Epidemiologic Data Suggest Ceramide Link To CVD Risk

Epidemiologic Data Suggest Ceramide Link To CVD Risk
Key Takeaways

In American Indians (Native Americans) with type 2 diabetes , higher plasma levels of ceramide-16 (ceramide with acylated palmitic acid) associated with a higher rate of cardiovascular disease events, especially CVD events associated with atherosclerosis.
The results also suggested other possible associations between plasma levels of sphingolipids and incident CVD events, but the study applied a Bonferroni correction to adjust for multiple comparisons that set a high bar for statistically significant associations with a P value of no greater than 0.0063, based on P less than 0.05/8 for the eight sphingolipid species assessed.

Why This Matters

Prior results had independently linked plasma ceramides and sphingomyelins to diabetes risk, glucose levels, insulin levels, and CVD outcomes, but uncertainty remains whether individual sphingolipid species contribute to CVD risk in people with type 2 diabetes.

Study Design

The study included people with type 2 diabetes enrolled in two related population-based longitudinal studies that examined CVD incidence and risk factors in several American Indian communities in Arizona, North Dakota, South Dakota, and Oklahoma: the Strong heart disease and the Strong Heart Family Study.
The analysis focused on a prospective cohort of 597 participants in the Strong Heart Family Study with full data available on sphingolipids and CVD events who had 116 incident CVD events over a median 14-year follow-up.
The researchers defined CVD events as a first occurrence of myocardial infarction , ischemic stroke, atherosclerotic Cardiovascular disease, or heart failure.
Analysis of data from the Strong Heart Study used a nested case-control design with 267 participants, including 78 with CVD events during a median 3.8-year follow-up and 189 controls who did not have an incident CVD event.

Key Results

In a multivariate model, two investigated sphingolipids significantly associated with greater risk for incident atherosclerotic CVD (ASCVD) events: ceramide (Cer)-16 (hazard ratio [HR], 2.01; P = .0006) and Cer-20 (HR, 1.70; P = .00004).
After adjustment for other sphingolipids, neither of these sphingolipids met the Bonferroni threshold for significance. The evidence suggested a possible association between Cer-16 and higher ASCVD risk (HR, 2.26; P = .0276), but not Cer-20 (HR, 1.42; P = .2180).
The data showed no significant association between the investigated sphingolipids and incident heart failure.
In a meta-analysis of the two cohorts, which collectively included 194 people with incident CVD events, each doubling of plasma Cer-16 significantly associated with a 54% increased rate of composite CVD events.
Higher plasma levels of sphingomyelin species with a very-long-chain saturated fatty acid associated with decreased CVD risk but none met the prespecified threshold for statistical significance.

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