Risk Factors Differ by First Cardiovascular Disease Manifestations in Type 1 Diabetes

Cardiovascular system, heart, artwork
Cardiovascular system, heart, artwork
Researchers found that risk factors differ between various first manifestations of cardiovascular disease in patients with type 1 diabetes.

Risk factors differ between various first manifestations of cardiovascular disease (CVD) in patients with type 1 diabetes, according to study results published in Diabetes Research and Clinical Practice

Combining CVD manifestations into a single end point may obscure associations between risk factors and specific outcomes in type 1 diabetes. As such, investigators aimed to determine the risk factors for first manifestations of CVD, including major atherosclerosis events, coronary revascularizations, and soft coronary artery disease, in patients with type 1 diabetes from the Pittsburgh Epidemiology of Diabetes Complications study.

A total of 604 individuals were followed for up to 25 years. Risk factors were assessed at baseline and again at regular intervals for up to 18 years. Major atherosclerosis events included myocardial infarction, stroke, or CVD death. Soft coronary artery disease included angina or ischemic echocardiogram assessment.

A first CVD event occurred in 236 patients (39.1%) over the course of follow-up. Major atherosclerosis events accounted for the majority of events (n=107), followed by soft coronary artery disease (n=91) and revascularization (n=38). Individuals who developed CVD had longer diabetes duration and higher low-density lipoprotein cholesterol (LDL-C) levels compared with those who did not develop CVD, regardless of the type of first manifestation (P <.01 for all).

Triglyceride levels were highest in patients with major atherosclerosis events as the first manifestation of CVD (median, 110 mg/dL; interquartile range [IQR], 73.7-148.4 mg/dL). Albumin excretion rate, white blood cell count, and rates of smoking were also much higher at baseline in patients who developed major atherosclerosis events compared with those who developed any other manifestation (P <.01 for all).

Multivariable modeling identified diabetes duration (hazard ratio [HR], 1.11; 95% CI, 1.08-1.15; P <.0001), natural log of the current albumin excretion rate (HR, 1.32; 95% CI, 1.19-1.48; P <.0001), mean systolic blood pressure (HR, 1.03; 95% CI, 1.01-1.05; P <.0001), baseline white blood cell count (HR, 1.23; 95% CI, 1.12-1.36; P <.0001), baseline LDL-C (HR, 1.01; 95% CI, 1.001-1.013; P =.04), and mean hemoglobin A1c (HbA1c; HR, 1.20; 95% CI, 1.02-1.41; P =.03) as predictors of major atherosclerosis events.

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Many of the same risk factors were predictors of soft coronary artery disease, in addition to current systolic blood pressure (HR, 1.03; 95% CI, 1.01-1.04; P =.0002) and HbA1c (HR, 1.21; 95% CI, 1.06-1.39; P =.005).

Concentrations of LDL-C were highest in patients who experienced revascularization as the first cardiovascular event. In addition to diabetes duration, HbA1c, and baseline estimated glomerular filtration rate, baseline LDL-C (HR, 1.03; 95% CI, 1.02-1.03; P <.0001) was predictive of revascularization.

The researchers noted that the relatively small sample size of the group that experienced revascularization or blockage as a first event represented a limitation of the analysis. In addition, a lack of diversity (98% white population) may limit the generalizability of results.

“[R]isk factors differ for the various first manifestations of CVD in this type 1 diabetes cohort,” the study authors concluded. “These findings underscore the complexity associated with including revascularization in composite CVD endpoints.”

Disclosure: Dr Orchard reported affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.


Miller RG, Orchard TJ, Costacou T. Risk factors differ by first manifestation of cardiovascular disease in type 1 diabetes [published online April 8, 2020]. Diabetes Res Clin Pract. doi:10.1016/j.diabres.2020.108141