TIMP-1 in the prognosis of patients who underwent coronary artery bypass surgery: a 12-year follow-up study.

Introduction: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been linked to clinical outcomes in patients with coronary artery disease (CAD). However, the prognostic value of TIMP-1 in patients with CAD who underwent coronary artery bypass grafting (CABG) has not been elucidated. We aimed to investigate the correlations of TIMP-1 with high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the long-term prognosis of consecutive patients who underwent CABG. Methods: A total of 234 patients (age: 70.4 ± 10.5 years, 84.6% men) with CAD who underwent CABG were prospectively enrolled. Preoperative levels of MMPs, TIMP-1, hs-CRP, and NT-proBNP were recorded. Major adverse cardiovascular events (MACE) were defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Results: During a median follow-up of 12.1 years, 120 deaths were recorded. The deceased were older, had more manifest acute coronary syndrome (ACS), a lower left ventricular ejection fraction (LVEF), and an estimated glomerular filtration rate (eGFR), but significantly higher MMP13, TIMP-1, hs-CRP, and NT-proBNP compared with the survivors. After adjusting for age, sex, manifest ACS, eGFR, LVEF, total cholesterol, and triglycerides, TIMP-1 (hazard ratio and 95% confidence intervals per SD: 1.506, 1.183-1.917), hs-CRP (1.349, 1.183-1.561), and NT-ProBNP (1.707, 1.326-2.199) were all independently associated with all-cause mortality. The mediation analysis revealed that the mortality risks of TIMP-1 were partially mediated by NT-proBNP (62.2%) and hs-CRP (25.3%). The associations of TIMP-1 with MACE were partially mediated by NT-proBNP (54.4%) but not hs-CRP. Conclusions: TIMP-1 was an independent predictor of long-term outcomes after CABG, with possible roles in subclinical inflammation and postoperative cardiac remodeling.

Increased Nighttime Pulse Pressure Variability but Not Ambulatory Blood Pressure Levels Predicts 14-Year All-Cause Mortality in Patients on Hemodialysis.

Increased short-term blood pressure (BP) variability is associated with adverse cardiovascular outcomes in patients with hypertension. The present study investigated the long-term prognostic significance of the short-term blood pressure variability in patients on hemodialysis. A total of 149 patients (53.0% male; mean age: 54.5±15.1 years) receiving regular hemodialysis for >6 months were enrolled. They completed a 44-hour (excluding the hemodialysis session) ambulatory BP monitoring and comprehensive hemodynamic assessments, including carotid-femoral pulse wave velocity and pressure waveform decomposition (forward and backward wave amplitude). Blood pressure variability parameters, including average real variability (ARV) of systolic BP, diastolic BP, and pulse pressure (ARVp) during daytime, nighttime, and overall 44 hours were calculated. During a median follow-up of 14 years, 78 deaths (52.4%) were confirmed. In multivariable Cox regression analysis, none of the ambulatory BP parameters were predictive of mortality. In contrast, nighttime ARVp was consistently and significantly associated with all-cause mortality in multivariable Cox models adjusting for age, sex, albumin, hemodialysis treatment adequacy, and 44-hour systolic BP (continuous variable analysis, per 1-SD, hazard ratio=1.348; 95% CI, 1.029-1.767; categorical variable analysis, ≥8.5 versus <8.5 mm Hg; hazard ratio=1.825; 95% CI, 1.074-3.103). Forward wave amplitude and 44-hour systolic BP were identified as the 2 most important determinants of nighttime ARVp. Addition of nighttime ARVp to the base model significantly improved prediction of all-cause mortality (Net reclassification improvement =0.198; P=0.0012). In hemodialysis patients, increased short-term nighttime pulse pressure variability but not ambulatory BP levels were significantly predictive of long-term all-cause mortality.

Prognostic Comparison of the Estimations of Renal Function in Patients With Acute Heart Failure.

