Rates of Cardiovascular Events in Patients With Glomerular Disease

Patients with all-cause chronic kidney disease (CKD) are at high risk for cardiovascular events. As estimated glomerular filtration rate (eGFR) decreases below 60 mL/min/1.73 m², the risk of cardiovascular disease increases exponentially. There is an association between levels of proteinuria <150 mg/d and a doubling of cardiovascular risk.

According to Mark Canney, MD, PhD, and colleagues, there are few data available on the risk of cardiovascular disease in patients with various primary glomerular diseases. The absolute risk of cardiovascular disease from the time of diagnosis in patients with each type of primary glomerular disease is unknown, limiting the clinical implementation of cardiovascular prevention strategies in patients who may be younger and retain kidney function and may not be recognized as being at high cardiovascular risk.

The researchers conducted an observational cohort study in a population-level cohort of adults with primary glomerular disease to describe the risk of cardiovascular disease compared with the general population and the impact of traditional and kidney-related risk factors on cardiovascular risk. Results were reported in the American Journal of Kidney Diseases [2022;80(6):740-750].

Study exposures were traditional cardiovascular disease risk factors (diabetes, age, sex, dyslipidemia, hypertension, smoking, prior cardiovascualr disease) and kidney -related risk factors (type of glomerular disease, eGFR, proteinuria). The primary outcome of interest was the occurrence of any major adverse cardiovascular event or any revascularization procedure after biopsy. The composite outcome included coronary artery, cerebrovascular, and peripheral vascular events, and death due to myocardial infarction or stroke.

Subdistribution hazards models were used to evaluate the outcome risk with noncardiovascular disease death treated as a competing event. Standardized incidence rates (SIRs) were calculated based on the age- and sex-matched general population.

The cohort included 1912 adults in British Columbia, Canada, with biopsy-proven membranous nephropathy (n=387), minimal change disease (MCD) (n=226), IgA nephropathy (IgAN) (n=759), or focal segmental glomerulosclerosis (FSGS) (n=540). Eligible participants were diagnosed between January 1, 2000, and December 31, 2012. Mean age of the total cohort was 50.6 years, 59.5% (n=1127) were male, and median duration of follow-up was 6.8 years.

During the median 6.8 years of follow-up, 11.1% (n=212) patients experienced the primary cardiovascular disease outcome: 6.0% (n=115) with a coronary artery event; 2.4% (n=46) with a cerebrovascular event; and 2.7% (n=51) with a peripheral vascular event (individual cardiovascular events were mutually exclusive).

In the overall cohort, the 10-year risk of experiencing a cardiovascular event was high: 14.7%; (95% CI, 12.8%-16.8%). There were significant differences in risk across types of glomerular disease. The risk was highest in patients with FSGS and membranous nephropathy and lower in those with IgAN and MCD (Gray test P<.001). Nonetheless, the absolute 10-year risk was high in each type of glomerular disease: 7.4% (95% CI, 5.2%-10.0%) in IgAN; 12.1% (95% CI, 7.0%-18.8%) in MCD; 17.6% (95% CI, 13.1%-22.7%) in membranous nephropathy; and 23.7% (95% CI, 19.3%-28.3%) in FSGS.

Using the Kidney Disease Improving Global Outcomes guideline recommendations that consider a crude incidence of 10 cardiovascular events per 1000 person-years as a threshold beyond which cardiovascular risk is high, the incidence of cardiovascular events was high for the overall cohort (24.7 per 1000 person-years; 95% CI, 22.2-27.4), as well as for each individual type of glomerular disease. Patients with FSGS and membranous nephropathy had higher incidence of cardiovascular events compared with those with IgAN. In the total cohort, the incidence was similar during each year of follow-up following biopsy.

The incidence of cardiovascular events was age- and sex-specific standardized to the general adult population in British Columbia. For the overall cohort, the SIR was 2.46 (95% CI, 2.12-2.82), indicating that the rate of cardiovascular events was 2.5 times that of the general population. There was also greater risk compared with the general population for each individual type of glomerular disease: for FSGS, 3.98 (95% CI, 3.19-4.91); for membranous nephropathy, 3.03; (95% CI, 2.23-4.03); for MCD, 1.76 (95% CI, 1.03-2.82); and for IgAN, 1.38 (95% CI, 1.01-1.85).

There were individual associations between the traditional cardiovascular risk factors (age, male sex, hypertension, diabetes, dyslipidemia, smoking, and prior cardiovascular event) and a higher risk of cardiovascular events. In unadjusted analyses, there was an association of each doubling of proteinuria at biopsy and a 30% greater cardiovascular risk (subdistribution hazard ratio [SHR], 1.3; 95% CI, 1.2-1.5; P<.001). There was an association between lower eGFR at biopsy and greater risk; the association was seen even in those with eGFR between 60 and 90 mL/min/1.73 m² (SHR, 1.9; 95% CI, 1.1-3.3; P=.03).

Compared with patients with IgAN, the risk of cardiovascular events was significantly higher in those with FSGS (SHR, 3.4; 95% CI, 2.4-4.8; P<.001) and membranous nephropathy (SHR, 2.4; 95% CI, 1.6-3.6; P<.001). There was no significant increase in risk among those with MCD (SHR, 1.3; 95% CI, 0.8-2.3; P=.3).

The researchers cited some limitations to the study findings including the potential for misclassification of glomerular disease, the possibility of unmeasured confounding, utilizing hospital data for the primary outcome, and using administrative definitions of comorbid conditions.

In conclusion, the authors said, “Our findings provide convincing evidence that individuals with biopsy-proven IgAN, membranous nephropathy, MCD, and FSGS have a high risk of experiencing cardiovascular events that is approximately 2.5 times that of the general population. This risk differs by type of glomerular disease and is present both before and after the onset of kidney failure. Cardiovascular risk stratification may be improved by considering glomerular disease-specific risk factors in addition to traditional cardiovascular risk factors. Further research is warranted to better understand the mechanisms underlying this heightened risk of cardiovascular disease so that we can potentially intervene early and improve cardiovascular outcomes for patients with glomerular disease.”

Takeaway Points

1. Researchers reported results of an observational cohort study designed to examine the risk of cardiovascular disease in adults with glomerular disease compared with the general population.
2. For the overall cohort, the incidence rate of cardiovascular events was high at 24.7 per 1000 person-years and for each disease type (range, 1.22-46.1 per 1000 person-years).
3. The incidence rate of cardiovascular events was higher among the patients with glomerular disease than among the general population of British Columbia, Canada.