Cardiovascular complications of systemic sclerosis: What to look for

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Although macrovascular disease has not typically been regarded as a significant systemic feature in systemic sclerosis, myocardial infarction and stroke are more common in patients with systemic sclerosis than in controls.38,39

Coronary artery disease in systemic sclerosis

Man et al38 reported that the incidence of myocardial infarction in patients with systemic sclerosis was 4.4 per 1,000 persons per year, and the incidence of stroke was 4.8 per 1,000 persons per year, compared with 2.5 per 1,000 persons per year for both myocardial infarction and stroke in healthy controls matched for age, sex, and time of entry.

The Australian Scleroderma Cohort Study39 found a 3-fold higher prevalence of coronary artery disease in systemic sclerosis patients than in controls after factoring in traditional risk factors.

Aviña-Zubieta et al,40 in a cohort of 1,239 systemic sclerosis patients, estimated a hazard ratio (HR) of 3.49 for myocardial infarction and 2.35 for stroke compared with age- and sex-matched controls. Not all of these events were related to macrovascular atherosclerosis—vasospasm and microvascular ischemia may have played significant roles in the etiology of clinical manifestations.

Studies of coronary atherosclerosis in systemic sclerosis are limited. An autopsy study41 of 58 patients with systemic sclerosis and 58 controls matched for age, sex, and ethnicity found that the prevalence of atherosclerosis of small coronary arteries and arterioles was significantly higher in systemic sclerosis patients than in controls (17% vs 2%, P < .01). However, the prevalence of medium-vessel coronary atherosclerosis was similar (48% vs 43%).

Why patients with systemic sclerosis develop atherosclerosis has not yet been determined. Traditional risk factors such as hypertension, dyslipidemia, diabetes mellitus, and obesity are typically no more prevalent in systemic sclerosis patients than in controls,38,42 and thus do not explain the increased risk of atherosclerotic cardiovascular disease. There is some evidence that novel markers of atherosclerotic risk such as homocysteine,43 lipoprotein[a],44 and oxidized low-density lipoprotein45 are more prevalent in systemic sclerosis, but these results have not been substantiated in more extensive studies.

Peripheral artery disease

It remains unclear whether peripheral artery disease is more prevalent in systemic sclerosis patients than in controls.

Individual studies have shown mixed results in comparing carotid artery stenosis between systemic sclerosis patients and controls using carotid duplex ultrasonography,46 the ankle-brachial index,46–48 carotid intima-media thickness,49–54 and brachial flow-mediated dilation.51,53,55–58 A meta-analysis found that the carotid intima and media are significantly thicker in systemic sclerosis patients than in controls,59 and the magnitude of difference is similar to that in other groups at increased cardiovascular risk, such as those with rheumatoid arthritis, diabetes, and familial hypercholesterolemia.60–63

A meta-analysis of brachial artery findings showed significantly lower flow-mediated dilation in systemic sclerosis patients than in controls.64

Overall, given the inconsistency of study results, systemic sclerosis patients should be screened and managed as in other patients with peripheral artery disease, but the clinician should be aware that there may be a higher risk of peripheral artery disease in these patients.


Many patients with systemic sclerosis have right ventricular dysfunction as a consequence of PAH.65 It is important to detect diastolic dysfunction in this population, as it may be an even stronger predictor of death than pulmonary hypertension on right heart catheterization (HR 3.7 vs 2.0).66

Fewer patients have left ventricular dysfunction. In a multicenter study of 570 systemic sclerosis patients, only 1.4% had left ventricular systolic dysfunction on echocardiography, though 22.6% had left ventricular hypertrophy and 17.7% had left ventricular diastolic dysfunction.67 In the European League Against Rheumatism (EULAR) database, the prevalence of reduced left ventricular ejection fraction was 5.4%.68

Though traditional echocardiographic screening suggests the prevalence of left ventricular dysfunction in systemic sclerosis patients is low, cardiac magnetic resonance imaging (MRI) may be more sensitive than echocardiography for detecting subclinical myocardial involvement. Cardiac MRI has been shown to detect evidence of myocardial pathology (increased T2 signal, left ventricular thinning, pericardial effusion, reduced left ventricular and right ventricular ejection fraction, left ventricular diastolic dysfunction, and delayed myocardial contrast enhancement) in up to 75% of systemic sclerosis cases studied.69

Patients with systemic sclerosis should already be undergoing echocardiography every year to screen for PAH, and screening should also include tissue Doppler imaging to detect various forms of left and right ventricular systolic and diastolic dysfunction that may not be clinically apparent.

Though cardiac MRI can provide useful additional information, it is not currently recommended for routine screening in patients with systemic sclerosis.

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