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- SUBJECTS AND METHODS
- AUTHOR CONTRIBUTIONS
The study included 5,267,589 elective hospitalizations with a noncardiac principal procedure among women with and without SLE between 1998 and 2002, of which 3,640,994 were categorized as low-, 1,513,597 as intermediate-, and 112,998 as high-risk procedures. Table 1 shows the characteristics of the study population by procedure risk and the presence or absence of SLE.
Table 1. Characteristics of hospitalized women by procedure risk level and lupus statusa
| ||Low risk (n = 3,640,994)||Intermediate risk (n = 1,513,597)||High risk (n = 112,998)|
|SLE (n = 13,263)||Non-SLE (n = 3,627,731)||Pb||SLE (n = 6,237)||Non-SLE (n = 1,507,360)||Pb||SLE (n = 1,019)||Non-SLE (n = 111,979)||Pb|
|Age, mean ± SE years||49.3 ± 0.6||45.1 ± 0.5||< 0.001||50.3 ± 0.5||54.7 ± 0.2||< 0.001||48.9 ± 1.3||67.1 ± 0.3||< 0.001|
|Hypertension||29.0 (1.1)||16.7 (0.5)||< 0.001||34.0 (1.4)||28.1 (0.4)||< 0.001||32.8 (3.4)||45.8 (0.7)||< 0.001|
|CAD||10.6 (0.7)||8.1 (0.4)||< 0.001||5.5 (0.7)||4.7 (0.1)||0.26||13.5 (2.3)||28.0 (0.7)||< 0.001|
|CHF||7.7 (0.6)||5.4 (0.2)||< 0.001||3.2 (0.5)||2.0 (0.1)||0.02||9.4 (1.9)||14.6 (0.4)||0.01|
|Valvular heart disease||0.8 (0.2)||0.6 (0.1)||0.25||0.6 (0.2)||0.3 (0.0)||0.13||3.4 (1.4)||6.0 (0.4)||0.07|
|DM||12.1 (0.7)||8.8 (0.3)||< 0.001||8.1 (0.7)||10.4 (0.1)||0.002||14.8 (2.9)||28.2 (0.7)||< 0.001|
|CKD||3.6 (0.5)||0.5 (0.03)||< 0.001||3.9 (0.8)||0.3 (0.03)||< 0.001||26.4 (3.9)||3.8 (0.4)||< 0.001|
Among women who underwent a low-risk principal procedure, women with SLE were older than the women in the comparison group, whereas among women in the intermediate- and high-risk principal procedure strata, women with SLE were younger (Table 1). Although women with SLE who underwent a high-risk procedure were more likely to have chronic kidney disease, there was a greater prevalence of coronary artery disease, diabetes mellitus, hypertension, valvular heart disease, and CHF among women without SLE. Coronary artery disease was more common among women with SLE in the low-risk principal procedure stratum but less common in the high-risk principal procedure stratum than women in the comparison group. Chronic kidney disease was more common in women with SLE than in the comparison group in each principal procedure risk stratum. Diabetes mellitus was more common among women with SLE in the low-risk principal procedure stratum but less common in the intermediate- and high-risk principal procedure strata than women in the comparison group. Hypertension and CHF were more common in women with SLE than in the comparison group in the low- and intermediate-risk principal procedure strata.
Perioperative all-cause mortality
Among women who underwent a low-, intermediate-, and high-risk principal procedure, there were 38,020 (1.04%), 5,444 (0.36%), and 3,333 deaths (2.95%), respectively. All-cause in-hospital mortality was more common among women with SLE compared to women without SLE who underwent a low-risk principal procedure (224 [1.69%] versus 37,796 [1.04%]; P = 0.02) or a high-risk principal procedure (54 [5.28%] versus 3,279 [2.93%]; P = 0.05), whereas the difference among persons with an intermediate-risk principal procedure was not statistically significant (33 [0.52%] versus 5,412 [0.36%]; P = 0.37).
Table 2 shows the odds of all-cause mortality among persons with a principal procedure. The odds of all-cause mortality were greater in women with SLE who underwent either a low- or high-risk principal procedure relative to the women in the comparison group, which persisted after adjusting for potential confounders. For women who underwent an intermediate-risk procedure, the odds of all-cause mortality did not differ significantly in women with SLE compared to women without SLE.
