Cardiovascular manifestations in systemic inflammatory diseases

Abstract

Systemic inflammatory diseases, including those of rheumatology and dermatology, are associated with increased cardiovascular events. Evidence demonstrates that the chronic systemic inflammation associated with these diseases plays a pivotal role in all stages of atherosclerotic plaque formation, from initiation of the fatty streak to plaque rupture and consequent acute coronary syndrome. Although a number of studies have evaluated the cardiovascular manifestations in systemic inflammatory disease, this thesis offers additional observations, including the vascular atherosclerotic pattern, the pathogenesis of premature atherosclerosis and the use of coronary calcification as a predictor of adverse cardiovascular outcome.

The work is divided into four sections. Section I provides an overview of the cardiovascular manifestation of systemic inflammatory diseases and the patients and methods of the current thesis. The objective of Section II is to evaluate the pattern of cardiovascular manifestation, in particular systemic vascular calcification and cardiac valve calcification in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and psoriasis, using multi-detector computed tomography (MDCT) and carotid intima-media thickness (c-IMT). It was found that both patients with RA, SLE and psoriasis had a greater prevalence and extent of vascular calcification compared with age and gender matched controls. Moreover, both aortic valve calcification (AVC), mitral valve calcification (MVC) was found to be more prevalent in patients with RA and SLE than controls. Interestingly, the presence of MVC, but not AVC, independently predicted the occurrence of premature atherosclerosis with arterial calcification in these patients.

Section III evaluates the potential underlying mechanisms that lead to cardiovascular manifestations in patients with systemic inflammatory disease. Bone marrow-derived endothelial progenitor cells (EPCs) play an important role in the maintenance of endothelial integrity and hemostasis. The relationship between the circulating EPCs and subclinical coronary atherosclerosis as determined by coronary calcification in RA patients nonetheless remains unclear. The study results demonstrated that RA patients with coronary atherosclerosis have significantly lower levels of CD133/KDR+ and CD133+ EPCs than those without. In addition to older age, lower levels of circulating CD133/KDR+ EPCs also predicted occurrence of coronary atherosclerosis. As with RA and SLE, psoriasis is associated with premature atherosclerosis, although the underlying mechanism remains unclear. The aim of the study was therefore to investigate the relationship of disease activity and systemic inflammation with macrovascular and microvascular function in patients with psoriasis. The results demonstrated that patients with psoriasis have increased arterial stiffness, but not microvascular dysfunction compared with healthy controls. More importantly, high-sensitivity C reactive protein positively correlated with, and independently predicted, arterial stiffness.

Section IV explores the prognostic value of a surrogate marker of atherosclerosis, coronary calcium score (CCS), in patients with RA and SLE. A total of 152 patients with RA (n=85) and SLE (n=69), and 106 healthy controls underwent MDCT to measure CCS. All patients were prospectively followed up for major cardiovascular events for a mean period of 4.3 years. The result demonstrated that presence of CCS >100 predicted the occurrence of a major cardiovascular event independent of other risk factors in RA and SLE patients.