Secondary causes of hyperlipidemia

Secondary causes of hyperlipidemia are important to recognize. In fact, hyperlipidemia may be a clue to the presence of an underlying systemic disorder. It may greatly heighten the risk of atherosclerosis with a raised LDL-c, triglyceride-rich lipoprotein excess, and increased lipoprotein(a) as well as lowered HDL-c. The search for secondary causes may provide a clue as to why patients with primary lipid disorders suddenly develop worsening lipid profiles. The point is a crucial one because some acquired causes of hyperlipidemia, such as alcohol, estrogens, steroids, or pregnancy, when superimposed on a primary familial form of hypertriglyceridemia can result in a saturated removal system and a buildup of chylomicrons, which can lead to life-threatening pancreatitis. A convenient way to remember secondary causes is to think of the four D's of diet, drugs, disorders of metabolism, and diseases. Although diets rich in saturated fats and cholesterol are a common cause of the mild hypercholesterolemia seen in our society, alcohol excess and weight gain can explain much of the tendency toward hypertriglyceridemia. Interestingly anorexia nervosa has long been associated with severe but reversible bypercholesterolemia. Several classes of drugs need to be considered as common causes of altered lipid profiles. Glucocorticoids and estrogens elevate triglycerides and raise levels of HDL-c. Anabolic steroids taken orally markedly reduce levels of HDL-c in contrast to injectable testosterone, which does not adversely affect the LDL-to-HDL ratio. Oral contraceptives affect atherosclerotic risk depending on the kind and doses of progestin/estrogen. In those with an underlying primary hypertriglyceridemia and associated obesity, estrogenic medications can depress triglyceride removal mechanisms, leading to the chylomicronemia syndrome and pancreatitis. Antihypertensives have variable effects on lipids and lipoproteins. Although short-term thiazide usage raises cholesterol, triglycerides, and LDL-c, long- term usage is not necessarily associated with significant alterations in lipid levels. Alpha blockers may cause an increase in HDL-c, whereas beta blockers raise triglycerides and lower HDL-c. Symphatholytics, angiotensin converting enzyme inhibitors, and calcium channel blockers are essentially lipid neutral. Retinoids can be associated with increased LDL-to-HDL ratios and occasionally striking elevations in triglycerides. Cyclosporine raises LDL-c and lipoprotein(a). Classes of drugs that may raise HDL-c include cimetidine, antiepileptic drugs, and tamoxifen, but the effect may be seen primarily in women. Hypothyroidism is the most common secondary cause of hyperlipidemia after dietary causes are considered. A thyroxine and TSH level should be obtained on all new cases of clinically important hyperlipidemia. Obesity, diabetes mellitus, and pregnancy are important hormonal disorders that have a primary effect on triglyceride and HDL metabolism. When superimposed on a familial triglyceride disorder, the chylomicronemia syndrome as described earlier can result. Systemic disorders, such as liver, kidney, and immunology disorders, can be secondary causes of hyperlipidemia. Liver disease when characterized by cholestasis can cause severe hypercholesterolemia owing to an abnormal lipoprotein, Lp-X, which lacks apo B and is not governed by the LDL receptor. Plasma exchange may be required to control its manifestations. Patients with renal failure may have heightened atherosclerosis owing to accumulation of triglyceride-rich lipoproteins as a result of impaired triglyceride clearance. Those with nephrosis have heightened LDL production rates in part driven by urinary losses of albumin and lower HDL-c owing to loss of HDL in the urine. Transplantation improves underlying organ function and lipid abnormalities owing to this, but owing to weight gain, prednisone, and immunosuppresive therapy (e.g., cyclosporine), can be associated with a complex form of secondary hyperlipidemia. Thus, in general, treatment of the underlying disorder or alteration or discontinuation of drug therapy can lead to improvement. Specific lipid- lowering therapy may still be required to reduce the risk of atherosclerosis or pancreatitis after the aforementioned steps are accomplished. Drug dosages may need to be modified in the setting of organ dysfunction or multiple medications.