Treatment of Hyperlipidemia

6. Treatment of Hyperlipidemia

Because of the clinical signs associated with primary hyperlipidemia, and the potential risks, hyperlipidemia should be treated aggressively in the cat. The underlying disorder in a secondary hyperlipidemia should be treated, but there is no specific therapeutic regimen for cats with inherited hyperchylomicronemia.

Fat Restricted-diet

The main therapy of primary hyperlipidemia involves feeding a low-fat diet with moderate protein content. Diets low in protein may cause an increase in serum cholesterol concentration (Hansen et al, 1992), and are therefore not recommended unless the presence of other conditions warrant their use. Human patients with inherited hyperchylomicronemia typically must restrict dietary fat intake to less than 15% of calories to control hyperlipidemia.

Feline diets with less than 10% fat (as-fed) or less than 30 g fat/1000 kcal are generally adequate. Protein content should be maintained at about 30% as-fed, or greater than 85 g protein/1000 kcal. A diet should not be chosen only on the percent fat present in the diet; the diet should be low in fat based on metabolizable energy (ME). Some diets appear low in fat on a percentage basis, but actually provide a higher fat content than expected when the amount of fiber in the diet and metabolizable energy are taken into account. For example, a diet containing 11% fat with an ME of 4000 kcal/kg provides only 27.5 g fat/1000 kcal, whereas a diet containing 9% fat with an ME of 3000 kcal/kg provides 30 g fat/1000 kcal (Table 5). The presence of a blend of fructooligosaccharides and beet pulp in the diet may also be desirable, since this blend has been shown to decrease serum triglyceride and cholesterol concentrations in the dog (Diez et al, 1997).

Obesity in association with familial hyperchylomicronemia is uncommon, so it is usually not necessary to restrict caloric intake. If the cat is not obese, the amount of food offered may need to be increased because of the decreased calories provided by the new diet with decreased fat content. Many cats can continue to be fed free-choice. Treats should be restricted since these are most likely not low in fat content.

After feeding a low-fat diet for approximately 4 weeks, the presence of hyperlipidemia should be re-evaluated. Most cats will show at least partial resolution of hyperlipidemia with consumption of low-fat diets. Body condition should be assessed, and if there has been significant weight loss, the patient should receive an increased amount of diet, or possibly be switched to a different diet with higher caloric density.

If after 4 weeks hyperlipidemia is still present, the diet should be continued, and all other sources of food or treats removed. If there has been good owner compliance, then a switch to a different low-fat diet could be considered. The patient should then be reassessed after another one to two months. If hyperlipidemia still persists at that time, drug therapy could be added.

Omega-3 fatty Acid Supplementation

Fish oils are rich in omega-3 fatty acids, and have been the supplement of choice in the treatment of dogs with primary hyperlipidemias. However, little is known about the effectiveness of fish oil therapy in cats. Potential doses range from 10 to 200 mg/kg body weight. The fish oil supplement should contain a high percentage of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as these are long-chain omega-3 fatty acids. Products containing a high level of linolenic acid (also an omega- 3 fatty acid) will not be as effective, as cats have very low delta-6 desaturase necessary for the conversion of linolenic acid to longer chain omega-3 fatty acids (Sinclair et al, 1979) (Figure 11).

Figure 11. Metabolism of linolenic acid (omega-3).

The use of fish oil in the treatment of hyperlipidemia has been extensively studied in a number of other species. Fish oil supplement has resulted in a decrease in serum triglyceride and cholesterol in humans (Okumura et al, 2002), rats (Adan et al, 1999), chicks (Castillo et al, 2000), dogs (Brown et al, 2000), and rabbits (Mortensen et al, 1998).

Omega-3 fatty acids act to decrease the synthesis of triglyceride and VLDL in the liver (Harris et al, 1990; Connor et al, 1993), stimulate LPL activity (Levy et al, 1993), decrease the intestinal absorption of lipid (Thomson et al, 1993), and increase cholesterol secretion into bile (Smit et al, 1991). Fish oil also decreases the serum concentration of free fatty acids (Singer et al, 1990), which may be important in the prevention of pancreatitis and diabetes mellitus.

Unfortunately there are no long-term studies to verify the safety and efficacy of any lipid-lowering agent in cats, and any therapy should be used with caution. One concern with fish oil therapy is the evidence that fish oil increases the concentration of lipoperoxides in LDL (Puiggros et al, 2002). The addition of vitamin E to the fish oil therapy regimen may enhance beneficial effects by increasing glutathione reductase activity and decreasing peroxide levels (Hsu et al, 2001).

Other Therapeutic Agents

Other therapeutic agents have been used with variable results.

• Gemfibrozil has been used to stimulate LPL activity and decrease VLDL secretion (Santamarina-Fojo & Dugi, 1994), and in cats is used at a dosage of 7.5 to 10 mg/kg body weight twice daily.
• Niacin therapy has been used, however adverse effects have been noted (Bauer, 1995).
• Garlic extracts have been used to decrease cholesterol in humans (Steiner et al, 1996), but have not been evaluated in cats.
• HMGCoA reductase inhibitors reduce cholesterol synthesis and increase the excretion of LDL from the circulation, but their effectiveness in cats has not been studied.
• Thyroxine therapy can decrease serum total cholesterol in humans (Brun et al, 1980), and is effective in lowering lipid concentrations in hypothyroid dogs, but its use has not been recommended for cats.

The mutation characterizing the LPL deficiency present in humans and cats with hyperchylomicronemia has been identified, and gene transfer therapy has been attempted. Lipoprotein lipasedeficient cats were given an injection of an adenoviral vector containing the human LPL gene, with disappearance of triglyceride-rich lipoproteins up to day 14, at which time antibodies against the human LPL protein were detected (Liu et al, 2000). Concurrent administration of immunosuppressive therapy delayed antibody production, with resolution of hyperlipidemia for three weeks after administration (Ross et al, 2006). Gene replacement therapy for inherited hyperchylomicronemia may become a reality in the future.

Conclusion

There are a number of conditions that can cause hyperlipidemia in the feline. Postprandial hyperlipidemia should always be verified, and secondary causes of hyperlipidemia must be ruled out. A number of the causes of secondary hyperlipidemia are uncommon in the cat (hypothyroidism, hyperadrenocorticism), or are fairly evident based on clinical signs or biochemical profile (diabetes mellitus, pancreatitis). If an underlying cause of hyperlipidemia is present, treatment of the primary disease is usually effective at resolving the secondary hyperlipidemia. Primary causes of hyperlipidemia should be aggressively treated because of the potential complications and clinical signs associated with persistent hyperlipidemia.