Diagnosis: MI, the irreversible necrosis (death) of heart muscle secondary to ischemia (decreased blood supply), is caused by the occlusion (blockage) of a blood vessel most commonly by a blood clot (thrombus). BJ subsequently is determined to have heterozygous familial hypercholesterolemia (FH), also known as type IIa hyperlipidemia.
Immediate Treatment: BJ is given O2, a vasodilator, pain medication, and drugs to dissolve blood clots (thrombolytics) and reduce clotting (antithrombotics).
Long-Term Treatment: Lipid-lowering drugs (for example, high-potency statins, bile acid [BA] sequestrants, and niacin); daily aspirin; β-blockers; and counseling on nutrition, exercise, and smoking cessation would be part of the long-term treatment plan.
Prognosis: Patients with heterozygous FH have ~50% of the normal number of functional LDL receptors and a hypercholesterolemia (two to three times normal) that puts them at high risk (>50% risk) for premature coronary heart disease (CHD). However, <5% of patients with hypercholesterolemia have FH.
Nutrition Nugget: Dietary recommendations for individuals with heterozygous FH include limiting saturated fats to <7% of total calories and cholesterol to <200 mg/day, substituting unsaturated fats for saturated fats, and adding soluble fiber (10–20 g/day) and plant sterols (2 g/day) for their hypocholesterolemic effects. Fiber increases BA excretion. This results in increased hepatic uptake of cholesterol-rich LDL to supply the substrate for BA synthesis. Plant sterols decrease cholesterol absorption in the intestine.
Genetics Gem: FH is caused by hundreds of different mutations in the gene for the LDL receptor (on chromosome 19) that affect receptor amount and/or function. FH is an autosomal-dominant disease in which homozygotes are more seriously affected than heterozygotes. Heterozygous FH has an incidence of ~1:500 in the general population. It is associated with increased risk of cardiovascular disease. Genetic screening of the first-degree relatives of BJ would identify affected individuals for treatment.
Review Questions: Choose the ONE best answer.
RQ1. Triacylglycerols are glycerol-based lipids. Which of the following is also a glycerol-based lipid? A. Ganglioside GM2
B. Phosphatidylcholine C. Prostaglandin PGI2
D. Sphingomyelin
E. Vitamin D RQ2. Statins are of benefit to patients with hypercholesterolemia because they:
A. decrease a rate-limiting and regulated step of de novo cholesterol biosynthesis by inhibiting hydroxymethylglutaryl coenzyme A (HMG CoA) reductase.
B. decrease expression of the gene for the LDL receptor by preventing the movement of the sterol regulatory element–binding protein-2 (SREBP 2) in complex with SREBP cleavage–activating protein (SCAP) from the membrane of the endoplasmic reticulum to the membrane of the Golgi.
C. increase the oxidation of cholesterol to CO2 + H2O.
D. interfere with the absorption of bile salts in the enterohepatic circulation, thereby causing the liver to take up cholesterol from the blood for use in BA synthesis.
E. reduce cholesterol by increasing steroid hormone and vitamin D synthesis.
RQ3. Statins are competitive inhibitors of HMG CoA reductase. Which of the following statements about competitive inhibitors is correct?
A. Competitive inhibitors are examples of irreversible inhibitors.