Clinical Characteristics and Outcomes of Severe and Extreme Hypertriglyceridemia in a Regional Health Service in Israel

Background: Comprehensive data on the prevalence, characteristics and outcomes of severe hypertriglyceridemia (HTG) ≥1,000 mg/dl is limited and is of importance in light of the population increase in the prevalence of metabolic risk factors and novel therapies for HTG which are currently under development.

Methods: Regional electronic database was retrospectively searched between the years 2002-2017 for all adult subjects with first documented episode of severe HTG, further classified as severe (peak TG levels 1,000-1,999 mg/dl), very severe (2,000-2,999 mg/dl) and extreme (≥3,000 mg/dl). Secondary contributing causes and risk factors were evaluated and outcomes including acute pancreatitis, myocardial infarction, stroke and all-cause death were investigated in correlation to the degree of HTG severity.

Results: A total of 3,091 subjects with severe (n=2,590), very severe (n=369) and extreme (n=132) HTG were identified. Mean age was 48±12 years and 73% were males. Alcohol abuse (3.7%), hypothyroidism (8%), obesity (48%) and diabetes (62%) were contributing factors. Severity grade of HTG was associated with younger age and higher rates of hypertension, obesity and diabetes. During a mean follow-up period of 99±58 months, 146 (4.7%) subjects had acute pancreatitis, 145 (4.7%) myocardial infarction and 187 (6%) stroke. A stepwise increase in the risk for acute pancreatitis was noted: compared with severe HTG (reference), the multivariable adjusted hazard ratio was 3.22 (95%CI 2.21-4.70) for individuals with very severe HTG and 5.55 (3.53-8.71) for those with extreme HTG, p<0.0001. In contrast, the extent of severe HTG was not associated with worse cardiovascular outcomes (Figure).

Conclusions: Severe HTG is closely related to the additional constitutes of the metabolic syndrome. The risk for acute pancreatitis is greatly increased in very severe and extreme HTG. Whereas mild to moderate HTG is an established risk factor for myocardial infarction, severe and extreme HTG may not further increase the risk for cardiovascular disease.