Masayuki Yamaji

Prognostic role of highly sensitive cardiac troponin I in patients with systolic heart failure

BACKGROUND Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are useful biomarkers in patients with chronic heart failure (CHF). However, the clinical use has limitations due to the low sensitivity of a conventional commercial assay system. Recently, a high sensitive-cTnI (hs-cTnI) commercial assay has become available. METHODS To compare the prognostic value of cTnT and hs-cTnI, we measured hemodynamic parameters and serum levels of cTnT, hs-cTnI and N-terminal pro-brain natriuretic peptide (NT-proBNP)in 258 consecutive CHF patients and then followed these patients for a mean period of 2.6 years. In both assays of cTnT and hs-cTnI, the lowest concentration at which the coeffi cient of variation was < or =10% were 0.03 ng/mL, respectively. Therefore, in the present study, an elevated cTnT or cTnI test was defined as a level of > or =0.03 ng/mL. RESULTS During long-term follow up, there were 20 cardiac deaths. In 258 CHF patients, serum cTnT were elevated (> or =0.03 ng/mL) in 32 patients (12%) and serum hs-cTnI was elevated (> or =0.03 ng/mL) in 112 patients (43%). On stepwise multivariate analyses, high plasma NT-proBNP (> or =627 pg/mL, P = .0063) and hs-cTnI (> or =0.03 ng/mL) (P = .016) were independent significant prognostic predictors but cTnT (> or =0.03 ng/mL) was not. The hazard ratio for mortality of patients with high plasma NT-proBNP (> or =627 pg/mL) and hs-cTnI (> or =0.03 ng/mL) was 5.74 (95% CI, 2.33-14.28, P < .0001) compared to that of those with low NT-proBNP (<627 pg/mL) or hs-cTnI (<0.03 ng/mL). CONCLUSIONS These findings indicate that a high plasma concentration of hs-cTnI is an independent and useful prognostic predictor in patients with CHF.

Effect of eplerenone versus spironolactone on cortisol and hemoglobin A1c levels in patients with chronic heart failure

BACKGROUND It has been reported that mineralocorticoid receptor antagonist improves the prognosis of chronic heart failure (CHF). Recently, hemoglobin A₁(c) (HbA₁(c)) levels have been reported to be an independent risk factor for mortality in CHF, suggesting the important role of insulin resistance in CHF. We compared the metabolic effect of a selective mineralocorticoid receptor blocker eplerenone with spironolactone in CHF patients. METHODS One hundred seven stable outpatients with mild CHF, who were already receiving standard therapy for CHF, were randomized (1:2) to spironolactone (25 mg/d) or eplerenone (50 mg/d). Plasma levels of B-type natriuretic peptide, adiponectin, HbA₁(c) and cortisol were measured before and after 4 months treatment with spironolactone or eplerenone. RESULTS There were no differences in baseline characteristics including hemodynamic parameters and plasma levels of biomarkers between 2 groups. In both groups, plasma B-type natriuretic peptide levels were significantly decreased and plasma aldosterone levels were significantly increased after 4 months. In patients receiving spironolactone (n = 34), plasma adiponectin levels were significantly decreased (12.6 ± 1.4-11.2 ± 1.3 μg/mL, P < .0001) and HbA₁(c) and cortisol levels were significantly increased (5.61 ± 0.1-5.8 ± 0.1%, P < .0001, 11.3 ± 0.8-14.7 ± 1.3 μg/dL, P = .003, respectively). In patients receiving spironolactone, there was a significant positive correlation between the change in cortisol and the change in HbA₁(c) (r = 0.489, P = .003). In contrast, in patients receiving eplerenone (n = 73), plasma levels of adiponectin, HbA₁(c) and cortisol did not change. CONCLUSION These findings indicated that the metabolic effect of eplerenone differed from that of spironolactone and that eplerenone had a superior metabolic effect especially on HbA₁(c) in CHF patients.

Relationship between renal function and serum cardiac troponin T in patients with chronic heart failure

Both serum cardiac troponin T (cTnT) and renal function are prognostic predictors in patients with chronic heart failure (CHF). We aimed to evaluate the relationship between renal function and serum cTnT.

