Hyperlipidemia
Background
Hyperlipidemia is caused by increased plasma triglycerides, cholesterol, or both and is a normal postprandial finding; within 0.5 to 2 hours of consuming dietary fat, chylomicrons appear and remain in the blood for 6 to 10 hours. In a fasted (>12 hours) sample, hyperlipidemia is caused by a disturbance in the metabolism of the lipoprotein responsible for carrying hydrophobic fat to and from tissue (eg, intestine, muscle, adipose, liver).1 Therefore, hyperlipoproteinemia has been used interchangeably with hyperlipidemia when an abnormally high plasma lipoprotein is identified.
Increased fasted lipoprotein blood levels are associated with either an overproduction or decreased removal of the specific lipoprotein and the type of fat it carries. High blood concentrations of chylomicrons and very-low-density lipoprotein (VLDL) will appear as high plasma triglyceride levels, whereas high concentrations of high-density lipo-protein (HDL) and/or low-density lipoprotein (LDL) raise plasma cholesterol levels. Hypertriglyceridemia is more clinically relevant than hypercholesterolemia.
Primary lipoprotein metabolism disorders are relatively uncommon and associated with specific breeds (eg, miniature schnauzer, Shetland sheepdog, briard, rough collie, Doberman, rottweiler).2 Secondary hypertriglyceridemia is clinically more common and caused by several primary disorders. Endocrine disease (eg, diabetes mellitus [DM], hypothyroidism, hyperadrenocorticism), pancreatitis, obesity, protein-losing nephropathy (PLN), and cholestasis are known to cause or be associated with secondary hypertriglyceridemia.2
Clinical Signs
Common, mild presentations of hypertriglyceridemia include intermittent episodes of vomiting, diarrhea, and abdominal pain or discomfort. The more severe presentations are pancreatitis (as a secondary or primary disorder), lipemia retinalis, cutaneous xanthomas, seizures, peripheral nerve paralysis (eg, tibial, radial, Horner syndrome), and behavioral changes. Less common presentations include splenomegaly, lipid keratopathy, anemia, and xanthelasma. Signs of DM, hypothyroidism, hyperadrenocorticism, pancreatitis, obesity, PLN, and/or cholestasis are also likely.
How I Diagnose: Hyperlipidemia
12- to 18-hour fasted lipemic serum sample is suggestive of hypertriglyceridemia.2
Clear serum contains <200 mg/dL (2.26 mmol/L).
Turbid serum begins at 200–300 mg/dL (2.26–3.39 mmol/L).
Lactescent (milk-like) serum indicates ~1000 mg/dL (11.3 mmol/L).
Hypercholesterolemia does not cause an increase in serum turbidity because LDL and HDL do not refract light.
Refrigerate sample for 12 hours to determine if the hypertriglyceridemia was caused by chylomicrons or VLDL.
Chylomicrons float to the top (ie, as a creamy layer).
VLDL results in a uniformly turbid sample.
A creamy layer over a cloudy serum layer indicates both are present.
Perform a heparin release test to assess activity level of lipoprotein lipase.
A defect in endothelium lipoprotein lipase is suspected if there is no difference in the pre- and postheparin sample triglyceride concentration (heparin releases lipoprotein lipase and stimulates triglyceride hydrolysis).1
| Consider lipoprotein electrophoresis and ultracentrifugation to identify and quantify the lipoproteins, respectively.
These are not routine.
Normal ranges are not well defined.
|
How I Treat: Hyperlipidemia
Treat hypertriglyceridemia (>500 mg/dL) present in a 12- to 18-hour fasted sample.
Secondary hypertriglyceridemia typically improves with correction of the primary metabolic disorder (eg, pancreatitis, DM, PLN).
Maintain a fasted triglyceride level of <400 mg/dL to minimize signs and complications.
Feed a low-fat (≤30 g/Mcal) diet; reevaluate in 6–8 weeks.
