Sex difference in the risk for exercise-induced albuminuria correlates with hemoglobin A1C and abnormal exercise ECG test findings.

BACKGROUND: Albuminuria is an established marker for endothelial dysfunction and cardiovascular risk in diabetes and prediabetes. Exercise induced albuminuria (EiA) appears earlier and may be a more sensitive biomarker for renal endothelial damage. We sought to examine the association between EiA, parameters of the metabolic syndrome, A1C levels, exercise ECG test results and sex related differences in a large cohort of healthy, pre-diabetic and diabetic subjects. METHODS: A total of 3029 participants from the Tel-Aviv Medical Center Inflammation Survey cohort (mean age 46 years, 73% men) were analyzed. Multiple physiologic and metabolic parameters including A1C were collected and albuminuria was measured in all subjects before and immediately after completing an exercise ECG test. RESULTS: Exercise increased urinary albumin to creatinine ratio (ΔEiA) by 2.8 (0-13.6) mg/g for median (IQR) compared to rest albuminuria (p < 0.001). An increase in ΔEiA was observed with accumulating parameters of the metabolic syndrome. ΔEiA showed significant interaction with sex and A1C levels; i.e. women with A1C > 6.5% had an increased risk of higher ΔEiA (p < 0.001). Using a cutoff of ΔEiA > 13 mg/g (top quartile) we found that women with ΔEiA > 13 mg/g were at greater risk for abnormal exercise ECG findings, (OR = 2.7, p = 0.001). CONCLUSION: Exercise promotes excessive urinary albumin excretion in dysmetabolic patients. In women, a significant correlation exists between ΔEiA and A1C levels. A cutoff of ΔEiA > 13 mg/g in women may be used to identify populations at risk for abnormal exercise ECG test findings and perhaps increased cardiovascular risk. Future studies will be needed to further validate the usefulness of ΔEiA as a biomarker for cardiovascular risk in women with and without diabetes.

The ability of the wide range CRP assay to classify individuals with low grade inflammation into cardiovascular risk groups.

BACKGROUND: High sensitivity C-reactive protein (hsCRP) has become a routine assessment tool to discriminate between patients at low, intermediate or high risk for cardiovascular events using the threshold values of 1 and 3mg/L, respectively. Over the past years, several studies have proposed the wide range C-reactive protein (wrCRP) as an alternative to the hsCRP in various clinical scenarios. However, the potential use of wrCRP in assessing the cardiovascular risk has not yet been evaluated. METHODS: Both wrCRP and hsCRP were evaluated in 15,780 apparently healthy individuals who underwent a routine annual checkup in the Tel Aviv Sourasky Medical Center. Individuals with CRP levels >5mg/L were excluded. Agreement between the two methods was observed using the Bland-Altman method and the concordance correlation coefficient. Deming regression was used to build a calibration equation. Reclassification of individuals' risk level was observed and Cohen's kappa was used to evaluate risk agreement. RESULTS: A high correlation (r=0.98) along with a significant difference (p<0.001) between hsCRP and wrCRP raised the need for calibration. A simple calibration equation (Adjusted wrCRP=0.3136+0.8803×wrCRP) led to high agreement which enabled 8.4% reclassification of the risk group. A change in the intermediate risk threshold value from 1 to 0.9mg/L led to an almost perfect agreement (kappa=0.87, p<0.001) and a low reclassification rate (7.6%), with under 0.05% of the population undergoing a major reclassification (from high to low risk or vice versa). CONCLUSIONS: In the era of limited financial resources, wrCRP assay may be used as a reasonable routine assay to evaluate the cardiovascular risk in patients undergoing a routine annual checkup.