Fasting Glucose Levels Within the High Normal Range Predict Cardiovascular Outcome

Kivity Shaye, MD; Tirosh Amir, MD, PhD; Segev Shlomo, MD; Sidi Yechezkel,MD

Disclosures

Am Heart J. 2012;164(1):111-116. 

In This Article

Results

Data from 10,913 apparently healthy men and woman (mean age 50.4 years, range 34–91), 9,687 with FPG levels of < 100 mg/dL at baseline and 1,226 with IFG values (100–125 mg/dL), were analyzed. Participants were categorized based on glucose levels to 5 groups (50–79, 80–84, 85–89, 90–94, and 95–99 mg/dL). In addition, we have also analyzed the IFG group (100–125 mg/dL). Age, male gender, systolic blood pressure, family history of CVD, TG, and LDL cholesterol levels were more likely to increase across the entire range of fasting glucose level. The percentage of current smokers and HDL cholesterol levels inversely correlated with FPG levels Table I).

During 46,991 person-years of follow-up (mean follow-up, 4.3 years), there were 1,119 documented incident cases of CVD end-points. Age-adjusted HRs for CVD outcomes have increased linearly across the entire range of FPG levels, with significant HR already observed for FPG levels of 85 to 89 mg/dL (1.34, 95% CI 1.08–1.65), reaching an HR of 1.53 (95% CI 1.2–1.9) for the 95-to-99-mg/dL group as compared with the lower FPG group (P for trend <.001) (Table II).

In a multivariate model adjusted for age, sex, BMI, systolic blood pressure, TGs, HDL and LDL-cholesterol levels, smoking status, pharmacologic treatment, and family history for CHD, we observed a significant and progressive increase in the risk of CVD events in individuals with FPG levels in the third, fourth, and fifth groups as compared with the low-glucose group (P for trend <.001) (Table II). The addition of the IFG group (100–125 mg/dL) further improved the prediction model (P < .001 on the basis of the likelihood-ratio test). In a multivariate model adjusted for the above parameters using FPG levels in the normoglycemic range as a continuous variable, we revealed a significant increase of 7.6% in the risk for CVD for every increment of 1 mg/dL of glucose. In a subgroup analysis, we excluded patients who had developed DM before having a cardiovascular event. The risk for CVD remained significant even after multivariant analysis controlling for the aforementioned risk factors. We further analyzed the interaction of sex and FPG in respect to cardiovascular risk, which was nonsignificant (P of interaction = .321).

When stratified for the various component of the composite CVD outcome, increased FPG in the normoglycemic range was associated with increased risk of coronary but not of cerebrovascular events, for which the risk had increased significantly only for the IFG group (Table III). To better assess whether the correlation between FPG and CVD is age related, we next stratified the study population based on the mean age of 50 years. Although both groups showed similar correlations between FPG levels and CVD outcomes, only the group of participants older than 50 years (n = 5072) had reached statistically significant HRs (P < .05 for all groups as compared with the reference group). The P value for interaction between FPG, age, and CVD outcomes was insignificant (P = .478). The importance of each risk factor for CVD was ranked independently by the Wald score: for FPG levels the score was 15.3, after age (171), gender (39) and smoking (17.9) similar to hypertension (15.2) and more significant than BMI (3.6), family history (10.6), cholesterol (12.4), and TG (7.2). We next assessed mortality rates at each FPG group. Mortality rates were not statistically different for groups 1 though 5 being 2.3, 2.1, 2.1, 2.3, and 3.3 per 1000 participants per year, respectively (P = .25). Mortality among participants of the IFG group was higher, reaching 5.7 per 1000 participants per year (P = .016).

To confirm previous observations that increased FPG in the normal range is associated with incident DM in young adults could also be observed in an older population, we next analyzed the cases of new-onset DM based on FPG at baseline. During the follow-up period, 22% of those in the IFG compared with only 0.2% of those in the lowest FPG group developed DM. After adjustment for age, sex, BMI, hypertension, TGs, LDL, HDL, smoking status, and family history for DM, the HR for the IFG group was 77 (95% CI 32–186), as compared with 18 (95% CI 7.5–46) in the 95-to-99-mg/dL group and with 3.9 (95% CI 1.48–10.36) observed for those with FPG of 80 to 84 mg/dL.

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