Mild renal dysfunction is associated with increased risk of ischemic heart disease disease among healthy adults - The 68th Annual Conference of the Israel Heart Society in association with the Israel Society of Cardiothoracic Surgery

Shmuel Tiosano ^1,2 Alexander Fardman ^1,2 Alon Kaplan ^1,2 Maia Kalstein ^1,2 Yonatan Moshkovits ^1,2 Shlomo Segev ^2,3 Pazit Beckerman ^2,4 Amit Segev ^1,2 Ehud Grossman ^2,5 Elad Maor ^1,2

¹Division of Cardiology, Sheba Medical Center, Israel
²Sackler Faculty of Medicine, Tel-Aviv University, Israel
³Institute for Medical Screening, Sheba Medical Center, Israel
⁴Institute of Nephrology and Hypertension, Sheba Medical Center, Israel
⁵Internal Medicine Wing, Sheba Medical Center, Israel

Introduction: The relationship between ischemic heart disease (IHD) and advanced chronic kidney disease is well established. However, there is a paucity of data regarding the long-term association in between renal function and incidence of IHD.

Methods: We evaluated asymptomatic self-referred adults who participated in a medical screening program. All subjects were free of IHD at baseline. Glomerular Filtration Rate (GFR) was calculated by CKD-EPI and divided into quartiles (Q1 represents the lowest quartile). Study endpoint was the development of IHD which was externally adjudicated by a physician. Cox regression models were applied while adjusting for confounders.

Results: The final study population included 27,647 subjects (68% men) with a mean age of 47 years. At baseline (first screening visit), median GFR by CKD-EPI was 84 [IQR 74;95] and 86 [IQR 74.;101] mL/min per 1.73m² for men women, respectively. During median follow up of 6 years [IQR 2;12], 2,286 (8%) of subjects developed IHD, of whom 1,912 (10%) were men and 374 (4%) were women. Incident IHD was in 964 (13.98%), 705 (10.22%), 437 (6.34%) and 171 (2.48%) subjects from GFR Q1-Q4, respectively. Kaplan Meier survival analysis demonstrated a graded increased risk of IHD with decreasing eGFR quartiles (p Log rank <.001; FIGURE). Multivariate cox regression analysis revealed hazard ratio of 1.26 (95%CI 1.06, 1.51), 1.43 (95%CI 1.20, 1.70), and 1.25 (1.05, 1.50) for IHD incidence for Q1-Q3, respectively (using Q4 as reference). While considering GFR as a continuous variable, each 10 units increase in GFR was significantly associated with 4% less risk for developing IHD - HR 0.96 (95%CI 0.93-1.00, p=0.04).

Conclusion: Mild renal dysfunction even within the normal range is independently associated with remote risk of IHD among young apparently healthy adults. Cardiovascular screening should be considered among young patients with reduced renal function, even within normal reference range.