Cardiorenal interaction in type 2 diabetes: asymptomatic or symptomatic adverse cardiac remodeling associates with declining renal function
L L Sumbu, J J P Yeo, J Chunggat, P Jerampang, M Mustapha, L M Hamden, Y Y Y Yeo, S T Bumphray, F G Chong, D B Enggong, M Igo, M N A Sulaiman, R H C Jong, A Y Y Fong, D H P FooAbstract
Background
Type 2 diabetes (T2DM) is closely associated with cardiovascular and kidney disease, typically coexisting as a cardiorenal metabolic syndrome (CRM). Heart failure with preserved ejection fraction (HFpEF) is a well-recognised clinical manifestation of CRM. Subclinical detection of HFpEF in patients with T2DM is crucial, as it could lead to a more aggressive multisystem intervention plan, thereby improving clinical outcomes.
Purpose
To evaluate the association between varying cardiac involvement and renal function progression in T2DM patients, and identify contributing modifiers.
Methods
We conducted a baseline cross-sectional analysis of an ongoing multicenter prospective cohort study of T2DM patients aged ≥40 years and ejection fraction (EF) ≥50% from primary and tertiary care settings. Clinical, laboratory, echocardiographic, and biomarker data were collected. Patients were stratified into: A - Control (normal cardiac function); B - Asymptomatic LV Remodeling (elevated LV mass index, left atrial volume index, LV end-diastolic volume index, and/or LV end-diastolic systolic volume index, and/or presence of LV diastolic dysfunction, and/or raised NT-proBNP ≥125pg/ml); and C - Symptomatic LV Remodeling (B criteria + HF symptoms). Associations between cardiac groups and renal function (eGFR) were assessed using comparative statistics and logistics regression.
Results
Of 376 T2DM patients, 216 (Group A) had normal cardiac function (mean age 67 years, 49.5% female), 134 (Group B) had asymptomatic LV remodeling (mean age 70 years, 60.4% female), and 26 (Group C) had symptomatic LV remodeling (mean age 69 years, 34.6% female). All groups showed high burden of hypertension and dyslipidemia (>98%), and mean BMI >26kg/m2. Prevalence of coronary artery disease [CAD (p<0.001)], stroke (p=0.002), and atrial fibrillation [AF (p<0.015)] significantly increased; log NT-proBNP (p<0.001), log hs-TnT (p<0.001), and log GDF-15 (p<0.001) significantly increased; while eGFR (p=0.003) significantly decreased across groups A to C. Groups B (OR=5.2, 95%CI: 2.1 to 13.3, p=0.001) and C (OR=22, 95%CI: 6.6 to 73.1, p<0.001) were significantly associated with eGFR <60mL/min/1.73m2 and hs-TnT >14pg/ml in unadjusted analysis; these associations persisted after adjustment for BMI, waist circumference, duration of T2D and dyslipidemia, history of stroke, CAD, and AF, uncontrolled blood pressure and LDL>1.8mmol/L (Group B: OR=4.4, 95% CI: 1.6 to 11.8, p=0.004; Group C: OR=75.6, 95% CI: 10.2 to 562.2, p<0.001).
Conclusion(s)
Our findings showed a graded association between progressive LV remodeling and declining renal function in T2DM patients with preserved EF. Adjusted associations, including hs-TnT >14 pg/mL, highlight early cardiorenal interactions, supporting routine echocardiographic screening for timely intervention.