Liver Disease, High Lipoprotein(a) Tied to Higher MI Risk in Diabetes Patients

NEW ORLEANS — Individuals with diabetes were more likely to report a history of myocardial infarction (MI) if they also had high levels of serum lipoprotein(a), or Lp(a), or advanced liver fibrosis, a retrospective study using data from the National Health and Nutrition Examination Survey (NHANES) III found.

Compared with diabetes patients with the lowest Lp(a) levels (<10 mg/dL), multivariate analysis showed that the risk for a non-fatal MI more than doubled when levels reached 50 mg/dL, a level that current guidelines consider to be elevated, and beyond (P<0.001 for all):

• 50-99 mg/dL: adjusted odds ratio (aOR) 2.17 (95% CI 2.15-2.19)
• 100-149 mg/dL: aOR 4.20 (95% CI 4.14-4.27)
• ≥150 mg/dL: aOR 6.36 (95% CI 6.17-6.54)

As well, advanced liver fibrosis associated with non-alcoholic fatty liver disease (NAFLD) was linked with a 70% higher risk for a non-fatal MI (aOR 1.70, 95% CI 1.68-1.72), reported Avica Atri, MD, of Jefferson Einstein Hospital in Philadelphia, at the annual American Association of Clinical Endocrinology meeting here.

Patients who self-reported a history of MI had higher Lp(a) levels than those who did not report an MI (mean 30.7 vs 24.2 mg/dL, respectively) and were more likely to have advanced liver fibrosis (13.5% vs 4.5%).

Yet overall, the individuals with advanced liver fibrosis tended to have lower mean Lp(a) levels than those without advanced fibrosis (13.6 vs 25.9 mg/dL), even among the subset with a prior MI (8.6 vs 34.2 mg/dL).

Lp(a) is produced by the liver, explained Atri, and the levels circulating in the body are determined by genetics. It is an established independent risk factor for atherosclerotic cardiovascular disease (ASCVD), and while growing evidence suggests NAFLD is linked with heart disease as well, the relationship between Lp(a), NAFLD, and the risk of MI has not been well studied in patients with diabetes mellitus.

Atri suggested that further work is needed to determine optimal cut-offs of Lp(a) for patients with diabetes and NAFLD to improve risk stratification and mitigation of ASCVD.

“If I had a patient that met these criteria — diabetes and non-alcoholic fatty liver disease and heart disease — I think I would consider adding Lp(a) to the diagnostic panel,” said session moderator Anupam Kotwal, MD, of the University of Nebraska in Omaha.

He told MedPage Today that the additional information could inform how aggressively he would treat the patient, to prevent a heart attack or to mitigate further cardiac problems.

The cross-sectional analysis presented by Atri included a weighted sample of 3,330,795 people with diabetes ages 35 and older from the NHANES III database (1988 to 1994) who had Lp(a) data collected.

Overall, the mean participant age was 62 years, about 59% were women, and the median HbA1c was 7.7%. Prevalence of a non-fatal MI was 13.3%, and 18% met the criteria for advanced liver fibrosis associated with NAFLD (defined as a score of 2.67 on the Fibrosis-4 scale).

A higher proportion of patients in the MI group had Lp(a) levels over 50 mg/dL (about 30% vs 19% in those without an MI).

Atri noted that limitations of the study included its cross-sectional nature and that because it is based on interviews, there is possibility of recall bias. Furthermore, fatal MIs could not be assessed for an association with Lp(a) or advanced liver fibrosis given the study design.

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