Heart rate variability indices for predicting cardiorenal outcomes: A lesson from the PERL and ACCORD cohorts

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  Figure 1. Illustrates the interrelationships between cardiac autonomic neuropathy (CAN) and diabetic kidney disease (DKD) progression in individuals with diabetes, focusing on mechanisms in type 1 diabetes and type 2 diabetes. CAN, caused by hyperglycemia‐induced metabolic derangements, compensatory hyperinsulinemia due to insulin resistance, inflammation accompanied by adipose tissue dysfunction, and other metabolic factors often associated with metabolic syndrome, is defined by heart rate variability (HRV) measures on an electrocardiogram (ECG). CAN can lead to late manifestations such as resting tachycardia, orthostatic hypotension, syncope, falls, exercise intolerance, prolonged QT interval, and cardiac arrhythmia. Sympathetic activation in the heart and kidneys, driven by CAN, may lead to increased activation of the renin‐angiotensin‐aldosterone system (RAAS), a non‐dipping blood pressure (BP) profile, and increased inflammation. These mechanisms result in cardiovascular disease (CVD), heart failure (HF), silent myocardial ischemia, and sudden cardiac death. In the kidneys, sympathetic activation can also lead to intraglomerular hypertension and hyperfiltration, contributing to rapid…