A New Marker of Silent Cardiovascular Disease in Diffuse Systemic Sclerosis

Turiel M, Gianturco L, Ricci C, et. al. Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross-sectional study.Arthritis Care Res (2013) 65: 274–280. doi: 10.1002/acr.21819

 
Patients with diffuse systemic sclerosis (SSc) and no clinical evidence of cardiovascular disease (CVD) may, in fact, have subclinical CVD and atherosclerosis, and it is detectable. This is the conclusion of a small pilot study from Italy, which showed that elevated plasma levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor important in the atherosclerotic process, may be a unique indicator of cardiovascular risk in systemic sclerosis (SSc).

The immune-inflammatory response that injures vascular endothelial cells in SSc may in turn increase the risk of cardiovascular disease (CVD), but patients may show no clinical indication of a cardiovascular problem despite early atherosclerosis and endothelial damage, evident only with such a marker.

The study assessed CVD risk among 20 consecutive outpatients with diffuse SSc (2 men and 18 women, mean age 53) who had neither a clinical history nor signs of coronary artery disease, arrhythmia, or other cardiac diseases. They were compared to 20 healthy matched controls. Among the SSc patients, the mean disease duration (time since the first appearance of non–Raynaud’s or other symptoms) was 50 months.

The majority of patients were being treated with azathioprine (mean dose 150 mg/day), two were on methotrexate, and another on mycophenolate mofetil. Seven patients were also taking low-dosage nifedipine because of Raynaud’s phenomenon.

In addition to ADMA, a known marker for atherosclerosis in chronic inflammatory disorders, the researchers looked at coronary flow reserve (CFR), previously established as an indicator of disordered coronary macrocirculation and microcirculation in systemic autoimmune diseases. Standard clinical tests along with blood pressure were used to assess CVD risk. 

The researchers found impaired CFR and increased plasma ADMA levels among the SSc patients. While impaired CFR is established as a highly sensitive diagnostic marker, they suggest that elevated ADMA may be “a newly defined risk factor” among patients with SSc and other systemic autoimmune diseases. 

Additionally, all arterial wall measurements in patients with diffuse SSc were significantly different than in the healthy controls, and there were also significant elevations in both right and left carotid intima-media thickness and arterial stiffness, compared to controls.