Lupus Patients with Nephritis at Greater Risk of Cholesterol Disorders, Cardiovascular Events

Desmond Y H Yap, MD, PhD
Credit: Hong Kong University

­An analysis of nearly 2 dozen studies comparing outcomes between patients with systemic lupus erythematosus (SLE) provides an overview of the additional cardiovascular risk associated with nephritis among these patients.

A meta-analysis of 22 studies including more than 8600 patients with SLE, results suggest presence of lupus nephritis (LN) was associated with an increased likelihood of cardiovascular risk factors, including dyslipidemia, diabetes, and hypertension, as well as a 3-fold increase in incidence of cardiovascular mortality.¹

“Our observations are clinically important because these [cardiovascular disease] risk factors are potentially amenable to treatment and their adequate control can modulate the risk of [cardiovascular] morbidity and mortality,” wrote investigators.¹

According to the Lupus Foundation of America, an estimated 1.5 million in the US and more than 5 million worldwide have some form of lupus, with SLE the most common among these. As a result of research efforts and improved management, the long-term prognosis associated with a diagnosis of SLE has increased in recent decades. With improved life expectancy, cardiovascular disease has emerged as the leading cause of death in patients with SLE.^2,3

With this in mind, a team of investigators led by Desmond YH Yap, MD, PhD, clinical associate professor and honorary consultant at Queen Mary Hospital of The University of Hong Kong, launched the current study to better understand how presence of LN might influence cardiovascular risk factors and complications among patients with SLE. To do so, investigators designed their research endeavor as a systematic review and meta-analysis of studies published on the subject from 1947 through 2022.¹

Using the PubMed, EMBASE, MEDLINE, and Scopus databases, investigators performed a search for observational studies, including cross-sectional, cohort, prospective, and retrospective studies, reporting prevalence of cardiovascular disease and cardiovascular disease risk factors in adult patients with SLE with and without nephritis. Of note, investigators performed 2 meta-analyses as part of the study, including a proportional meta-analysis and a meta-analysis of 2-armed studies.¹

A total of 26,361 studies were identified from the investigators’ initial search. After exclusion of duplicates and further screening, 186 articles underwent full-text review. In total, 58 studies were identified for inclusion, with 22 included in the final meta-analysis of 2-armed studies.¹

These studies encompassed 8675 patients with SLE, including 2295 and 6380 patients with and without LN, respectively. These studies had a female predominance (86.7-100%), and varying range of follow-up (2-11 years). Investigators noted all of these studies were conducted between 1990 and 2020.¹

The primary outcome of interest of the study were differences in the prevalence of myocardial infarction (MI), cerebrovascular events, hypertension, hyperlipidemia, diabetes mellitus, and plaque occurrence in patients with SLE with and without nephritis. Secondary outcomes of interest included differences in systolic and diastolic blood pressure, total cholesterol, LDL-C, HDL-C, and triglycerides.¹

Upon analysis, results suggested patients with SLE with nephritis had significantly greater likelihood of hypertension (Odds Ratio [OR], 4.93; 95% CI, 3.17-7.65; P <.00001, I2=56%), hyperlipidemia (OR, 11.0; 95% CI, 4.20-28.95; P <.00001, I2=0%) and diabetes mellitus (OR, 1.88; 95% CI, 1.09-3.25; P=.02, I2=32%) compared to those without nephritis. Further analysis pointed to a trend toward increased prevalence of MI (OR, 1.35; 95% CI, 0.53-3.45; P=.52, I2=78%) and cerebrovascular accident (OR, 1.64; 95% CI, 0.79-3.39; P=.27, I2=23%) among patients with nephritis relative to general patients with SLE. Additionally, analysis of mortality suggested those with SLE and nephritis (11.7 per 1000 patient-years) experienced a greater incidence of cardiovascular mortality than those with SLE without nephritis (3.6 per 1000 patient-years).¹

Investigators highlighted multiple limitations within their study. These included a relatively low number of studies with cardiovascular data on both patients with and without LN, use of outcomes definitions that were often incomplete, and lack of data on other major adverse cardiovascular events, such as heart failure. Investigators also called attention to inherent limitations associated with study of hard cardiovascular events and mortality, including being prone to survivorship bias.¹

“With better early survival, [cardiovascular] morbidity and mortality have become a growing concern in the long-term management of patients with SLE and LN. Our meta-analysis results showed that the presence of LN in patients with SLE was associated with increased risk of various conventional [cardiovascular] risk factors including [hypertension], dyslipidaemia and [diabetes mellitus], and also elevated odds of [cardiovascular] mortality," investigators wrote.¹

References:

1. _{^{Wong CY, Ma BMY, Zhang D, Cheung W, Chan TM, Yap DYH. Cardiovascular risk factors and complications in patients with systemic lupus erythematosus with and without nephritis: a systematic review and meta-analysis. Lupus Sci Med. 2024;11(1):e001152. Published 2024 Mar 21. doi:10.1136/lupus-2024-001152}}
2. _{^{Yen EY, Shaheen M, Woo JMP, et al. 46-Year Trends in Systemic Lupus Erythematosus Mortality in the United States, 1968 to 2013: A Nationwide Population-Based Study. Ann Intern Med. 2017;167(11):777-785. doi:10.7326/M17-0102}}