Serum Cortisol as a Useful Predictor of Cardiac Events in Patients with Chronic Heart Failure: the Impact of Oxidative Stress

Background—The pathophysiological role of cortisol, which binds to the mineralocorticoid receptor with an affinity equal to that of aldosterone (ALD), may be influenced by oxidative stress in patients with chronic heart failure. We evaluated cardiac event prediction using cortisol levels in chronic heart failure, in comparison with ALD, adrenocorticotropic hormone, and brain natriuretic peptide (BNP), and the impact of oxidative stress. Methods and Results—We measured the plasma levels of biomarkers such as BNP, ALD, adrenocorticotropic hormone, serum cortisol, and oxidized low-density lipoprotein (oxLDL), a biomarker of oxidative stress, in 319 consecutive symptomatic patients with chronic heart failure, and we followed these patients for a mean period of 33 months. During the follow-up period, 29 patients had cardiac events (death or hospitalization). Plasma levels of BNP, ALD, adrenocorticotropic hormone, oxLDL, and serum cortisol (16.8±1.8 &mgr;g/dL versus 12.4±0.3 &mgr;g/dL, P=0.01) were significantly higher in patients with cardiac events than in those without cardiac events. On stepwise multivariate analyses, high levels of BNP (P=0.0003), renin (P=0.002), cortisol (P=0.02), and oxLDL (P=0.002) were independent predictors of cardiac events, but ALD and adrenocorticotropic hormone levels were not. In patients with serum cortisol ≥12.5 &mgr;g/dL, the hazard ratio of cardiac events in patients with oxLDL ≥12 U/mL was 3.5 compared with that in patients with oxLDL <12 U/mL (P=0.008). Conclusions—These findings indicate that serum cortisol levels were a complementary and incremental cardiac event risk predictor in combination with BNP in patients with chronic heart failure and that cardiac event prediction based on cortisol levels was influenced by oxidative stress.

Serum Cortisol as a Useful Predictor of Cardiac Events in Patients With Chronic Heart FailureCLINICAL PERSPECTIVE

Background—The pathophysiological role of cortisol, which binds to the mineralocorticoid receptor with an affinity equal to that of aldosterone (ALD), may be influenced by oxidative stress in patients with chronic heart failure. We evaluated cardiac event prediction using cortisol levels in chronic heart failure, in comparison with ALD, adrenocorticotropic hormone, and brain natriuretic peptide (BNP), and the impact of oxidative stress. Methods and Results—We measured the plasma levels of biomarkers such as BNP, ALD, adrenocorticotropic hormone, serum cortisol, and oxidized low-density lipoprotein (oxLDL), a biomarker of oxidative stress, in 319 consecutive symptomatic patients with chronic heart failure, and we followed these patients for a mean period of 33 months. During the follow-up period, 29 patients had cardiac events (death or hospitalization). Plasma levels of BNP, ALD, adrenocorticotropic hormone, oxLDL, and serum cortisol (16.8±1.8 &mgr;g/dL versus 12.4±0.3 &mgr;g/dL, P=0.01) were significantly higher in patients with cardiac events than in those without cardiac events. On stepwise multivariate analyses, high levels of BNP (P=0.0003), renin (P=0.002), cortisol (P=0.02), and oxLDL (P=0.002) were independent predictors of cardiac events, but ALD and adrenocorticotropic hormone levels were not. In patients with serum cortisol ≥12.5 &mgr;g/dL, the hazard ratio of cardiac events in patients with oxLDL ≥12 U/mL was 3.5 compared with that in patients with oxLDL <12 U/mL (P=0.008). Conclusions—These findings indicate that serum cortisol levels were a complementary and incremental cardiac event risk predictor in combination with BNP in patients with chronic heart failure and that cardiac event prediction based on cortisol levels was influenced by oxidative stress.

Prognostic value of serial measurements of highly sensitive cardiac troponin I in stable outpatients with nonischemic chronic heart failure.

