BackgroundThe independent prognostic impact of diabetes mellitus (DM) and prediabetes mellitus (pre‐DM) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐DM on survival outcomes in the GISSI‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial.Methods and ResultsWe assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI‐HF trial, who were stratified by presence of DM (n=2852), pre‐DM (n=2013), and non‐DM (n=2070) at baseline. Compared with non‐DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐DM patients and those with pre‐DM. Cox regression analysis showed that DM, but not pre‐DM, was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI, 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI, 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI, 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI, 1.01–1.29, respectively).ConclusionsPresence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.

1. The sodium concentration in lymphocytes was measured in a group of 66 normotensive subjects (40 without familial hypertension and 26 with familial hypertension), in a group of 81 patients with essential hypertension and in a group of 14 patients with secondary hypertension. 2. The mean value (+/- SD) in normotensive subjects with no history of familial hypertension was 21.9 +/- 3.1 mmol/kg wet weight, which was significantly lower (P less than 0.005) than that of normotensive subjects with familial hypertension (mean value 27.9 +/- 4.2 mmol/kg). Lymphocyte sodium concentration was significantly higher in patients with essential hypertension (33.2 +/- 3.3 mmol/kg; P less than 0.001) than in the subjects with normal blood pressure without familial hypertension. 3. In the patients with essential hypertension there was a significant correlation between lymphocyte sodium concentration and systolic (P less than 0.005), diastolic (P less than 0.001) and mean (P less than 0.001) blood pressure. In the normotensive subjects there was no correlation between the lymphocyte sodium concentration and the blood pressure. 4. The patients with secondary forms of hypertension had normal lymphocyte sodium concentration, except in the case of Conn's disease. 5. Incubation with ouabain increased lymphocyte sodium concentration in the normotensive subjects and patients with essential hypertension; the final sodium concentration was similar in the two groups. 6. When lymphocytes from normotensive subjects without familial hypertension were incubated in plasma of patients with essential hypertension there was an increase in their sodium content.

1. Intralymphocytic sodium concentration was measured in 50 patients with essential stable hypertension, 44 patients with labile hypertension and 40 subjects with normal blood pressure. 2. Intralymphocytic sodium concentration in normotensive subjects was significantly lower than in the other two groups. 3. The concentration was significantly correlated with mean blood pressure in the group as a whole and in the groups with stable and with labile hypertension. No correlation was found in normal subjects.

In subjects with borderline (BL) hypertension and in normal subjects with familial hypertension (FH), the increase in diastolic blood pressure (DBP) induced by mental arithmetic, handgrip and bicycle exercise strongly correlates with intralymphocytic sodium concentration (ILSC). In BL subjects with high or normal ILSC basal BP values are identical, but the increase in DBP during stress is significantly greater in BL subjects with high ILSC. The same phenomenon can be found in normal subjects with FH. Four hours after acute salt loading urinary Na+ is significantly higher in BL subjects with high ILSC. ILSC is a test by which one can identify BL and normal subjects with abnormal responsiveness to stimuli and who probably are fated to develop sustained hypertension.

Thirty patients (26 men, 4 women, mean age 61 +/- 8 years) who had suffered myocardial infarction 15 +/- 6 months previously, were submitted to (1) standard stress-redistribution thallium-201 single photon emission tomography (SPET), (2) rest-redistribution 201T1 SPET and (3) stress-rest technetium-99m sestamibi SPET. Uptake modifications in relation to exercise-induced defects were evaluated in a total of 390 myocardial segments. Tracer uptake was scored as normal (=0), mildly reduced (=1), apparently reduced (=2), severely reduced (=3) or absent (=4). Comparison of stress studies failed to show any statistical difference (58% segmental abnormalities with sestamibi vs 61% with thallium). Uptake abnormalities (score 1-4) were detected in 55% of the segments with sestamibi, 55% with standard thallium redistribution, 55% with early imaging after thallium injection at rest and 54% with 3-h delayed rest imaging (P = NS). Absence of tracer uptake (score = 4) under resting conditions was recorded in 75 (19%) segments with standard 201T1 redistribution, 75 (19%) with rest sestamibi, 70 (18%) with rest 201T1 imaging and 62 (16%) with rst-redistribuion 201T1 (P < 0.05 vs other imaging modalities). Thus, 3-h delayed rest thallium imaging detected reversibility of uptake defects in a significantly higher number of myocardial segments. This finding might have important implications for both tracer and technique selection when myocardial viability is the main clinical issue.