Primary Hyperlipidemia

4. Primary Hyperlipidemia

Once it is verified that hyperlipidemia occurs after a 10- to 12-hour fast, and all possible causes of secondary hyperlipidemia have been ruled out, a presumptive diagnosis of primary hyperlipidemia is made. Primary hyperlipidemias are usually genetically determined. In the dog, several different types of primary hyperlipidemia have been observed, including idiopathic hyperchylomicronemia, idiopathic hypercholesterolemia, and idiopathic hyperlipoproteinemia; however etiologies of these conditions have not been well established. It is likely that with further research, many different primary syndromes with subtle differences in etiology will be identified in dogs as in humans.

Idiopathic Hyperchylomicronemia

A pure hyperchylomicronemia has been reported in a 28 day old mixed-breed puppy (Baum et al., 1969). This puppy was the smallest in a litter of three, was irritable and weak, with a palpably enlarged liver. Blood had the appearance of "cream-of-tomato" soup, and after cold centrifugation, a lactescent upper layer was observed with a triglyceride concentration of 830 mg/dL, and cholesterol concentration of 312 mg/dL. The administration of heparin sulfate did not clear the plasma from this puppy, and a presumptive diagnosis of lipoprotein lipase deficiency was made. There was no evidence of diabetes mellitus, but other causes of secondary hyperlipemia were not ruled out. The puppy died of pneumonia at 33 days of age. At necropsy, the liver was enlarged, yellow in color, with marked accumulation of lipid within hepatocytes.

Idiopathic Hypercholesterolemia

In 15 clinically healthy Briards with unexplained fasting hypercholesterolemia, serum was not hyperlipemic, and serum triglyceride concentrations were normal in all dogs (Watson et al., 1993). Causes of secondary hyperlipidemia were ruled out. Lipoprotein electrophoresis revealed a marked increase in α-migrating lipoproteins (HDL1) with no other abnormalities. This abnormality is unlike those reported in dogs with idiopathic hyperlipoproteinemia where serum cholesterol and triglyceride concentrations are both increased.

In the Briard, idiopathic hypercholesterolemia may be related to the development of retinal pigment epithelial dystrophy. (© Labat).

Idiopathic hypercholesterolemia has also been noted in a miniature Bull Terrier (Schenck, unpublished observation). This dog was clinically healthy with unexplained fasting hypercholesterolemia and normal serum triglyceride concentration. Serum was not hyperlipemic, and the only abnormality seen on lipoprotein electrophoresis was an accumulation in α2-migrating lipoprotein (HDL1).

Idiopathic or Primary Hyperlipoproteinemia

Primary hyperlipoproteinemia with similar characteristics has been observed in a number of dog breeds including the miniature Schnauzer, Shetland sheepdog, Beagle, miniature Poodle, Cocker Spaniel, English Cocker Spaniel, and mixed-breed dog. Miniature Schnauzers appear to have a higher incidence of primary hyperlipoproteinemia, however any breed of dog may be affected. Clinical signs associated with primary hyperlipoproteinemia may include abdominal pain (presumptively due to pancreatitis) and seizures (Rogers et al., 1975a), but many dogs exhibit no obvious clinical signs.

In a study of 5 miniature Schnauzers diagnosed with idiopathic hyperlipoproteinemia, all dogs had moderately increased serum cholesterol concentrations, and moderate to marked increase in serum triglyceride concentration (Rogers et al., 1975a). Increases in β-migrating and α2-migrating lipoproteins on lipoprotein electrophoresis were the most consistent findings. Two of 5 dogs had an increase in chylomicrons. Injection of heparin caused shifting of lipoproteins in two dogs, but only cleared the serum of one dog.

In another study of 6 healthy miniature Schnauzers diagnosed with idiopathic hyperlipoproteinemia, 4 of 6 had a history of recurrent episodes of hyperlipidemia (Whitney et al., 1993). On lipoprotein electrophoresis all 6 dogs had increased β-migrating lipoproteins, predominantly due to an increase in VLDL as determined by density gradient ultracentrifugation. Four of 6 had an increase in chylomicrons at the origin.

Miniature Schnauzers appear to present a high incidence of primary hyperlipo-proteinemia, although no breed is safe. (© Hermeline).

Two related Beagles with idiopathic hyperlipoproteinemia also exhibited an increase in β-migrating and α2-migrating lipoproteins on lipoprotein electrophoresis (Wada et al., 1977). Both dogs were clinically normal, showed increased serum cholesterol and triglyceride concentrations, and had a common sire.

Potentially two different abnormalities may exist in a study of 62 Shetland sheepdogs with hypercholesterolemia (Sato et al., 2000). Both mean plasma cholesterol and triglyceride concentrations were increased in these dogs, though no correlation between cholesterol and triglyceride was observed. In Shetland sheepdogs with plasma cholesterol concentrations greater than 250 mg/dL, an increase in α2-migrating lipoproteins was noted, similar to that seen in Briards. In dogs with plasma cholesterol concentrations greater than 500 mg/dL, an increase in β-migrating lipoprotein, mostly due to LDL was also observed. The plasma triglyceride concentration in the group of dogs with plasma cholesterol concentration greater than 500 mg/dL was not reported.

In 10 clinically healthy dogs of various breeds diagnosed with primary hyperlipoproteinemia, mean serum cholesterol concentration was 532 ± 256 mg/dL, and mean serum triglyceride concentration was 1955 ± 2193 mg/dL (Schenck, 2002). A group of healthy, non-hyperlipidemic control dogs had mean serum cholesterol and triglyceride concentrations of 153 ± 17 mg/dL and 56 ± 13 mg/dL respectively. On lipoprotein electrophoresis the most consistent finding was an increase in β-migrating lipoproteins, and percentages of chylomicrons and α2-migrating lipoproteins were similar in both groups (Figure 9). Lipoprotein lipase activity was significantly decreased in dogs with primary hyperlipoproteinemia, with a mean of 35±8 nmol free fatty acids released/min/mL compared to 110 ± 10 nmol free fatty acid released/min/mL in the control dogs. Hepatic lipase activity was significantly increased in dogs with primary hyperlipoproteinemia, with a mean of 37±10 nmol free fatty acid released/min/mL compared to 28±5 nmol free fatty acid released/min/mL in the control dogs. This study presents the first potential etiology for "idiopathic" hyperlipoproteinemia. Decreased activity of lipoprotein lipase leads to decreased clearance of VLDL and chylomicrons, and hepatic lipase may be increased in a compensatory role. A decrease in lipoprotein lipase activity in 8 miniature Schnauzers with primary hyperlipoproteinemia was also observed in a subsequent study (Jaeger, 2003).

Figure 9. Densitometric tracing of lipoprotein electrophoretogram of a dog with primary hyperlipoproteinemia.