BACKGROUND Cardiac troponin I (cTnI) is a useful biomarker in patients with chronic heart failure (CHF), and a highly sensitive cTnI (hs-cTnI) commercial assay has become available. However, the prognostic role of serial measurements of hs-cTnI in stable outpatients with CHF remains unknown. METHODS At entry to the study, we evaluated 95 stable outpatients with nonischemic CHF showing a serum hs-cTnI (Centaur TnI-Ultra [Siemens Medical Solution Diagnostics, New York, NY], lower limit of detection 0.006 ng/mL) value ≥0.006 ng/mL. To evaluate the role of repetitive measurements of hs-cTnI, we performed echocardiography and measured serum levels of cTnI and N-terminal proBNP at baseline and 6 months later and then prospectively followed up these patients for 4.25 years. RESULTS During long-term follow-up, there were 27 cardiac deaths. On multivariate analyses, high plasma N-terminal pro-brain natriuretic peptide (≥711 pg/mL, P = .0008), high serum hs-cTnI at baseline (≥0.03 ng/mL, P = .0011), and an increase in hs-cTnI (Δhs-cTnI ≥0 ng/mL, P = .022) after 6 months were independent significant prognostic predictors. The hazard ratio for mortality of patients with high hs-cTnI (≥0.03 ng/mL) and an increase in hs-cTnI (Δhs-cTnI ≥0 ng/mL) was 3.59 (95% CI 1.3-9.9, P = .014) compared with that of those with high hs-cTnI (≥0.03 ng/mL) and a decrease in hs-cTnI (Δhs-cTnI <0 ng/mL). CONCLUSIONS These findings indicated that not only the serum concentration of hs-cTnI at baseline but also an increase in hs-cTnI were independent and useful prognostic predictors in patients with nonischemic CHF.

Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension

In general, treatment with most angiotensin receptor blockers (ARBs) increases plasma angiotensin II (Ang II) level because of a lack of negative feedback on renin activity. Olmesartan is a potential ARB inducing activation of angiotensin-converting enzyme 2 (ACE2) that hydrolyzes Ang II to Ang 1–7, and has shown a beneficial effect on ventricular remodeling. Indeed, a previous study reported that olmesartan treatment resulted in decreased plasma levels of Ang II and aldosterone. However, there has not yet been a study showing the relationship of chronic effects of olmesartan on Ang II and the left ventricular mass index (LVMI) in comparison with those of other ARB.A total of 50 stable outpatients with essential hypertension who had received candesartan for more than 1 year were randomized into two groups: control group (n=25): continuous candesartan treatment at a stable dose; and olmesartan group (n=25): candesartan (8 mg day−1) was changed to olmesartan given at a dose of 20 mg day−1. There was no difference in the baseline characteristics between the two groups. In the control group, there were no significant changes in blood pressure, LVMI or biomarkers during 12 months of study. In the olmesartan group, blood pressure did not change and plasma levels of Ang II decreased during 12 months of study, whereas LVMI was significantly decreased after 12 months (135±36 vs. 123±29 g m−2; P<0.01).These findings indicate that replacing candesartan with olmesartan decreased LVMI in association with a sustained decrease of plasma Ang II over a 12-month period without changing blood pressure or plasma aldosterone in patients with essential hypertension.

Effect of simvastatin vs. rosuvastatin on adiponectin and haemoglobin A1c levels in patients with non‐ischaemic chronic heart failure

To compare the effects of lipophilic simvastatin and hydrophilic rosuvastatin on plasma adiponectin and glycated haemoglobin A1c (HbA1c) levels in patients with non‐ischaemic chronic heart failure (NICHF).

Transcardiac increase in norepinephrine and prognosis in patients with chronic heart failure.

No previous study has compared the transcardiac gradient of norepinephrine (NE) and the prognosis of patients with chronic heart failure (CHF).

Long-term effect of efonidipine therapy on plasma aldosterone and left ventricular mass index in patients with essential hypertension.

A certain percentage of aldosterone (ALD) breakthrough generally occurs in patients with hypertension and chronic heart failure and is an important issue during long-term treatment with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB). It has been reported that efonidipine decreases the plasma levels of ALD. However, the long-term effects of efonidipine on the plasma levels of ALD and the left ventricular mass index (LVMI) remain unknown in patients with hypertension. Sixty stable outpatients with essential hypertension who had received amlodipine and ACE-I or ARB for more than 1 year were randomized into two groups (amlodipine group (n=30): continuous amlodipine treatment at a stable dose; efonidipine group (n=30): amlodipine (5 mg day−1) was changed to efonidipine at a dose of 40 mg day−1). There was no difference in their baseline characteristics including the LVMI and plasma levels of ALD. In the amlodipine group, there were no significant changes in blood pressure, LVMI or plasma levels of ALD for 18 months. In the efonidipine group, blood pressure did not change after replacement of amlodipine with efonidipine, although there was a significant decrease in the plasma levels of ALD after 6 months. The decrease in ALD was sustained for 18 months and LVMI was significantly decreased after 18 months (121±25 vs. 114±21 g m−2, P<0.05). There was a significant correlation between the changes in LVMI and % changes of ALD in the efonidipine group. These findings indicate that the effect of efonidipine on the suppression of plasma ALD was sustained for at least 18 months and that long-term efonidipine therapy decreases LVMI in patients with essential hypertension.