Long-term prognostic impact of fasting plasma glucose and myocardial flow reserve beyond other risk factors and heart disease phenotypes
Authors: Caselli C , Filidei E , Menichetti L , Poli M , Petroni D , Guiducci L , Sorace O , Pisani P , Pardini S , Bonora D , Giorgetti A , Gimelli A , Neglia D 
Published: October 2024

Abstract

Background
Cardiometabolic risk factors, including high fasting plasma glucose (hFPG), are emerging determinants of residual mortality risk in patients with coronary artery disease (CAD) or heart failure (HF). Coronary microvascular dysfunction, encompassing a broad spectrum of traditional and emerging risk factors, might be a comprehensive risk predictor in these patients.

Purpose
To assess whether hFPG and global myocardial blood flow (MBF) reserve measured by positron emission tomography (PET), expressing global coronary function, may predict long-term prognosis beyond other risk factors and the presence of obstructive CAD or left ventricular (LV) dysfunction associated with HF.

Methods
Among 281 consecutive patients undergoing cardiac PET/CT because of stable chest pain or dyspnea we retrospectively collected long-term follow-up data in 103 patients (mean age 61±10 years, 74 males) in whom MBF measurements, coronary angiography and clinical data were available. Disease phenotypes included obstructive CAD (35%), LV dysfunction without obstructive CAD (43%) or none (22%).

Results
The mean age was 61±10 years (74 males, 72%). Among CVD risk factors, high LDL-cholesterol (hypercholesterolemia under treatment or LDL-C&gt; 130 mg/dL) was present in 72%, high systemic blood pressure (hypertension under treatment or SBP&gt;130/85 mmHg) in 51%, smoking habits in 49%, obesity (BMI&gt;30 Kg/m2) in 22%, type 2 diabetes under treatment in 17%, low HDL-cholesterol (HDL-C&lt; 40 mg/dL in males and &lt;50 mg/dL in females) in 51%, high triglycerides (TG&gt;150 mg/dL) in 27% and high fasting plasma glucose (FPG&gt;100 mg/dL) in 33%. Global MBF reserve was &lt;2 in 68% of patients. In a median follow-up of 10.9 years (7.8-13.9 IQR), 39 patients (37.8%) died (13.6% cardiac death).
At multivariable Cox analyses including all risk factors and MBF reserve, age (HR 1.06, 95% CI 1.02-1.11), high FPG (HR 2.28, 95% CI 1.09-4.79) and depressed MBF reserve (HR 4.79, 95% CI 2.14-10.69) were the only independent predictors of death (Global χ2 36.74, P=0.0001). When disease phenotypes were added to the model, age (HR 1.07, 95% CI 1.02-1.12), high FPG (HR 2.18, 95% CI 1.02-4.63) and depressed MBF reserve (HR 4.47, 95% CI 1.96-10.18) remained independent predictors of death (Global χ2 37.41, P=0.0004) (Figure 1).
Figure 2 plots the observed all cause death rate in patients with different disease phenotypes stratified for absence/presence of high FPG or MBF reserve &lt;2. Death rate progressively increases according to disease phenotypes and is significantly associated with high FPG (P=0.049) or impaired MBF reserve (P=0.012) in each patient group.

Conclusions
These results suggest a strong long-term prognostic role of high FPG and depressed MBF reserve in a selected high-risk population of patients with high prevalence of obstructive CAD or HF.Figure 1 Figure 2