Baseline characteristics
The entire prospective cohort included 11,374 participants from the Northern provinces of Iran. Among the cohort 1,543 had DM at baseline and were excluded from this analysis. Among the remaining 9,831 participants, 2,410 (24.5%) had IFG, and 7,421 (75.5%) had normal fasting glucose (NFG), and they were included in this analysis.
Baseline characteristics of the study population are demonstrated in Table 1. The prevalence of HTN (44.2 vs. 34.7%; p, 0.000) and DLP (49.9 vs. 39.7%; p, 0.000) were significantly higher in IFG population compared to the normoglycemic group. Moreover, compared to NFG group, the IFG group were older and had a significantly higher level of BMI, waist circumference (WC), SBP, DBP, TG, cholesterol, and low density lipoprotein (LDL) (p=0.000, all). Participants with IFG were more likely to use a statin medication than did the NFG group (3.7 vs. 2.7%; p, 0.007). However, sex difference (47.3 vs. 48.4%; p, 0.3), smoking status (8.1 vs. 9.2%; p, 0.08), and HDL level (61.4 vs. 61.2; p, 0.7) were not significantly different between the two groups.
IFG and CVD outcomes
Over a mean follow up of 6.2 (± 0.1) years, 297 MACE (199 CVD deaths, 43 non-fatal MI, and 55 non-fatal strokes) were reported. CVD death comprised of 108 fatal MI, 74 fatal strokes, and 17 deaths due to heart failure.
Table 2 shows HRs and 95% CI of MACE according to glycemic status, HTN, and DLP. The occurrence of MACE was not significantly different between those with IFG but without HTN or DLP compared to NFG participants who also did not have HTN or DLP (fully adjusted HR, 1.05; 95% CI, 0.59-1.86; p, 0.8). However, presence of both HTN and DLP with IFG was associated with significantly higher hazard of MACE compared to the reference group (fully adjusted HR, 2.85; 95% CI, 1.79-4.54; p, 0.000). The presence of HTN+DLP in normoglycemic participants confers a considerable hazard for MACE (fully adjusted HR, 2.58; 95% CI, 1.72-3.87; P, 0.000), however, it is somewhat less than hazard of MACE imposed by HTN+ DLP in individuals with IFG. When participants were categorized based on glycemic status with the presence or absence of HTN alone, individuals with IFG plus HTN showed significantly higher hazard of MACE compared to those with NFG and without HTN (fully adjusted HR, 2.75; 95% CI, 1.93-3.90; p, 0.000). However, IFG without HTN did not increase the hazard of MACE compared to NFG without HTN (fully adjusted HR, 1.19; 95% CI, 0.77-1.84; p, 0.4). The presence of HTN in normoglycemic participants was associated with significantly higher HR of MACE compared to the reference group (fully adjusted HR, 2.57; 95% CI, 1.92-3.43; P, 0.000). HRs for MACE was also evaluated according to glycemic status in the presence or absence of DLP. Compared to the reference group, IFG with DLP did not increase the hazard of MACE (fully adjusted HR, 1.24; 95% CI, 0.88-1.77; p, 0.2).
Kaplan-Meier analysis with log- rank test shows that addition of IFG to HTN, DLP, or both did not decrease MACE free survival (Figure 1; p > 0.05 for all comparisons).
We next examined the effect of IFG with HTN, DLP, or both HTN + DLP on the occurrence of individual components of MACE in greater detail. Table 3 shows the effect of IFG in the presence of HTN+DLP on the occurrence of the individual components of MACE. IFG plus both HTN and DLP was associated with a significant increase in the hazard of fatal MI (fully adjusted HR, 2.74; 95% CI, 1.20-6.21; p, 0.01). However, IFG in the absence of neither HTN nor DLP did not increase the hazard of fatal MI (fully adjusted HR, 1.20; 95% CI, 0.47- 3.01; P, 0.6). The combination of IFG with both HTN and DLP did not increase the risk of non-fatal MI (fully adjusted HR, 1.12; 95% CI, 0.23-5.46; p, 0.9) compared with NFG in the absence of HTN+DLP. Considerably, IFG in the presence of both HTN and DLP conferred a significantly higher hazard (fully adjusted) of both fatal stroke (HR, 5.13; 95% CI, 2.08-12.63; p, 0.000) and non-fatal stroke (HR, 2.52; 95% CI, 1.06-6.02; p, 0.04), compared to NFG in the absence of HTN+DLP. However, IFG in the absence of either HTN or DLP was not associated with increased hazard of fatal (fully adjusted HR, 1.37; 95%CI, 0.43-4.40; p, 0.6) or non-fatal stroke (fully adjusted HR, 0.52; 95%CI, 0.12-2.30; p, 0.4).
The results indicated that IFG in the presence of HTN is associated with a significantly higher hazard of fatal MI (fully adjusted HR, 2.66; 95% CI, 1.48-24.78; p, 0.001) but not non-fatal MI ( fully adjusted HR, 1.57; 95% CI, 0.56- 4.46; p, 0.4) compared to NFG in the absence of HTN (Table 4). IFG plus HTN was associated with the higher hazard of both fatal (fully adjusted HR, 3.72; 95% CI, 1.84-7.55; p, 0.000) and non-fatal (fully adjusted HR, 2.34; 95% CI, 1.18-4.62; p, 0.01) stroke. However, IFG in the absence of HTN did not increase the hazard of any of the above cardiovascular events (Table 4).
IFG in the presence of DLP, compared to NFG in the absence of DLP, was associated with an increased risk of fatal stroke both in unadjusted model (HR, 2.17; 95% CI, 1.22-3.88; p, 0.009) and in adjusted models number 1(HR, 2.40; 95% CI, 1.33-4.31; p, 0.003) and number 2 (HR, 2.47; 95% CI, 1.34-4.53; p, 0.004). However, IFG in the presence of DLP did not increase the risk of fatal MI (fully adjusted HR, 1.50; 95% CI, 0.84-2.70; p, 0.2), non-fatal MI (fully adjusted HR, 0.72; 95% CI, 0.21-2.52; p, 0.6), and non-fatal stroke (fully adjusted HR, 1.31; 95% CI, 0.66-2.58; p, 0.4). Likewise, IFG in the absence of DLP did not increase the hazard of any of the above cardiovascular events (Table 5).