Table 2. Odds of adverse perioperative events by principal procedure riska
| ||All-cause mortality||Composite CVD event|
|Low-risk procedures|| || || || |
|Model A||1.00||1.64 (1.09–2.44)||1.00||1.50 (1.14–1.98)|
|Model B||1.00||1.91 (1.26–2.91)||1.00||1.73 (1.30–2.31)|
|Model C||1.00||1.56 (1.01–2.39)||1.00||1.42 (1.06–1.90)|
|Model D||1.00||1.54 (1.00–2.37)||1.00||1.40 (1.04–1.87)|
|Intermediate-risk procedures|| || || || |
|Model A||1.00||1.46 (0.63–3.35)||1.00||0.81 (0.31–2.10)|
|Model B||1.00||2.27 (0.99–5.21)||1.00||1.38 (0.52–3.63)|
|Model C||1.00||1.78 (0.78–4.09)||1.00||1.05 (0.39–2.83)|
|Model D||1.00||1.90 (0.83–4.36)||1.00||1.06 (0.39–2.84)|
|High-risk procedures|| || || || |
|Model A||1.00||1.85 (0.99–3.45)||–||–|
|Model B||1.00||2.98 (1.56–5.69)||–||–|
|Model C||1.00||2.65 (1.40–4.99)||–||–|
|Model D||1.00||2.52 (1.34–4.75)||–||–|
Composite CV outcome
A total of 57,285 (1.57%), 5,831 (0.39%), and 2,385 composite CVD events (2.11%) occurred among women who underwent a low-, intermediate-, and high-risk principal procedure, respectively. Women with SLE who underwent a low-risk principal procedure were significantly more likely to have a composite CVD outcome as compared to women without SLE (311 [2.34%] versus 56,974 [1.57%]; P = 0.003), whereas the difference in composite CVD events among women who underwent an intermediate-risk principal procedure was not significant (20 [0.31%] versus 5,812 [0.39%]; P = 0.66). There were no composite CVD events among women with SLE who underwent a high-risk principal procedure. After adjusting for potential confounders, women with SLE who underwent a low-risk principal procedure were at an increased risk of a composite CVD event relative to women without SLE (Table 2). A similar pattern of association was not observed among women who underwent an intermediate-risk procedure, and the presence of SLE perfectly predicted the absence of a composite CVD event among women who underwent a high-risk principal procedure.
- Top of page
- SUBJECTS AND METHODS
- AUTHOR CONTRIBUTIONS
The perioperative setting represents a time of heightened risk for adverse events. Given the literature on the association between SLE and CVD, we sought to determine whether women with SLE are at an increased risk for adverse perioperative events using hospital discharge data. Our findings revealed that women with SLE who underwent either a low- or high-risk principal procedure had greater than 1.5-fold odds of all-cause in-hospital mortality. In addition, women with SLE who underwent a low-risk procedure had a 40% greater relative risk of short-term CVD events as compared to women without lupus.
Over several previous decades, studies on the association between SLE and premature CVD morbidity and mortality have been accumulating. Deaths in SLE follow a bimodal pattern, with deaths later in the disease course attributed to atherosclerotic events with coronary events and cerebrovascular diseases accounting for up to 20% and 15% of deaths, respectively [3, 5, 9-11, 14, 24]. In terms of CVD morbidity, the prevalence of clinically significant ischemic heart disease has been estimated to approach 17% [4, 7, 8, 12, 25]. In an analysis of the California Hospital Discharge Database, young women with SLE were reported to be at a more than 8-fold greater risk for myocardial infarction and strokes and were 11 times more likely to have heart failure relative to women without SLE . In another report by Manzi et al comparing the rate of CVD events in women with SLE to women in the Framingham Offspring Study, women with SLE had a greater than 2.5- to 52-fold higher rate of CVD events . It is likely that the increased risk of CVD morbidity and mortality in persons with SLE is due in part to a higher prevalence of traditional CVD risk factors, prothrombotic state, and chronic inflammation [15-17].
Several risk indices have been developed to aid clinicians in the preoperative risk stratification of persons awaiting a noncardiac procedure [27-30]. The components of such risk indices include previously recognized CVD, such as coronary heart disease, CHF, and valvular heart disease, in addition to various CVD risk factors, including age, diabetes mellitus, hypertension, and chronic kidney disease. Given that the likelihood of an adverse perioperative coronary event or cardiac-specific mortality is greatest among persons with known or suspected coronary or atherosclerotic disease, it is of clinical relevance whether the perioperative period could represent a period of increased vulnerability to adverse events for persons with SLE. If so, there would be a need for greater scrutiny during perioperative risk assessment and management. More specifically, persons with SLE would then require a perioperative CVD risk stratification and management similar to other disease states such as diabetes mellitus.
