Hyperlipidemias familial combined

BARs are useful in treating primary hypercholesterolemia (familial hypercholesterolemia, familial combined hyperlipidemia, type Ila hyperlipoproteinemia). 

Familial combined hyperlipidemia may respond better to a fibrate and a statin than to a fibrate and a BAR. 

F13. Fonda, M., DaCol, P. G., La Verde, R., Battello, C., Fisicaro, M., Tonizzo, M., and Cattin, L., Lipoprotein(a) serum concentration in familial combined hyperlipidemia. Clin. Chim. Acta 223, 121-127(1993). 

Familial combined hyperlipidemia lib LDL, VLDL Chol,TG Increased VLDL production, increased conversion of VLDL to LDL. CHD, stroke... 

Dietary measures are initiated first—unless the patient has evident coronary or peripheral vascular disease—and may obviate the need for drugs. Patients with familial hypercholesterolemia or familial combined hyperlipidemia always require drug therapy. Cholesterol and saturated and trans-fats are the principal factors that increase LDL, whereas total fat, alcohol, and excess calories increase triglycerides. 

Reductase inhibitors are useful alone or with resins, niacin, or ezetimibe in reducing levels of LDL. Women with hyperlipidemia who are pregnant, lactating, or likely to become pregnant should not be given these agents. Use in children is restricted to selected patients with familial hypercholesterolemia or familial combined hyperlipidemia. 

This combination is sometimes useful in treating patients with familial combined hyperlipidemia who are intolerant of niacin or statins. However, it may increase the risk of cholelithiasis. 

Mixed hyperlipidemia is one of the most common lipid disorders, but only a minor fraction of the affected patients has a monogenic inherited disease. Most patients with mixed hyperlipidemia have a familial combined hyperlipidemia, a multifactorial disease for which the causative factors are not known. Patients have elevated remnant lipoproteins with elevated triglycerides > 3.0 mmol/1 and total cholesterol > 5.0 mmol/1. Two rare monogenic disorders lead to such a lipoprotein pattern,... 

Athyros VG, Papageorgiou AA, Hatzikonstandinou HA, Didangelos TP, Carina MV, Kranitsas DF, Kontopoulos AG. Safety and efficacy of long-term statin-fibrate combinations in patients with refractory familial combined hyperlipidemia. Am J Cardiol 1997 80(5) 608-13. 

Groenendijk M, De Bruin TW, Dallinga-Thie GM. Two polymorphisms in the apo A-IV gene and familial combined hyperlipidemia. Atherosclerosis. 2001, 158 369-76. 

Hausmann D, Johnson JA, Sudhir K, et al. Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia correlation with high density lipoproteins, J Am Coll Cardiol I 996 27 1 562-1 570. 

Familial Combined Hyperlipidemia About 10% to 15% of patients with premature CHD actually have familial combined hyperlipidemia (FCHL). This disorder is recognized as a distinct phenotype by studying family members of survivors of myocardial infarction. Patients with FCHL can have increased plasma concentrations of total and LDL cholesterol (type Ila), or triglyceride (type IV), or both (type lib). In all cases, apo B-lOO concentrations are increased. The presentation of lipoprotein patterns can vary in an individual with time. Furthermore, patients with hypertriglyceridemia with normal partners tend to have offspring with hypercholesterolemia, and vice versa. 

Llaverias G, Pou J, Ros E, Zambon D, Cofan M, Sanchez A, Vazquez-Carrera M, Sanchez RM, Laguna JC, Alegret M (2008) Monocyte gene-expression profile in men with familial combined hyperlipidemia and its modification by atorvastatin treatment. Pharmacogenomics 9 1035-1054... 

S. Reynisdottir, B. Angelin, and D. Langin, et al.. Adipose tissue lipoprotein lipase and hormone-sensitive lipase. Contrasting findings in familial combined hyperlipidemia and insulin resistance syndrome, Arterioscler. Thromh. Vase. 

Familial combined hyperlipidemia is characterized by elevations in total cholesterol and triglycerides, decreased HDL, increased apolipoprotein B, and small, dense LDL. It is associated with premature CHD and may be difficult to diagnose because the lipid levels do not consistently display the same pattern. 

