Proteinuria Linked to Sudden Cardiac Arrest in Young Adults

A familiar biomarker emerged as a potential predictor of sudden cardiac arrest (SCA) in young people, which remained hard to explain even with genetic testing.

Although SCA was rare in a Korean population-based study — occurring in 0.08% of over 6.8 million adults under age 40 — it was more likely in those whose routine lab results flagged proteinuria (adjusted HR 1.71, 95% CI 1.47-1.99) approximately 10 years prior.

The finding persisted whether the patient had shown later-stage proteinuria (adjusted HR 2.94, 95% CI 1.96-4.40) or early-stage proteinuria (adjusted HR 1.61, 95% CI 1.37-1.89), according to Jong-Il Choi, MD, PhD, MHS, MSc, of Korea University College of Medicine and Korea University Anam Hospital in Seoul, and colleagues.

On subgroup analysis, the tie between elevated protein in urine and subsequent SCA was especially strong in those with existing chronic kidney disease stage 3 (adjusted HR 2.81, 95% CI 1.47-5.40) and stages 4-5 (adjusted HR 5.70, 95% CI 3.56-9.12). However, the proteinuria-SCA link was also evident in healthy individuals without established cardiovascular disease (CVD) or risk factors at baseline (adjusted HR 1.44, 95% CI 1.13-1.85), Choi’s group reported in the Journal of the American Heart Association.

“Although the overall incidence of SCA was low in [a] young population, a significant association was observed between the proteinuria in spot urine samples and the risk of SCA. We also observed a dose-dependent relationship, with a higher protein concentration in the urine associated with a higher risk of SCA,” study authors wrote.

For now, SCA remains hard to predict despite developments in genetic testing for presumed pathological variants. The hope is that a surrogate marker like proteinuria — a known sign of kidney disease and an established risk factor for CVD — can identify at-risk individuals.

If this concept pans out with further study, it could make a case for more population-wide screening.

“Proteinuria often reflects systemic endothelial dysfunction or damage to the blood vessels, which is a key feature of CVD manifestation. The endothelial dysfunction associated with proteinuria may lead to SCA even at a young age,” explained So Mi Jemma Cho, PhD, of Massachusetts General Hospital and the Broad Institute in Boston, and Tae-Hyun Yoo, MD, PhD, of Yonsei University College of Medicine in Seoul.

“Through strategic leveraging of the existing surveillance and systematic referral system, longitudinal tracking of renal function may further enhance detection and effectively reduce cardiorenal complications,” the duo suggested in an accompanying editorial.

In Korea, the government provides complimentary biennial screening for adults. Before age 18, spot urine analysis of protein is already widely used for children beginning in primary school.

While the U.S. does include proteinuria screening in primary care, routine urinalysis for children and adolescents is not recommended, Cho and Yoo noted.

“In summary, [the study authors] have provided us with valuable insights that we believe should spur initiation and expansion of upstream proteinuria prevention efforts. We highlight that screening is an expansive, noninvasive, and effective approach to detect proteinuria in a timely manner and to implement appropriate interventions,” they stressed.

The work by Choi’s group included over 6.8 million adults ages 20-39 years who had a health screening in South Korea between 2009 and 2012. Nationwide administrative records provided SCA data, with a mean follow-up of 9.4 years. Mean age was 30.9 years and 59.5% were men.

Those with proteinuria tended to have a higher prevalence of hypertension (16.5% vs 7.3%), diabetes (6.3% vs 1.9%), and dyslipidemia (9.1% vs 5.7%) than peers with no more than trace protein detected in urine.

Choi and colleagues cautioned that inherent to the observational design of the study was the possibility of residual confounding despite statistical adjustments. Additionally, the study lacked 24-hour urine protein or spot urine protein/creatinine ratio data and did not account for follow-up urine protein measurements. Study results may also have limited generalizability to other ethnic groups, they noted.

“With the emergence of a cardio-kidney-metabolic syndrome prevention framework and the inclusion of renal function in the novel [PREVENT] prediction paradigm, the comparative predictive performance of proteinuria should be further explored in demographically and clinically diverse populations to better identify high-risk individuals,” wrote Cho and Yoo.

Please enable JavaScript to view the

comments powered by Disqus.