Antibiotic Use, LPS Activity Levels Help Predict CHD Risk in Diabetics

This article originally appeared on Practical Cardiology's sister site, EndocrinologyNetwork.com.

Johan Rasmus Simonsen, MD

Results of an analysis of prospective cohort data from Europe suggests increased antibiotic use and bacterial lipopolysaccharide activity levels could help predict risk of coronary heart disease in type 1 diabetics.

Using data from the Finnish Diabetic Nephropathy Study, investigators determined each annual antibiotic purchase was associated with a 21% increase in risk of coronary heart disease among patients in the study.

"In broader terms, the present study demonstrates how infections associate with the development of late diabetic complications and perhaps even more importantly, how infections associate with the development of coronary heart disease, as the latter relationship has been disputed during recent years," said lead investigator Johan Rasmus Simonsen, MD, of the Folkhälsan Research Center, in Finland, in a statement. "Interestingly, in our study this association to incident coronary heart disease was seen specifically with antibiotic purchases, making the potential pathophysiologic mechanisms behind this finding intriguing and warranting further studies."

The Finnish Diabetic Nephropathy Study is an ongoing prospective study including more than 3500 diabetic patients aimed at identifying risk factors for diabetic complications. With recent studies shining a spotlight on associations between infections and inflammation with cardiovascular disease, investigators sought to purchase data from the study to assess whether infections and antibiotic use were associated with risk of coronary heart disease in type 1 diabetics.

From the study, investigators identified a cohort of 3781 patients with type 1 diabetes recruited from more than 90 centers across Finland. Of the 3781-patient cohort, 370 patients experienced a coronary heart disease event during the follow-up.

For the purpose of their analysis, coronary heart disease was defined as a group of incident cardiovascular events including fatal or non-fatal myocardial infarction, coronary artery bypass surgery, or percutaneous coronary intervention, which were identified through national hospital discharge register data. National register data related to outpatient antibiotic purchases were used to identify infections among patients. Additionally, investigators obtained data related to bacterial lipopolysaccharide (LPS) activity from serum samples taken at baseline.

Among those included in the study, 75.8% had a normal albumin exertion rate at baseline—14.9% had microalbuminuria and 9.3% had macroalbuminuria. Additionally, investigators pointed out 9.1% of patients diabetic neuropathy progress from baseline to a more advanced stage during the follow-up period, which lasted a mean of 13.7 years for the entire 3781-patient cohort.

Upon analysis, investigators found patients who experienced an incident coronary heart disease event had a higher mean number of antibiotic purchases per follow-up year compared to type 1 diabetics who did not experience such an event (1.34; 95% CI, 1.16-1.52 vs 0.79; 95% CI 0.76-0.82], P < 0.001),. Results also indicated higher levels of LPS activity (0.64 [0.60-0.67], vs 0.58 EU mL_1 [0.57-0.59], P <.001) were present among those with an incident coronary heart disease event.

Investigators pointed out results of a multivariable-adjusted Cox proportional hazards model suggested the mean number of antibiotic purchases per follow-up year was an independent risk factor for incident coronary heart disease in the study population (HR 1.21, 95% CI; 1.14-1.29, P <.0001). Furthermore, increased LPS activity was considered a risk factor for incident coronary heart disease when adjusting for static confounders, which included sex, age, age at onset of diabetes, history of smoking, and stage of diabetic nephropathy (HR 1.93; 95% CI, 1.34-2.78, P <.001).

This study, titled “The association between bacterial infections and the risk of coronary heart disease in type 1 diabetes,” was published in the Journal of Internal Medicine.