The gender-specific role of prediabetes on 10-year cardiovascular disease incidence: highlights from the ATTICA prospective (2002–2012) study
Authors: Kouvari M , Panagiotakos D.B , Chrysohoou C , Georgousopoulou E.N , Pitsavos C , Tousoulis D 
Published: November 2020

Abstract

Background/Introduction
Prediabetes in terms of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) are highly discussed for their aggravating effect on cardiac health and their potential inclusion in risk prediction to achieve earlier prevention.

Purpose
The aim of the present work was to evaluate the association between prediabetes and 10-year first fatal/non fatal cardiovascular disease (CVD) incidence in a sample without prevalent CVD, taking into account the stability of this condition or the transition to type II diabetes.

Methods
A prospective study was conducted during 2001–2012 studying n=1,514 males and n=1,528 females (aged &gt;18 years old) free of CVD. According to American Diabetes Association Diagnosis, prediabetes in terms of IFG was defined as fasting glucose levels 100–125 mg/dl while type 2 diabetes as fasting blood glucose &gt;125 mg/dl or the use of antidiabetic medication. Ten-year follow-up was performed in n=2,020 participants (n=317 CVD cases); the working sample here was n=1,485 (n=249 CVD cases) (without baseline diabetes and with available data on diabetes status at follow-up).

Results
Of the 1,485 participants, n=279 had IFG, at baseline. Ten-year CVD incidence was 19.3% in IFG subgroup and 12.3% in normoglycemic subgroup (p&lt;0.001); the IFG-to-normoglycemic CVD incidence ratio in men was 1.22 while in women 1.60. Multi-adjusted analysis revealed that IFG was an independent predictor of CVD within the decade (Hazard ratio (HR)=1.39, 95% Confidence Interval (95% CI) (1.00, 1.95)). Significant interacting effect of gender on the examined association was revealed (p for interaction=0.001); in stratified analysis, IFG was independently associated with increased CVD risk only in women (HR=1.47, 95% CI (1.10, 2.68)). Within the decade, transition to diabetes status was observed in about one out of four participants with prediabetes (25.1%) while the respective rate in normoglycemic participants was 10% (n=191 diabetes cases, in total). Interestingly, sensitivity analysis revealed that when this category (with diabetes onset within the decade) was excluded from the analysis prediabetes retained its independent aggravating –even weaker– effect on 10-year CVD risk in total sample (HR=1.18, 95% CI (1.01, 1.91)) as well as in women (HR=1.25, 95% CI (1.03, 2.97)).

Conclusion
Here, it was suggested that IFG independently predicted long-term CVD onset, even without transition to a more serious cardiometabolic condition (i.e. diabetes) with more evident outcomes in case of women. Considering the increasing interest for early CVD risk prediction, prediabetes condition in terms of IFG may be a useful predictor towards this perspective.

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): This work was supported by a research grant from Hellenic Atherosclerosis Society. The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].