Type TV hyperlipoproteinemia is common and occurs in adulthood primarily in patients who are obese, diabetic, and hyperuricemic and do not have xanthomas. It may be secondary to alcohol ingestion and can be aggravated by stress, progestins, oral contraceptives, thiazides, or 8-blockers. Two genetic patterns occur in type IV hyperlipoproteinemia familial hypertriglyceridemia, which does not carry a great risk for premature CAD, and familial combined hyperlipidemia, which is associated with increased risk of cardiovascular disease. 

Veerkamp Ml, de Graaf J, Hendriks JCM, et al. Nomogram to diagnose familial combined hyperlipidemia on the basis of results of a 5-year follow-up study. Circulation 2004 109 2980-2985. 

The fact that a number of different abnormal lipoprotein profiles were found in Cora Nari and her siblings, and that each had evidence of coronary artery disease, suggests that Cora has familial combined hyperlipidemia (FCH). This diagnostic impression is further supported by the finding that Cora s profile of lipid abnormalities appeared to change somewhat from one determination to the next, a characteristic of FCH. This hereditary disorder of lipid metabolism is believed to be quite common, with an estimated prevalence of about 1 per 100 population. 

Because Cora Nari s lipid profile indicated an elevation in both serum j triacylglycerols and LDL cholesterol, she was classified as having a com-bined hyperlipidemia. The dissimilarities in the lipid profiles of Cora and her two siblings, both of whom were experiencing anginal chest pain, is characteristic of the multigenic syndrome referred to as familial combined hyperlipidemia (FCH). 

The resins cause a modest reduction in LDL cholesterol (Table 35-3) but have little effect upon HDL cholesterol or triglycerides. In some patients with familial combined hyperlipidemia, resins can increase VLDL. 

Items 3-6 A 35-year-old woman apperu to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL cholesterol, and triglyceride are elevated. Her serum concentration of HDL cholesterol is somewhat reduced. 

In some patients with familial combined hyperlipidemia and elevated VLDL, the resins can increase VLDL and triglyceride concentrations even though they also lower LDL cholesterol. The answer is (B). 

All HMGRIs are approved for the treatment of primary hypercholesterolemia and familial combined hyperlipidemia (Fredrickson s type Ha and lib) (Table 30.2) In patients who have not responded to diet, exercise, and other non pharmacological methods (Table 30.6) (15,21). They may be used either alone or In combination with bile acid sequestrants, ezetimibe, or niacin. As previously mentioned, they should be administered at least 1 hour before or 4 to 6 hours after bile acid sequestrants when this combination Is desired. Fluvastatin, lovastatin, pravastatin, and simvastatin have been specifically Indicated to reduce the mortality of CHD and stroke. By reducing plasma LDL levels, these compounds slow the progression of atherosclerosis and reduce the risk of myocardial Infarction and other ramifications of vascular occlusion. Atorvastatin, rosuvastatin, and simvastatin have been shown to be effective In homozygous familial hyperlipidemia and are Indicated for this use. Additionally, atorvastatin, pravastatin, and simvastatin are Indicated for primary dysbetallpoprotelnemla (Fredrickson s type III) (Table 30.2). Finally, atorvastatin, pravastatin, rosuvastatin, and simvastatin are Indicated for the treatment of hypertriglyceridemia. 

Fibrates are approved to treat hypertriglyceridemia and familial combined hyperlipidemia (Fredrickson s type lla, lib, IV, and V) (Table 30.2) in patients who are at risk of pancreatitis and have not responded to dietary adjustments or in patients who are at risk of CHD and have not responded to weight loss, dietary adjustments, and other pharmacological treatment. They can be used either alone or in combination with niacin, bile acid sequestrants, or FlMGRIs. If used with bile acid sequestrants, fibrates must be taken either 1 hour before or 4 to 6 hours after the sequestrant. As discussed previously and reemphasized below, caution should be used it fibrates are combined with HMGRIs. Fibrates are not effective in the treatment of hypertriglyceridemia associated solely to elevated chylomicron levels (Fredrickson s type I). 

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