Early morphologic and functional changes of atherosclerosis in systemic sclerosis-a systematic review and meta-analysis

Rheumatology (Oxford). 2016 Dec;55(12):2119-2130. doi: 10.1093/rheumatology/kew236. Epub 2016 Aug 25.


Objective: Cardiopulmonary manifestations have an important impact on the life expectancy of SSc patients. Functional and morphological macrovascular changes may appear early before the development of ischaemic symptoms. Several non-invasive methods are used in cardiovascular risk assessment. Heterogeneous data are available regarding these in SSc. We aimed to perform a systematic review and meta-analysis to characterize the importance of atherosclerosis in SSc.

Methods: A systematic literature search was performed to identify controlled studies on carotid intima-media thickness, flow- or nitrate-induced vasodilatation (flow-mediated dilatation, nitroglycerine-mediated dilatation), pulse wave velocity, augmentation index and ankle-brachial pressure index. Outcomes were pooled with the random-effects model.

Results: Thirty-five studies comprising a total of 1292 SSc patients qualified. Intima-media thickness, pulse wave velocity and ankle-augmentation index were higher and flow-mediated dilatation lower in SSc patients [standardized mean difference (SMD) 0.65 (95% CI: 0.29, 1.01), 0.62 (95% CI: 0.35, 0.88), 0.96 (95% CI: 0.45, 1.47) and -0.68 (95% CI: -1.39, -0.34), respectively, P < 0.01 for each]. Nitroglycerine-mediated dilatation and ankle-brachial pressure index were lower, but not significantly [SMD: -0.16 (95% CI: -0.50, 0.18) and -0.39 (95% CI: -0.91, 0.13), respectively]. Data showed high to moderate inconsistency and significant heterogeneity. Meta-regression analysis of the SMD and the disease duration found a regression coefficient of 0.086, P = 0.014, confirming that parameters of the included SSc population may have contributed to the heterogeneity.

Conclusion: Meta-analysis of the published observational studies confirms that abnormalities attributable to macrovascular involvement are significantly more prevalent in SSc patients compared with controls. Considering the increasing importance of cardiovascular disease in SSc, a more widespread use of cardiovascular risk assessment is warranted.

Keywords: ankle-brachial index; arterial stiffness; augmentation index; carotid intima–media thickness; flow-mediated dilatation; meta-analysis; nitroglycerine-mediated dilatation; pulse wave velocity; scleroderma; systemic sclerosis.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Ankle Brachial Index
  • Atherosclerosis / etiology*
  • Atherosclerosis / pathology
  • Atherosclerosis / physiopathology
  • Blood Flow Velocity / physiology
  • Carotid Intima-Media Thickness
  • Female
  • Humans
  • Male
  • Middle Aged
  • Observational Studies as Topic
  • Pulse Wave Analysis
  • Risk Assessment
  • Scleroderma, Systemic / complications*
  • Scleroderma, Systemic / pathology
  • Scleroderma, Systemic / physiopathology
  • Vascular Stiffness / physiology
  • Vasodilation / physiology