{'fraction_non_alphanumeric': 0.02675438596491228, 'fraction_numerical': 0.012719298245614035, 'mean_word_length': 4.88516129032258, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Coronary heart disease (CHD) in lupus: round up the usual suspects?

The last 50 years has witnessed a dramatic improvement in survival for patients with systemic lupus erythematosus (SLE). We are now in an era of unprecedented new drug development in this field and the prospects for novel therapeutic approaches in the medium term are very promising indeed. However, many problems continue to challenge the long-term survival and quality of life for patients with SLE. One of the most important of these is accelerated atherosclerosis and premature coronary heart disease (CHD). The scale and impact of this problem is now well described. The pathogenesis, however, remains less clearly defined and the influence of certain, seemingly obvious, candidates are still far from completely understood. Urowitz et al. published the initial case series from Toronto in 1976 suggesting that late mortality in SLE was strongly associated with CHD when SLE disease activity was low or absent. A later analysis of a larger series of deaths from the same cohort identified the presence of significant atheroma in about 50% of patients who had a post-mortem, regardless of the primary cause of death. More recently, Ward reported in a large hospital discharge database that hospitalizations due to myocardial infarction (MI) were 8.5 times more frequent in women with lupus than expected for the general population. Similarly, Manzi et al. compared the incident rates for new MI/angina in the Pittsburgh cohort against data from the Framingham Offspring Cohort. Overall, women with lupus had a 5-fold increased risk of events. Importantly, in the 35–44 year old age bracket the rate ratio for MI was 52-fold higher in SLE patients. As suggested by post-mortem studies the burden of atheroma has also been confirmed to be increased in SLE. Roman et al. recently compared the prevalence of carotid plaque in women with SLE compared to community controls. In this study, 37% of SLE patients compared to 15% of controls had evidence of carotid plaque. Overall, the relative risk for plaque was 2.4 (95% CI, 1.7–3.6) for SLE increasing to 5.6 in women ,40 years old. Similarly, using coronary calcification scores on electron beam computed tomography, Asanuma et al. found that the prevalence of coronary calcification and the mean coronary calcium scores were both significantly increased in lupus patients. In both studies the increased atherosclerotic burden was particularly notable in younger women with SLE. Other studies using different methods to detect subclinical atherosclerotic disease have also confirmed the high burden of atherosclerosis and premature CHD in SLE. The early age at which this develops demonstrates that, like diabetes mellitus, women with lupus lose the usual premenopausal protection against atherosclerosis development. As a result, the average age of the first CHD-event is in the late 40s. Since the average age of menopause in SLE is in the mid 40s, this means that many events occur in the periand early postmenopausal period. As such, this period may represent a period of particular risk in SLE in which women should be carefully assessed and screened. While premature CHD is now an accepted phenomenon, our knowledge of why SLE is associated with atherosclerosis is less certain. Bulkley et al. first suggested that this phenomenon is strongly associated with steroid therapy and it is generally assumed that steroid therapy must be a major contributor to CHD development. The evidence that steroids are the main driving force is however less than clear. In several cohort studies, duration of steroid exposure or cumulative steroid dose has been identified as a risk factor for future events. In contrast, Roman et al. noted that SLE patients with carotid plaque may have had less average daily steroid exposure and no relation to steroid use has been seen in several other studies. Steroid use is, however, notoriously difficult to study and it is not clear which measure of steroid exposure (e.g., duration, peak dose, cumulative dose) may be the most relevant to CHD risk. The relationship to underlying disease activity also needs to be considered. MacGregor et al. found, for example, that in Correspondence: Dr Ian N Bruce, Senior Lecturer and Consultant in Rheumatology, University of Manchester, Rheumatism Research Centre, Central Manchester and Manchester Children’s University Hospitals NHS Trust, Oxford Road, Manchester M13 9WL, UK. E-mail: ian.bruce@ man.ac.uk Received and accepted 14 April 2004 Lupus (2004) 13, 557–560