Among women undergoing a low-risk procedure, those with SLE had an increased risk of adverse in-hospital perioperative events, including all-cause mortality and composite CVD events, relative to women without SLE. Because these procedures are considered low risk with respect to CVD complications, patients in this group likely included not only those with very low CVD risk, but also those with unsuspected or subclinical CVD and those with recognized CVD but who were judged to be appropriate candidates for the procedures. Therefore, the comparisons in this subgroup were likely least affected by selection factors. In turn, the relatively unselected nature of this subgroup may have helped uncover the perioperative risks associated with SLE. The risk associated with SLE was present in analyses that adjusted for known CVD and its major risk factors, but we could not adjust for subclinical CVD, which might have been present in a higher proportion of women with SLE and was unmasked by the procedure. A preoperative CVD risk assessment may have detected subclinical disease before the event.
In contrast, we did not find a significantly increased risk of perioperative CVD events or in-hospital mortality in those having intermediate-risk procedures, although the risk of mortality tended to be higher in women with SLE. In contrast to low-risk procedures, procedures in the intermediate-risk category are major surgeries recognized to entail an increased risk of complications, including possible CVD complications. Some of these procedures, including many orthopedic procedures, may be discretionary, and patients at an increased risk of CVD complications may elect not to undergo these procedures. Evidence for selection based on risk profile is seen in the comparison of patients undergoing intermediate-risk procedures and those undergoing low-risk procedures. The overall frequency of composite CVD events in the intermediate-risk procedure group was only 35% of that in the low-risk group, and in-hospital mortality was 25% of that in the low-risk procedure group. Moreover, both women with and without SLE in the intermediate-risk procedure group had a much lower prevalence of CVD and CHF than women in the low-risk procedure group. Selection based on known CVD risk and the discretionary nature of the procedures may have served to mitigate any difference in risk of adverse outcomes associated with SLE. Direct evidence of the extent to which selection was responsible for the results would require additional comparisons with women who had indications for these procedures but who did not have them.
Relatively few patients with SLE had high-risk procedures, which limited our ability to estimate differences in the risk of CVD events. However, the risk of in-hospital mortality was significantly higher among women with SLE in this subgroup. The absolute risk of death was also high in this subgroup, reflecting the high-risk nature of these procedures. The increased risk of death in the absence of an increased risk of composite CVD outcomes suggests that noncardiac causes of death predominated in the patients with SLE. However, part of the difference may also be due to sudden cardiac deaths that, although CV in origin, were not accompanied by or identified with a separate premorbid CVD event. Unfortunately, cause of death information was not available.
Although we studied a large and nationally representative sample and examined outcomes by strata of procedural risk, our study also has several limitations. First, the cross-sectional design has inherent limitations. Second, although we adjusted for the presence of known CVD and its major risk factors, the data did not permit adjustment for the severity of these conditions, which may have differed between the women with SLE and those without SLE. There may also be residual confounding by other comorbid conditions or by procedure-related factors such as duration of the procedure or type of anesthesia, although these factors would not be predicted to differ between patients with and without SLE. Third, diagnoses and procedures were abstracted using ICD-9-CM codes; therefore, one must consider the possibility of coding errors or misclassification. Fourth, women with SLE may not have been referred for elective procedures due to its recognized association with CVD risk, but this seems unlikely because the timeframe for the data predated the majority of published literature regarding SLE and CV risk. Fifth, we could not assess the impact of medications on perioperative adverse events due to lack of medication information in the NIS data set. Sixth, we studied only women, since there were too few men with SLE for meaningful analysis by procedure risk group. Finally, our study was only able to determine the risk of short-term in-hospital adverse events, and due to the lack of long-term followup data, does not address the risk of long-term postoperative adverse CVD or mortality events (i.e., 30 days or 60 days).
In conclusion, in a population of hospitalized women who underwent a noncardiac procedure, we found a significant association between SLE and perioperative composite CVD events and all-cause mortality, particularly among those undergoing low-risk procedures. Our study serves as the initial step in attempting to quantify the significance of the atherosclerotic disease in SLE during the perioperative period. Prospective studies are needed to further elucidate the relationship between SLE and perioperative risk, including cause-specific mortality and long-term postoperative CVD and non-CVD morbidity and mortality, and potential benefits of different perioperative risk assessment strategies.
- Top of page
- SUBJECTS AND METHODS
- AUTHOR CONTRIBUTIONS
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Yazdanyar had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study conception and design. Yazdanyar, Wasko, Scalzi, Kraemer, Ward.
Acquisition of data. Yazdanyar.
Analysis and interpretation of data. Yazdanyar, Wasko, Scalzi, Ward.