Discussion
Age is among the most important cardiovascular risk factors; indeed, many of the cardiovascular risk estimation models are actually based on age.4 ,5 In a cohort of more than 3.6 million individuals undergoing self-referred screening for CVD (ABI, carotid duplex ultrasound and abdominal ultrasound), the prevalence of any vascular disease increased progressively after 40 years of age: from 2% in those aged 40–50 years to 13% among those aged 71–80 years. After adjusting for traditional risk factors, each additional decade of life doubled the risk for vascular disease (OR 2.14 for PAD).10
Moreover, the differential influence of cardiovascular risk factors changes throughout life. In the general population, the Framingham study found that the relative effect of systolic, diastolic and pulse pressure changed with age. In patients younger than 50 years, diastolic blood pressure was the strongest predictor of coronary heart disease (CHD) risk; in those aged 50–59 years old, all three variables contributed equally to CHD risk; among those older than 60 years, pulse pressure was the strongest predictor.11
Our results suggest that age may modulate the effect of risk factors for CVD also in patients with SLE. aPL/APS and higher glucocorticoid load seem to increase the risk of PAD in younger patients, although a multivariant analysis could not be performed. In group 2, an average daily dose of prednisone <7.5 mg was associated with PAD in the univariate but not in the multivariate analysis. Moreover, since more than 75% of patients in this age group were taking low-dose prednisone, this result is likely to be misleading. As age increased, more traditional risk factors such as hypertension and hypercholesterolaemia played a significant role. We identified factors associated with PAD (and, probably, by extension with CVD) hidden by the large influence of age. This could be particularly important among younger patients, in whom the prevalence of arterial disease was low, however very much unrelated to classical cardiovascular risk factors.
This study has a number of limitations, which have been already acknowledged.6 This is a cross-sectional study, with different disease duration among patients. This makes it difficult to fully address the effects of some time-varying variables such as glucocorticoid exposure, lupus activity and cardiovascular risk factors. In addition, almost 90% of our cohort was on hydroxychloroquine, which precludes analysis of the actual effect of this drug. On the other hand, the sizeable number of patients has allowed a differential analysis per different age groups using a large variety of demographic, cardiovascular, lupus-related and therapeutic variables. This is, to our knowledge, the first study of this kind.
Based on our results, a number of practical considerations can be made. First, it is important to regularly check patients with lupus for the presence of aPL, especially in the early phases of the disease, given the possible association with PAD in young patients with SLE. We have previously shown that aPL increase the risk of damage in SLE,12 particularly by the occurrence of thrombotic events.13 Since the addition of low-dose aspirin seems to be protective in aPL-positive patients with SLE according to a recent systematic review,14 the detection of persistently positive aPL should call for early antiplatelet therapy. Second, the doses of prednisone should be reduced as much as possible, especially in young patients, given the possible association with PAD in this group and, in general, with damage in patients with SLE.15 Third, especial attention should be paid to controlling traditional cardiovascular risk factors, especially in older patients.