Monitor serum concentrations of triglyceride or cholesterol for hyperlipidemia - DVM
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Monitor serum concentrations of triglyceride or cholesterol for hyperlipidemia


DVM360 MAGAZINE

Q I have been seeing a 14-year-old dog that although seemingly healthy has had repeated serum triglyceride concentrations of 1200 mg/dl. Should I be concerned? What should I do?

 

 A This laboratory result represents what is technically classified as hyperlipidemia and, specifically, hypertriglyceridemia. The following review will provide some current information about canine hyperlipidemia (and hypertriglyceridemia) and possibly answers to your questions.

Hyperlipidemia is defined as an increase in serum concentrations of triglyceride or cholesterol or both.

Hyperlipidemia causes

Canine hyperlipidemias may occur from an inherited defect of lipoprotein metabolism (and is termed as primary or familial hyperlipidemia). Canine hyperlipidemias may also occur as a result of systemic disease (and is referred to as secondary hyperlipidemia). Canine hyperlipidemias in which neither hereditary nor underlying metabolic disease can be documented are termed idiopathic hyperlipidemia.

The most common cause of canine hyperlipidemias is postprandial hyperlipidemia - a physiologic event resulting from the appearance of chylomicrons in the circulation between two and six hours after fat ingestion.

Triglyceride concentrations

The triglyceride concentration at this time may be sufficient to impart an opaque or milky appearance to the serum because of the refractive properties of the triglyceride-rich lipoproteins. Clearance of chylomicrons from the circulation allows a return to fasting triglyceride concentrations between eight and 16 hours after a meal. Lipemia is not recognized in association with hypercholesterolemia. Serum cholesterol concentrations show a small postprandial rise that does not usually exceed the upper limit of the expected reference range.

Associated disease

A fasting hypertriglyceridemia may result from impaired clearance of chylomicrons and very low-density lipoproteins from the circulation or from overproduction of very low-density lipoproteins. Canine hypertriglyceridemia is most commonly associated with diabetes mellitus, hypothyroidism, hyperadrenocorticism and protein-losing nephropathy. Obesity has not been associated with overt fasting hyperlipidemia, but it appears that a relationship between adiposity and impaired serum triglyceride clearance does exist. This may result in a more severe or prolonged postprandial hyperlipidemia and may predispose obese dogs to the clinical consequences of hypertriglyceridemia.

There also exists an association between acute pancreatitis and canine hypertriglyceridemia. The familial hypertriglyceridemia is uncommon and most likely seen in the middle-aged and older Miniature Schnauzer and Beagle. This familial hypertriglyceridemia is characterized by increase in serum triglyceride concentration secondary to an excessive accumulation of chylomicrons and very low-density lipoproteins. A moderate increase in serum cholesterol concentration may also be noted.

Hypercholesterolemia

Canine hypercholesterolemia is most commonly associated with hypothyroidism, diabetes mellitus, hyperadrenocorticism, protein-losing nephropathies and obstructive biliary tract disease. It is possible to induce hypercholesterolemia in the dog by dietary manipulation, but the current existing fat content of commercial dog foods is hard to achieve hypercholesterolemia in dogs with normal lipid metabolism. Primary canine hypercholesterolemia has not been diagnosed, but increased serum concentrations of high-density lipoproteins have been reported in a family of Briards in the United Kingdom.

Hypertriglyceridemia: clinical problems

Canine hypertriglyceridemia, where fasting triglyceride concentration is >500 mg/dl, is associated with a number of clinical problems. The severity of the clinical signs may not correlate with the degree of hypertriglyceridemia. Hypertriglyceridemia is most commonly associated with gastrointestinal signs, including intermittent episodes of non-localizing abdominal pain, anorexia and vomiting. In some individuals, the laboratory results may be supportive of a tentative diagnosis of acute pancreatitis. However, the serum amylase and lipase activities and the appearance of abdominal radiographs are considered within normal limits. Gastrointestinal signs may be recognized in any hypertriglyceridemic dog but are most frequently seen in Miniature Schnauzers and Beagles older than 4 years. As affected dogs age, the severity and frequency of the episodes of abdominal pain may increase. However, the gastrointestinal disease may be self-limiting, since anorexia results in a prolonged fast and clearance of the triglyceride-rich lipoproteins from the circulation.

