The influence of cardiovascular risk-related comorbidities on the development of dilated cardiomyopathy
N J Beelen, S L V M Stroeks, A Paldino, X Li, A B M Heymans, M Dal Ferro, M Merlo, N K Lakdawala, G Sinagra, J A J Verdonschot, S R B HeymansAbstract
Background/introduction
Dilated cardiomyopathy (DCM) is a multifactorial disease in which genetic predisposition, acquired causes and comorbidities may contribute to disease development. To which extent hypertension, diabetes mellitus, and obesity as metabolic comorbidities, individually or combined, may affect DCM development remains largely unknown.
Purpose
This study aims to research the effect of these comorbidities and their potential interplay on the development of DCM.
Methods
Patients with DCM and a control group of unaffected family members were included from nine international centers. The presence of hypertension, diabetes mellitus and obesity prior to diagnosis was assessed in order to evaluate their influence on DCM development and age at diagnosis using multivariable regression analysis.
Results
In total, 3809 patients were included (36.6% female; mean age 51.5 ± 14.0; (likely) pathogenic variant carriers 16.7%), along with 457 unaffected family members (62.9% female; mean age 44.9 ± 15.6; (likely) pathogenic variant carriers 29.2%). Among the patient group, hypertension was present in 33.5%, diabetes mellitus in 13.3%, and obesity (BMI ≥ 30 kg/m2) in 21.7% pre-diagnosis. In the unaffected family members group, hypertension was found in 21.1%, diabetes in 4.1%, and obesity in 18.7% of the cases. Evaluating the effect of the comorbidities on the age of diagnosis showed that hypertension, diabetes, male sex, and genotype negative carriers were independently associated with a later age of onset (Figure 2). Obesity was not associated with a earlier or later age at diagnosis when considered in isolation. However, obesity modified the effect of hypertension and diabetes, with a shift towards an earlier age of onset in patients with combined obesity and hypertension (p<.01) and a similar trend for obesity and diabetes (p=.07) (Figure 2).
Conclusion(s)
When considering the interplay between these comorbidities, obesity appears to accelerate the development of DCM. Hypertension and diabetes were associated with an earlier age of onset, only in the presence of obesity. The underlying mechanisms driving these effects need to be further studied.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.