Dai-Yin Lu

Determinants and Prognostic Impact of Hyperuricemia in Hospitalization for Acute Heart Failure

BACKGROUND Hyperuricemia is a prognostic factor in patients with chronic heart failure, but whether uric acid level can predict clinical outcome of acute heart failure (AHF) remains to be elucidated. We therefore investigated the association of uric acid with mortality in patients hospitalized for AHF. METHODSANDRESULTS Data for patients hospitalized for AHF were drawn from an intramural registry. Biochemistry data, echocardiographic characteristics, and uric acid level were collected. National Death Registry was linked for the identification of mortality data. Among a total of 1,835 participants (age, 75 ± 13 years, 68% men), 794 patients died during follow-up. Patients who died were older, had lower hemoglobin and estimated glomerular filtration rate, and higher pulmonary artery systolic pressure, NT-proBNP, and uric acid. Uric acid was a significant predictor of mortality on univariate analysis (HR per 1 SD, 1.18; 95% CI: 1.11-1.26) and in multivariate Cox models (HR, 1.15; 95% CI: 1.02-1.29). Survival analysis showed an increasing risk of death along the quartile distribution of uric acid level. Given renal function, cardiac performance, and kidney perfusion as major determinants of hyperuricemia, the prognostic impact of uric acid level was diminished as renal function deteriorated. CONCLUSIONS Uric acid level was an independent predictor of mortality in patients hospitalized for AHF, but the prognostic impact of hyperuricemia was attenuated by worsening renal function.

Hyponatremia and Worsening Sodium Levels Are Associated With Long‐Term Outcome in Patients Hospitalized for Acute Heart Failure

Background Hyponatremia predicts poor prognosis in patients with acute heart failure (AHF). However, the association of the severity of hyponatremia and changes of serum sodium levels with long‐term outcome has not been delineated. Methods and Results The study population was drawn from the HARVEST registry (Heart Failure Registry of Taipei Veterans General Hospital), so that patients hospitalized for acute heart failure (AHF) composed this study. The National Death Registry was linked to identify the clinical outcomes of all‐cause mortality and cardiovascular death, with a follow‐up duration of up to 4 years. Among a total of 2556 patients (76.4 years of age, 67% men), 360 had on‐admission hyponatremia, defined as a serum sodium level of <135 mEq/L on the first day of hospitalization. On‐admission hyponatremia was a predictor for all‐cause mortality (hazard ratio and 95% CI: 1.43, 1.11–1.83) and cardiovascular mortality (1.50, 1.04–2.17), independent of age, sex, hematocrit, estimated glomerular filtration rate, left ventricular ejection fraction, and prescribed medications. Subjects with severe hyponatremia (<125 mEq/L) would even have worse clinical outcomes. During hospitalization, a drop of sodium levels of >3 mEq/L was associated with a marked increase of mortality than those with minimal or no drop of sodium levels. In addition, subjects with on‐admission hyponatremia and drops of serum sodium levels during hospitalization had an incremental risk of death (2.26, 1.36–3.74), relative to those with normonatremia at admission and no treatment‐related drop of serum sodium level in the fully adjusted model. Conclusions On‐admission hyponatremia is an independent predictor for long‐term outcomes in patients hospitalized for AHF. Combined the on‐admission hyponatremia with drops of serum sodium levels during hospitalization may make a better risk assessment in AHF patients.

Wave reflections, arterial stiffness, heart rate variability and orthostatic hypotension

Increased arterial stiffness and wave reflections are independently associated with orthostatic hypotension (OH). This study investigated whether heart rate variability (HRV) is also involved in the modulation of orthostatic blood pressure (BP) change. A total of 429 subjects (65.1±16.4 years, 77.4% men) were enrolled in this study. OH was defined as a ⩾20 mm Hg decrease in brachial systolic blood pressure (SBP) or a ⩾10 mm Hg diastolic blood pressure (DBP) decrease upon standing. Measurements of carotid–femoral pulse wave velocity (cf-PWV) and the amplitude of the reflected pressure wave from a decomposed carotid pressure wave (Pb) were obtained by carotid tonometry in the supine position. The power spectrum from a 5-min recording of an electrocardiogram at rest was analyzed to provide components in the high frequency (HF) and low frequency (LF) ranges. Subjects with OH (n=59, 13.8%) had significantly higher cf-PWV and Pb and significantly lower LogHF and LogLF than those without OH (n=370). The cf-PWV, Pb, LogHF and LogLF were significantly associated with postural SBP and DBP changes. Furthermore, cf-PWV but not Pb was significantly associated with LogHF and LogLF. Multivariate analysis showed that Pb (odds ratio (OR) per 1 s.d. 1.65, 95% confidence interval (CI) 1.282–2.137; P=0.003) and LogHF (OR 0.628, 95% CI 0.459–0.860, P=0.004), but not cf-PWV (OR 1.279, 95% CI 0.932–1.755, P=0.128), were significant independent determinants of OH. Increased wave reflections may predispose OH independently of arterial stiffness and HRV. In contrast, increased arterial stiffness may cause OH through the modulation of HRV.

