Cardiovascular Risks Persist in Lupus


Patients with systemic lupus erythematosus (SLE) remain at high risk for cardiovascular (CV) disease, Swedish researchers reported.

Among a long-term cohort of patients with SLE, the incidence rate ratio (IRR) for acute myocardial infarction (MI) was 3 (95% CI 1.3-6.9, P<0.001), according to Ola Nived, MD, and colleagues from Lund University.

An elevated IRR also was seen for ischemic cerebrovascular events (2.1, 95% CI 1.5-2.8, P<0.001), the team reported online in Lupus Science & Medicine.

Earlier research in the 1970s identified a bimodal pattern of morbidity and mortality among SLE patients, with active disease and infections predominating early in the course of disease and disease damage and CV disease increasing in importance after lengthy disease duration.

“With better understanding of the disease mechanisms and more judicious use of different therapeutic modalities, these patterns of manifestations might have changed as some reports indicate,” the researchers wrote.

To investigate this, they analyzed IRRs for specific outcomes within a defined, local catchment area surrounding the city of Lund. This included SLE patients diagnosed from 1981 to 2006, with follow-up through 2016. This portion of the analysis included 175 patients and a comparator population of 196,259 adults.

The second part of the analysis looked at risk factors in a larger SLE cohort that included the Lund patients along with others not limited to the environs of the city. This larger SLE sample included 262 patients.

In that total cohort, 86% were women and mean age was 43.4. Ever smoking was reported by 60% of the patients, hypertension by 15%, and a single patient had diabetes.

In the local catchment group of 175 patients, 85% were women, mean age was 48.3, and the mean annual prevalence of SLE was 59 cases per 100,000. Total follow-up time was 5,560 patient-years.

Of the total 37 MI cases reported, 16 were from the defined Lund group and were used for the calculation of IRRs for the years 1998 to 2016. Of the 44 cerebrovascular events reported, 21 were from the defined Lund cohort and were included in the rate calculations. Both types of events occurred in 10 patients, with six in the Lund group.

The highest IRR for MI was for women younger than 40 (IRR 175, 95% CI 74.8-409, P<0.001), but was also increased in those 40 to 59 (IRR 5.8, 95% CI 1.1-39.5, P<0.01). Among men, the only increase was for those ages 40 to 59 (IRR 7.7, 95% CI 1.5-39.9, P<0.001).

Among patients diagnosed with SLE before age 60, the median disease duration until MI was 20 years compared with 4 years for those older than 60 (P<0.01).

For ischemic cerebrovascular events, women and men of all ages had increased risks, with IRRs of 3.3 (95% CI 2.4-4.6, P<0.001) for women and 3.1 (95% CI 1.8-5.2, P<0.05) for men.

Among women with SLE the IRRs for cerebrovascular events were 11.6 (95% CI 2-6.1, P<0.001) at ages 40 to 59 and 1.5 (95% CI 1.1-2, P<0.05) for ages 60 and older. No increases according to age were observed among men.

Most cerebrovascular events occurred within 10 years of SLE diagnosis, the researchers reported.

In the risk factor multivariable regression analysis (262 patients), sex and hypertension were associated with both MI and cerebrovascular events. Smoking was associated only with MI, but data on smoking were missing for many patients earlier in the study, the team noted.

Although hypertension was more common for both MI and cerebrovascular events, for MI the risk appeared to occur only among patients whose SLE was diagnosed before age 55 — which “stresses the importance of blood pressure measurement in the clinical examination of younger patients with SLE,” the authors wrote.

The mean time to one of these events was 4.8 years among SLE patients with hypertension compared with 12.4 years among those whose blood pressure was normal (P<0.01).

Another factor associated with increased risk for both types of events was a higher disease damage score. In addition, a lower glomerular filtration rate (below 50 mL/min) was linked with acute MI — possibly because of renal damage resulting from active disease, the researchers speculated.

The presence of immunoglobulin G anticardiolipin antibodies was associated with ischemic cerebrovascular events, which was not a surprising finding, the authors added, as they had noted this association in a study published almost 30 years ago.

The new findings confirmed that CV events are common in SLE patients, and “that preventive measures from [the time of] diagnosis should include good control of blood pressure, smoking cessation, and, in addition to controlling disease activity, therapy adjustments to reduce the damage rate,” Nived and colleagues concluded.

Study limitations, they said, included changes in diagnostic techniques over the duration and inadequate information about certain known risk factors.


The study was supported by the Swedish Research Council, the Alfred Osterlund Foundation, the Anna-Greta Crafoord Foundation, the Greta and Johan Kock Foundation, the King Gustav V 80th Birthday Foundation, Lund University Hospital, the Swedish Rheumatism Association, the Medical Faculty of Lund University, the Icelandic Society of Rheumatologist Science Fund, and the Landspitali University Hospital Science Fund.

Nived and co-authors reported no conflicts of interest.

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