Primary and secondary canine hyperlipidemia may produce ocular signs. The milky appearance of the retinal vessels in non-tapetal areas may be detected on funduscopic examination. This is referred to as lipemia retinalis and is most likely seen in dogs with serum triglyceride concentration greater than 2500 mg/dl or a concentration lower than this in anemic dogs. The lactescence of the retinal vessels does not impair visual function but should alert the veterinarian to the presence of hypertriglyceridemia. Lipid-latent aqueous humor also may occur in hypertriglyceridemic dogs. Other clinical signs associated with hypertriglyceridemia are generalized seizures and xanthomas.

Hypercholesterolemia: clinical signs

Canine hypercholesterolemia is associated with few clinical signs. Ocular abnormalities include arcus lipoides corneae, which is an annular lipid infiltration of the cornea and perilimbal zone of the sclera. This condition has been diagnosed in German Shepherd dogs with concurrent hypothyroidism and hyperlipidemia. Atherosclerosis is a relative uncommon problem in dogs and is usually associated with hypothyroidism. The clinical presentation of affected dogs depends on the location of the diseased vessels but may include iliac thrombosis, behavioral signs and generalized seizures.

Treatment

The serum lipid concentration in secondary canine hyperlipidemia generally return to normal, or near normal, after successful stabilization or treatment of the underlying endocrine or metabolic disease. The serum lipid concentration may decline rapidly as is the case with canine hypothyroidism or remain abnormal for a more prolonged period as frequently seen in dogs with diabetes mellitus. If specific treatment for any underlying endocrine or metabolic disease does not cause resolution of the hyperlipidemia, then additional lipid-lowering strategies should be considered. Dogs with fasting serum triglyceride concentration greater than 500 mg/dl are considered at risk for development of pancreatitis and immediate lipid-lowering management should be instituted. Hypertriglyceridemic dogs presenting with signs typical of pancreatitis should be treated symptomatically for pancreatitis.

Dietary management

Dogs with serum triglyceride concentration greater than 500 mg/dl on consecutive samples taken at two-week to four-week intervals are definitive candidates for dietary management, irrespective of the presence or absences of clinical signs at the time of examination. The primary approach to the dietary management of hypertriglyceridemia is the reduction of fat intake.

A number of commercial low-fat high-fiber diets are available in canned and dry preparations. The diets should be fed according to the manufacturer's guidelines for maintenance except in those cases of obese dogs, where a weight reduction program should be instituted.

The selected diet must be the only food source for the affected dog and the serum lipid concentrations monitored in six to eight weeks after the introduced diet. In many dogs with idiopathic hyperlipidemia, it may be difficult to maintain serum lipid concentrations within laboratory expected reference ranges; therefore, the goal of dietary therapy is to maintain a serum triglyceride concentration of less than 500 mg/dl.

If after six to eight weeks of dietary management, the serum triglyceride concentration has not decreased significantly, it is important to exclude failure of owner compliance as the cause of the ineffective response particularly since low-fat high-fiber diets have poor palatability. A diet with moderately restricted fat content is often sufficient to control the hypertriglyceridemia, but as affected dogs grow older, the episodes of gastrointestinal signs increase in severity or frequency and may require more drastic dietary fat restrictions.

Beyond nutrition

Human lipid-lowering drugs may prove beneficial when dietary management has not completely succeeded. Gemfibrozil is a lipid-lowering drug that is well-tolerated in dogs with hypertriglyceridemia. Gemfibrozil is administered orally at 10 mg/kg BID. Gemfibrizol therapy has produced variable reductions in serum triglyceride concentrations, but it may be a useful adjunct to dietary therapy in cases in which alternative methods have failed to control serum triglyceride concentrations.

Although no side effects have been noted in dogs treated with gemfibrozil, it is advisable to monitor hematologic and serum chemistry parameters every six to eight weeks.

The administration of gemfibrozil should be discontinued if no response has been noted within three months of initiation of the therapy.

Underlying endocrine or metabolic disease

Hypercholesterolemia in the dog is currently considered a useful indicator of underlying endocrine or metabolic disease, rather than an immediate health risk. However, prolong marked increases in the serum cholesterol concentration (> 750 mg/dl) may be associated with the development of atherosclerosis. It is, therefore, important to consider dietary fat restriction in cases of idiopathic hypercholesterolemia. Cholestyramine, a bile acid binding resin (administered at 1 to 2 grams orally every 12 hours), may be used in cases of persistent idiopathic hypercholesterolemia, but its use may also increase hepatic very low-density lipoprotein synthesis; therefore, the serum triglyceride concentrations should be monitored closely.

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