Polygenic Hypercholesterolemia Clinical Presentation

Updated: Apr 09, 2021
  • Author: Catherine Anastasopoulou, MD, PhD, FACE; Chief Editor: George T Griffing, MD  more...
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Hypercholesterolemia is usually discovered during routine screening and does not produce symptoms. Hypercholesterolemia is more common in individuals with a family history of the condition, but lifestyle factors (eg, a diet high in saturated fat) clearly play a major role.

It is important to elicit history about cigarette smoking, diabetes mellitus, and sedentary lifestyle that may contribute to development of hypercholesterolemia and increased cardiovascular risk.



Tendon xanthomas are not present in persons with polygenic hypercholesterolemia. If tendon xanthomas are present, familial hypercholesterolemia or familial defective apoprotein B-100 is the correct diagnosis. Eruptive xanthomas signify extreme hypertriglyceridemia. Xanthelasmas may be present but do not necessarily indicate hypercholesterolemia. Secondary hypercholesterolemia is suggested by stigmata of liver disease, hypothyroidism, hypopituitarism, nephrotic syndrome, and chronic renal disease.



Several drugs and disease states are associated with hypercholesterolemia; however, for the overwhelming majority of patients, the Western lifestyle of a high-fat diet superimposed on a susceptible genotype appears to cause hypercholesterolemia. Nonetheless, ensuring that the patient does not have untreated hypothyroidism, renal disease, or liver disease is important. Furthermore, progestins, anabolic steroids, and glucocorticoids may adversely affect low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) values.

The risk factors for coronary heart disease (CHD), other than LDL-C, in the US National Cholesterol Education Program (NCEP) screening and treatment algorithm are as follows:

  • Age and sex - Men aged 45 years or older; women aged 55 years or older

  • Family history of premature CHD (male first-degree relative < 55 y, female first-degree relative < 65 y)

  • Current cigarette smoking

  • Hypertension - Blood pressure greater than or equal to 140/90 mm Hg or current antihypertensive drug therapy

  • Low HDL-C concentration - Less than 40 mg/dL, but one risk factor subtracted if HDL-C concentration is more than 60 mg/dL (This level has been increased from < 35 mg/dL compared with the value from the NCEP Adult Treatment Panel II [NCEP ATP II].)