mg

ASCVD RISK CALCULATOR

• 10 yr Risk : 5.3% (optimal 1.3%)

• Lifetime Risk 50.4% ( optimal 5.2%)

• ? Family Hx

• Coronary Calcium Score: 155

RX= ROSUVASTATIN 10MG

Mg/dl BASELINE 3 MONTHS LATER

TOTAL CHOL 210 239

LDL-C 159 176

HDL-C 33 30

TG 110 163

VLDL-C 22 33

WHY???

CASE #2 CONTINUED…..

ALT= 148 (16-61)

AST= 155 (15-37)

ALK PHOS= 162 ( 45-117)

Total Bili= 2.3 (0.2-1.0)

Images.com

Symptoms

• Abdominal/epigastric pain

• Diarrhea/steatorrhea

• Chest pain

• malabsorption

• Vomiting

• Cholestasis

Signs

• Hepatomegaly/hepatosplenomegaly

• Anemia

• Poor Growth

• CAD

• Stroke

• Aneurysm

• Adrenal calcification

• Esophageal varices

• Elevated TC and LDL

• Decreased HDL

• Elevated LFTs

Reiner Z. et al. Atherosclerosis. 204;235:21-30

• Lysosomal Acid Lipase Activity, Blood - Lysosomal acid lipase deficiency (LAL-D) is a lipid storage disorder with two clinically distinct phenotypes, Wolman disease (WD) and cholesteryl ester storage disease (CESD). Both phenotypes follow an autosomal recessive inheritance pattern and are caused by mutation in the LIPA gene.

• LAL-D is likely underdiagnosed and frequently diagnosed incidentally after liver pathology reveals findings similar to non- alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).

•The LAL-D test is used to evaluate patients with a clinical presentation suggestive of lysosomal acid lipase deficiency and support a diagnosis of disease.

••

Reiner Z. et al. Atherosclerosis. 204;235:21-30

DIAGNOSTIC TESTING

• Measurement of LAL activity: Dried Blood Spot using Lalistat ( LAL inhibitor which measures the difference between the total lipase activity and LAL and if the difference is <3% it is diagnostic)

• Genetic testing : ( expensive and complex)

• Liver biopsy: microvesicular steatosis and hypertrophic Kupffercells and cholesterol ester crystals

Reiner Z. et al. Atherosclerosis. 204;235:21-30

TREATMENT

Sebelipase alfa, sold under the brand name Kanuma, is a recombinant form of the enzyme lysosomal acid lipase (LAL) that is used for the treatment of lysosomal acid lipase deficiency (LAL-D).

It is administered via intraveneous infusion. It was approved for medical use in the European Union and in the United States in 2015.

Drugs.com

When Patients present with lipid abnormalities , they may have lipid profiles similar to Heterozygous FH or Familial Combined Hyperlipidemia

Hepatic manifestations of the disease may be confused with NAFLD or NASH or cryptogenic liver disease

Bernstein DL, et al. J Hepatol. 2013;58:1230-43. doi:10.1016/j.jhep.2013.02.014. 2. Liu J, et al. Am J Cardiol. 2006;98:1363-8. doi:10.1016/j.amjcard.2006.06.032