A 31-year-old man is referred to you for hyperlipidemia assessment. He has no previous cardiovascular history himself and denies any first-degree relatives with a history of CHD although his father and paternal uncle are treated for elevated cholesterol and triglycerides (TGs). He reports that two uncles and a cousin have had heart attacks at young ages. His physical examination reveals a body mass index (BMI) of 32, arcus cornea and xanthelasmas but no xanthomas, and a blood pressure (BP) of 150/80 mmHg. His fasting lipid profile is as follows: total cholesterol (TC) 300 mg/dL, TGs 430 mg/dL, high-density lipoprotein cholesterol (HDL-C) 50 mg/dL, direct LDL-C 202 mg/dL. Fasting blood glucose is 112 mg/dL.
Which primary dyslipidemia is this patient most likely to have?
A. Polygenic hypercholesterolemiaFamilial combined hyperlipidemia. Familial combined hyperlipidemia is a common dyslipidemia (1 in 33 to 1 in 100 individuals) characterized by complex inheritance. Xanthomas are rarely present (unlike in heterozygous FH), but xanthelasmas and arcus cornea can be seen. They are generally overweight, are hypertensive, and have insulin resistance or diabetes. Affected individuals generally exhibit a TC of 250 to 350 mg/dL, LDL-C of 200 to 300 mg/dL, and TG of >140 mg/dL (two-thirds of patients have TG of 200 to 500 mg/dL). Patients with polygenic hypercholesterolemia (1 in 20 to 1 in 100 individuals) have alterations in the function or expression of several key proteins involved in LDL metabolism including defective LDLR and apoB100, and the presence of the apoE4 allele (which has a higher affinity for the LDL-R than the other apoE isoforms leading to downregulation of LDL-R). They have similar elevations in LDL-C as familial combined hyperlipidemia except they do not generally have elevated TG. Hyperapobetalipoproteinemia is associated with increased apoB synthesis. TG may be normal or elevated and arcus cornea and xanthelasmas may be present. However, LDL-C is typical below 160 mg/dL. Familial endogenous hypertriglyceridemia is associated with increased hepatic VLDL formation and TG of 200 to 500 mg/dL but without significant elevations in LDL-C and is not consistently linked with increased CVD risk.