Fat content of low-fat diets expressed as a percentage of dry matter may not coincide with grams of fat/Mcal.
Compare products on a caloric basis (Tables 1 and 2).
Consider individual diet history in diet selection.
If the patient currently eats a high-fat diet, recommend 20–30 g/Mcal diet initially.
If the patient is already on a fat-restricted diet (≤30 g/Mcal), recommend changing to an ultra-low-fat diet (<10 g/Mcal) formulated by a nutritionist.
Consider concurrent diseases.
For diabetic dogs and overweight diabetic cats, consider low-fat/high-fiber therapeutic diets.
For hyperlipidemic, underweight diabetics and PLN cases, commercial diet options are limited but highly specialized diets can be tailored by a nutritionist.
Consider supplementing with fish oil containing EPA and DHA, as hypertriglyceridemia caused by disturbances in the metabolism of endogenous VLDL lipoproteins may not fully respond to a low-fat diet.
For dogs, the recommended omega-3 dose (70–100 mg/kg body weight) may be increased as needed up to the National Research Council safe upper limit (200 mg/kg body weight); no safe upper limit has been determined for cats.<sup3 sup>
Pet foods may include omega-3 fatty acids; however, those using flaxseed meal or oil contain only ALA, and ALA–EPA conversion in dogs and cats is thought to be low (<10%).
Pet foods containing fish oil contain EPA and DHA but typically at low levels.
Supplementing with concentrated fish oil containing EPA and DHA is necessary for therapy.
Consider other possible treatments for lowering VLDLs.
Consider niacin (dogs, 100 mg PO q24h) and gemfibrozil (dogs, 7.5 mg/kg body weight PO q12h; cats, 10 mg/kg body weight PO q12h).1
Both have adverse effects and should be considered only when diet cannot maintain serum triglyceride <500 mg/dL.
Table 1: Canine Foods by Fat*
*Sorted based on fat-per-calorie basis
Table 2: Feline Foods by Fat*
*Sorted based on fat-per-calorie basis
The Take-Home
Hyperlipidemia is common in blood sampled within 12 hours of a meal.
Hypertriglyceridemia is more clinically common than hypercholesterolemia.
Hypertriglyceridemia is caused by disturbances in the metabolism of the chylomicron and/or VLDL lipoprotein.
The disturbance in chylomicron and/or VLDL lipoprotein metabolism is more likely secondary to another ongoing disease process rather than a primary disorder, except in certain breeds.
Clinical signs can be intermittent and not specific to hyperlipidemia.
More severe presentations are more likely to be associated with well-described diseases (eg, endocrine disorders, pancreatitis, obesity, PLN, cholestasis).
Feeding a low-fat diet (≤20–30 g/Mcal) for 6–8 weeks is the first line of treatment with a fasted serum triglyceride goal <400 mg/dL.
Homemade diets with ultra-low-fat content (<10 g/Mcal) can be formulated on an individual basis by a nutritionist.
Supplementing with fatty acids (70–100 mg/kg) may be needed in cases of hyper-VLDL production.
ALA = alphalinolenic acid, DHA = docosahexaenoic acid, DM = diabetes mellitus, DMB = dry matter basis, EPA = eicosapentaenoic acid, HDL = high-density lipoprotein, LDL = low-density lipoprotein, PLN = protein-losing nephropathy, VLDL = very-low-density lipoprotein,
*1 Mcal (megacalorie) = 1000 kcal
REBECCA L. REMILLARD, PhD, DVM, DACVN, is founder of Veterinary Nutritional Consultations, staff veterinary nutritionist at Angell Animal Medical Center in Boston, and clinical nutritionist at North Carolina State University. She is author of numerous articles, co-editor of the 4th and 5th editions of Small Animal Clinical Nutrition, and recently presented on nutrition at the CVC and NC Veterinary Conferences. Dr. Remillard earned her PhD from Colorado State University and her DVM from Tufts University.