Monitor serum concentrations of triglyceride or cholesterol for hyperlipidemia

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

 A This laboratory result represents what is technicallyclassified as hyperlipidemia and, specifically, hypertriglyceridemia. Thefollowing 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 triglycerideor cholesterol or both.

Hyperlipidemia causes

Canine hyperlipidemias may occur from an inherited defect of lipoproteinmetabolism (and is termed as primary or familial hyperlipidemia). Caninehyperlipidemias may also occur as a result of systemic disease (and is referredto as secondary hyperlipidemia). Canine hyperlipidemias in which neitherhereditary nor underlying metabolic disease can be documented are termedidiopathic hyperlipidemia.

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

Triglyceride concentrations

The triglyceride concentration at this time may be sufficient to impartan opaque or milky appearance to the serum because of the refractive propertiesof the triglyceride-rich lipoproteins. Clearance of chylomicrons from thecirculation allows a return to fasting triglyceride concentrations betweeneight and 16 hours after a meal. Lipemia is not recognized in associationwith hypercholesterolemia. Serum cholesterol concentrations show a smallpostprandial rise that does not usually exceed the upper limit of the expectedreference range.

Associated disease

A fasting hypertriglyceridemia may result from impaired clearance ofchylomicrons and very low-density lipoproteins from the circulation or fromoverproduction of very low-density lipoproteins. Canine hypertriglyceridemiais most commonly associated with diabetes mellitus, hypothyroidism, hyperadrenocorticismand protein-losing nephropathy. Obesity has not been associated with overtfasting hyperlipidemia, but it appears that a relationship between adiposityand impaired serum triglyceride clearance does exist. This may result ina more severe or prolonged postprandial hyperlipidemia and may predisposeobese dogs to the clinical consequences of hypertriglyceridemia.

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

Hypercholesterolemia

Canine hypercholesterolemia is most commonly associated with hypothyroidism,diabetes mellitus, hyperadrenocorticism, protein-losing nephropathies andobstructive biliary tract disease. It is possible to induce hypercholesterolemiain the dog by dietary manipulation, but the current existing fat contentof commercial dog foods is hard to achieve hypercholesterolemia in dogswith normal lipid metabolism. Primary canine hypercholesterolemia has notbeen diagnosed, but increased serum concentrations of high-density lipoproteinshave been reported in a family of Briards in the United Kingdom.

Hypertriglyceridemia: clinical problems

Canine hypertriglyceridemia, where fasting triglyceride concentrationis >500 mg/dl, is associated with a number of clinical problems. Theseverity 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, anorexiaand vomiting. In some individuals, the laboratory results may be supportiveof a tentative diagnosis of acute pancreatitis. However, the serum amylaseand lipase activities and the appearance of abdominal radiographs are consideredwithin normal limits. Gastrointestinal signs may be recognized in any hypertriglyceridemicdog but are most frequently seen in Miniature Schnauzers and Beagles olderthan 4 years. As affected dogs age, the severity and frequency of the episodesof abdominal pain may increase. However, the gastrointestinal disease maybe self-limiting, since anorexia results in a prolonged fast and clearanceof 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 bedetected on funduscopic examination. This is referred to as lipemia retinalisand is most likely seen in dogs with serum triglyceride concentration greaterthan 2500 mg/dl or a concentration lower than this in anemic dogs. The lactescenceof the retinal vessels does not impair visual function but should alertthe veterinarian to the presence of hypertriglyceridemia. Lipid-latent aqueoushumor also may occur in hypertriglyceridemic dogs. Other clinical signsassociated with hypertriglyceridemia are generalized seizures and xanthomas.

Hypercholesterolemia: clinical signs

Canine hypercholesterolemia is associated with few clinical signs. Ocularabnormalities include arcus lipoides corneae, which is an annular lipidinfiltration of the cornea and perilimbal zone of the sclera. This conditionhas been diagnosed in German Shepherd dogs with concurrent hypothyroidismand hyperlipidemia. Atherosclerosis is a relative uncommon problem in dogsand is usually associated with hypothyroidism. The clinical presentationof affected dogs depends on the location of the diseased vessels but mayinclude iliac thrombosis, behavioral signs and generalized seizures.

Treatment

The serum lipid concentration in secondary canine hyperlipidemia generallyreturn to normal, or near normal, after successful stabilization or treatmentof the underlying endocrine or metabolic disease. The serum lipid concentrationmay decline rapidly as is the case with canine hypothyroidism or remainabnormal for a more prolonged period as frequently seen in dogs with diabetesmellitus. If specific treatment for any underlying endocrine or metabolicdisease does not cause resolution of the hyperlipidemia, then additionallipid-lowering strategies should be considered. Dogs with fasting serumtriglyceride concentration greater than 500 mg/dl are considered at riskfor development of pancreatitis and immediate lipid-lowering managementshould be instituted. Hypertriglyceridemic dogs presenting with signs typicalof pancreatitis should be treated symptomatically for pancreatitis.

Dietary management

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

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

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

If after six to eight weeks of dietary management, the serum triglycerideconcentration has not decreased significantly, it is important to excludefailure of owner compliance as the cause of the ineffective response particularlysince low-fat high-fiber diets have poor palatability. A diet with moderatelyrestricted fat content is often sufficient to control the hypertriglyceridemia,but as affected dogs grow older, the episodes of gastrointestinal signsincrease in severity or frequency and may require more drastic dietary fatrestrictions.

Beyond nutrition

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

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

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

Underlying endocrine or metabolic disease

Hypercholesterolemia in the dog is currently considered a useful indicatorof underlying endocrine or metabolic disease, rather than an immediate healthrisk. 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 casesof idiopathic hypercholesterolemia. Cholestyramine, a bile acid bindingresin (administered at 1 to 2 grams orally every 12 hours), may be usedin cases of persistent idiopathic hypercholesterolemia, but its use mayalso increase hepatic very low-density lipoprotein synthesis; therefore,the serum triglyceride concentrations should be monitored closely.