BACKGROUND: The prognostic significance of the eGFR calculated by either the four-level Race Chronic Kidney Disease-Epidemiology Collaboration study equation (CKD-EPI4R) or the Chinese-modified Modification of Diet in Renal Disease equation (cMDRD) has not been compared in Asian populations with acute heart failure (AHF).Methods and Results:A total of 3,044 patients hospitalized for AHF were enrolled. The National Death Registry was linked to identify deaths within a 5-year follow-up. Net reclassification improvement (NRI) was calculated to compare the prognostic value of either eGFR equation. During a median follow-up of 23.3 months, 1,424 (47%) patients died. Both eGFRcMDRDand eGFRCKD-EPI4Rwere independently predictive of death in the total study population (hazard ratio and 95% confidence intervals per 1-SD: 0.76, 0.71-0.81 and 0.74, 0.70-0.79, respectively), and in the subgroups of either reduced (HFrEF) or preserved (HFpEF) ejection fraction, after accounting for important confounders. With reference to eGFRcMDRD, eGFRCKD-EPI4Rmay improve the NRI by 2.0% (0.8-3.2%) for the prediction of death. The prognostic value of the CKD stages categorized by eGFRCKD-EPI4Rsignificantly outperformed eGFRcMDRDwith a categorical NRI of 9.5% (4.7-14.3%) in the total study population, 11.5% in HFrEF, and 8.3% in HFpEF. CONCLUSIONS: Both eGFRcMDRDand eGFRCKD-EPI4Rwere independently associated with long-term survival in patients with AHF. However, the CKD stages derived from eGFRCKD-EPI4Rimproved the risk stratification of death, compared with eGFRcMDRD.

Value of Excess Pressure Integral for Predicting 15-Year All-Cause and Cardiovascular Mortalities in End-Stage Renal Disease Patients.

BACKGROUND: The excess pressure integral (XSPI), derived from analysis of the arterial pressure curve, may be a significant predictor of cardiovascular events in high-risk patients. We comprehensively investigated the prognostic value of XSPI for predicting long-term mortality in end-stage renal disease patients undergoing regular hemodialysis. METHODS AND RESULTS: A total of 267 uremic patients (50.2% female; mean age 54.2±14.9 years) receiving regular hemodialysis for more than 6 months were enrolled. Cardiovascular parameters were obtained by echocardiography and applanation tonometry. Calibrated carotid arterial pressure waveforms were analyzed according to the wave-transmission and reservoir-wave theories. Multivariable Cox proportional hazard models were constructed to account for age, sex, diabetes mellitus, albumin, body mass index, and hemodialysis treatment adequacy. Incremental utility of the parameters to risk stratification was assessed by net reclassification improvement. During a median follow-up of 15.3 years, 124 deaths (46.4%) incurred. Baseline XSPI was significantly predictive of all-cause (hazard ratio per 1 SD 1.4, 95% confidence interval 1.15-1.70, P=0.0006) and cardiovascular mortalities (1.47, 1.18-1.84, P=0.0006) after accounting for the covariates. The addition of XSPI to the base prognostic model significantly improved prediction of both all-cause mortality (net reclassification improvement=0.1549, P=0.0012) and cardiovascular mortality (net reclassification improvement=0.1535, P=0.0033). XSPI was superior to carotid-pulse wave velocity, forward and backward wave amplitudes, and left ventricular ejection fraction in consideration of overall independent and incremental prognostics values. CONCLUSIONS: In end-stage renal disease patients undergoing regular hemodialysis, XSPI was significantly predictive of long-term mortality and demonstrated an incremental value to conventional prognostic factors.

Prognostic significance of mechanical biomarkers derived from pulse wave analysis for predicting long-term cardiovascular mortality in two population-based cohorts.

BACKGROUND: Numerous mechanical biomarkers derived from pulse wave analysis (PWA) have been proposed to predict cardiovascular outcomes. However, whether these biomarkers carry independent prognostic value and clinical utility beyond traditional cardiovascular risk factors hasn't been systematically evaluated. We aimed to investigate the additive utility of PWA-derived biomarkers in two independent population-based cohorts. METHODS: PWA on central arterial pressure waveforms obtained from subjects without a prior history of cardiovascular diseases of two studies was conducted based on the wave transmission and reservoir-wave theory: firstly in the Kinmen study (1272 individuals, a median follow-up of 19.8years); and then in the Cardiovascular Disease Risk Factors Two-Township Study (2221 individuals, median follow-up of 10years). The incremental value of the biomarkers was evaluated by net reclassification index (NRI). RESULTS: In multivariate Cox analyses accounting for age, gender, body mass index, systolic blood pressure, fasting glucose, high-density- and low-density-lipoprotein cholesterol, and smoking, only systolic (SC) and diastolic rate constant (DC) of reservoir pressure could independently and consistently predict cardiovascular mortality in both cohorts and the combined cohort (SC: hazard ratio 1.18 [95% confidence interval 1.08-1.28, p<0.001; DC: 1.18 [1.09-1.28], p<0.001]. Risk prediction estimates in traditional risk prediction models were significantly more accurate when incorporating peak of reservoir pressure (NRI=0.049, p=0.0361), SC (NRI=0.043, p=0.0236) and DC (NRI=0.054, p=0.047). CONCLUSIONS: Of all PWA-derived biomarkers, SC and DC were consistently identified as valuable parameters for incremental cardiovascular risk prediction in two large prospective cohorts.