High levels of lipoprotein(a) are associated with an increased risk of myocardial infarction in diabetics

People with diabetes were more likely to have a history of myocardial infarction (MI) if they also had high levels of serum lipoprotein(a), or Lp(a) ), or progressive liver fibrosis, according to a retrospective study using data from the third National Health and Nutrition Examination Survey (NHANES III).

Compared with patients with diabetes and low Lp(a) levels (<10 mg/dL), multivariate analysis showed that the risk of nonfatal MI more than doubled for Lp(a) levels reaching 50 mg/dL or more (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)

Also, advanced liver fibrosis associated with nonalcoholic fatty liver disease (NAFLD) was associated with a 70% higher risk of nonfatal MI (aOR 1.70, 95% CI 1.68-1.72), Avika Atri reported, MD, from Jefferson Einstein Hospital in Philadelphia, at the annual meeting of the American Association of Clinical Endocrinology.

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

However, overall, individuals with advanced liver fibrosis had lower mean Lp(a) levels than those without advanced fibrosis (13.6 vs. 25.9 mg/dL), even among those who had a previous MI (8.6 vs. 34.2 mg/dL).

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

Atri suggested that further research is needed to determine optimal Lp(a) cut-off values for patients with diabetes and NAFLD to improve risk stratification and reduction of ASCVD.

"If I had a patient who met these criteria—diabetes, nonalcoholic fatty liver disease, and heart disease—I would consider adding Lp(a) to diagnostic panel," said session moderator Anunam Kotwal, MD, of the University of Nebraska at Omaha.

He said more information could help determine how aggressively to treat a patient to prevent a heart attack or mitigate further heart problems.

The cross-sectional analysis presented by Atri included a weighted sample of 3,330,795 people with diabetes aged 35 years or older from the NHANES III database (1988–1994) from whom Lp(a) level data were collected ).

Overall, the average age of participants was 62 years, about 59% were women, and the median HbA1c was 7.7%. The prevalence of nonfatal MI was 13.3%, and 18% met criteria for advanced liver fibrosis associated with NAFLD (defined as a Fibrosis-4 score of 2.67).

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

Atri noted that limitations of the study include its cross-sectional nature and that because it is interview-based, there is a possibility of recall bias. In addition, fatal MI could not be assessed for association with Lp(a) or advanced liver fibrosis due to the study design.