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Outcomes of Severe, Very Severe, and Extreme Hypertriglyceridemia
Study Questions:
What are the causes and outcomes of severe to extreme hypertriglyceridemia (HTG)?
Methods:
A regional database in Israel was retrospectively analyzed for subjects with severe HTG. Adverse outcomes were investigated in correlation with HTG severity, with follow-up initiating at first documentation of HTG >1000 mg/dl. The number of subjects with a customarily 12-hour fasting lipid profile varied from 192,707 in 2002 to 312,623 in 2017. Possible contributing factors included obesity, diabetes, excessive alcohol, hypothyroid, renal failure, and fatty liver disease and outcome variables included death, myocardial infarction (MI), cerebral vascular accident (CVA), and acute pancreatitis. Multivariate analysis of the association of severity grade of HTG with long-term adverse outcomes was performed using the Cox proportional hazards model.
Results:
The yearly incidence of severe HTG ranged from 0.093% to 0.254% of the yearly population. A total of 3,091 subjects with severe (peak triglycerides 1000–1999 mg/dl; n = 2,590), very severe (2000–2999 mg/dl; n = 369), and extreme (>3000 mg/dl; n = 132) HTG were identified. Mean age at first documented HTG was 48 ± 12 years, with 73% males. Obesity (48%) and diabetes (62%) were the main contributing factors, and hypertension (56%) and smoking (30%) were the other commonly associated risk factors. During follow-up (median 101 months), 4.7% subjects had pancreatitis, 4.7% MI, and 6% CVA. Compared with severe HTG, the multivariate-adjusted hazard ratio for pancreatitis was 3.22 for individuals with very severe HTG and 5.55 for those with extreme HTG (p < 0.0001). In contrast, the extent of HTG severity at these levels was not associated with worse cardiovascular outcomes or death. Most subjects (81%) achieved triglyceride levels <500 mg/dl, which was associated with lower risk for developing pancreatitis, but not MI or CVA.
Conclusions:
Severity of HTG is closely related to cardiometabolic conditions, with a stepwise increase in the risk for pancreatitis, particularly if not attaining reduced triglyceride levels during the follow-up. In contrast, whereas mild-to-moderate HTG is a known established cardiovascular risk factor, very severe and extreme HTG may not further increase the risk for MI, stroke, or mortality.
Perspective:
Large triglyceride risk chylomicron and very low-density lipoprotein (VLDL) particles are too large to penetrate the endothelium and result in plaque. But there is evidence that familial HTG is associated with increasing risk of MI and strokes thought related to the smaller VLDL remnant particles that may enhance the size of fatty plaques, and possibly increase inflammatory cytokines and thrombosis. This study was probably underpowered to conclude that HTG <500 mg/dl is not associated with a risk of MI, CVA, and death.
Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Hypertriglyceridemia, Lipid Metabolism, Hypertension, Smoking
Keywords: Diabetes Mellitus, Dyslipidemias, Endothelium, Hypertension, Hypertriglyceridemia, Lipoproteins, VLDL, Metabolic Syndrome, Myocardial Infarction, Obesity, Pancreatitis, Primary Prevention, Renal Insufficiency, Risk Factors, Smoking, Stroke, Thrombosis, Triglycerides
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