Wave Reflections, Arterial Stiffness, and Orthostatic Hypotension

BACKGROUND The effect of wave reflections on blood pressure change associated with posture remains unclear. We therefore applied a wave separation technique to investigate the relations of the backward pressure wave amplitude with orthostatic pressure changes and orthostatic hypotension (OH). METHODS We analyzed data from 613 subjects who had participated in our hemodynamic studies. Measurements of brachial systolic (SBP) and diastolic blood pressures (DBP), carotid-femoral pulse wave velocity (cf-PWV), and backward pressure wave amplitude from a decomposed carotid pressure wave (Pb) were obtained at supine position. SBP and DBP were measured again 3 minutes after standing. OH was defined as a fall of ≥20 mm Hg in SBP and/or ≥10 mm Hg in DBP. RESULTS Subjects with OH (n = 100) were characterized with significantly higher supine SBP and DBP and significantly lower standing SBP and DBP when compared with subjects without OH. Subjects with OH were also characterized with significantly higher cf-PWV and Pb. cf-PWV and Pb separately were significantly associated with the orthostatic SBP change in univariable and multivariable analyses. Also, cf-PWV and Pb separately were significant predictors of OH in univariable and multivariable analyses. cf-PWV predicted OH in the younger but less so in the older subgroup, whereas Pb demonstrated similar prediction in both subgroups. In a final multivariable model, both cf-PWV and Pb were significant independent predictors of OH. CONCLUSIONS Wave reflections are an independent determinant of orthostatic SBP change and OH in both younger and older subjects.

Usefulness of the CHADS2 Score for Prognostic Stratification in Patients With Coronary Artery Disease Having Coronary Artery Bypass Grafting

Current risk model for long-term survival prediction in isolated coronary artery bypass graft surgery is complicated, whereas a simple useful model is still lacking. We aim to investigate if CHADS2 score could predict long-term outcome for patients after coronary artery bypass graft surgery. From 2000 to 2007, we identified a study cohort consisting of patients who underwent coronary bypass surgery in the Taiwan National Health Insurance Research Database. After operation, all cases were followed to track the incidence of major adverse cardiovascular events and overall mortality. During a mean 5.1-year follow-up, 638 patients experienced major cardiovascular events. Six hundred twenty-five patients passed away at the end of follow-up, whereas 204 died of cardiovascular cause. Subjects with higher CHADS2 scores had significantly higher 10-year overall mortality and cardiovascular death, as well as the incidence of major adverse cardiovascular events. After adjustment with co-morbid condition and prescribed medications, CHADS2 was independently associated with increased risks of all-cause mortality (hazard ratio 1.36, 95% CI 1.29 to 1.44) and cardiovascular mortality (hazard ratio 1.37, 95% CI 1.24 to 1.52). In conclusion, CHADS2 score provides a quick and useful tool in predicting long-term outcome for patients after coronary artery bypass surgery.

Heart Rate Variability Is Associated with Exercise Capacity in Patients with Cardiac Syndrome X.

Heart rate variability (HRV) reflects the healthiness of autonomic nervous system, which is associated with exercise capacity. We therefore investigated whether HRV could predict the exercise capacity in the adults with cardiac syndrome X (CSX). A total of 238 subjects (57±12 years, 67.8% men), who were diagnosed as CSX by the positive exercise stress test and nearly normal coronary angiogram were enrolled. Power spectrum from the 24-hour recording of heart rate was analyzed in frequency domain using total power (TP) and spectral components of the very low frequency (VLF), low frequency (LF) and high frequency (HF) ranges. Among the study population, 129 subjects with impaired exercise capacity during the treadmill test had significantly lower HRV indices than those with preserved exercise capacity (≥90% of the age predicted maximal heart rate). After accounting for age, sex, and baseline SBP and heart rate, VLF (odds ratio per 1SD and 95% CI: 2.02, 1.19–3.42), LF (1.67, 1.10–2.55), and TP (1.82, 1.17–2.83) remained significantly associated with preserved exercise capacity. In addition, increased HRV indices were also associated with increased exercise duration, rate-pressure product, and heart rate recovery, independent of age, body mass index, and baseline SBP and heart rate. In subgroup analysis, HRV indices demonstrated similar predictive values related to exercise capacity across various subpopulations, especially in the young. In patients with CSX, HRV was independently associated with exercise capacity, especially in young subjects. The healthiness of autonomic nervous system may have a role in modulating the exercise capacity in patients with CSX.

Additive Value of Heart Rate Variability in Predicting Obstructive Coronary Artery Disease Beyond Framingham Risk

BACKGROUND Heart rate variability (HRV) is usually reduced in patients with CAD. We therefore investigated whether reduced HRV is predictive of angiographic CAD beyond Framingham risk in patients with stable angina. METHODSANDRESULTS A total of 514 patients (age, 66.1 ± 14.3 years, 358 men) were enrolled. Holter ECG was performed before catheterization, and 24-h HRV was analyzed in both the frequency domain (VLF, LF, HF and total power) and the time domain (SDNN, SDANN, RMSSD and pNN20). Angiographic CAD was defined as ≥ 50% diameter reduction of 1 or more coronary arteries. On coronary angiography 203 patients (39.6%) had angiographic CAD. Patients with CAD had significantly higher Framingham risk and lower HRV according to both frequency and time domain parameters. After controlling for age, gender, heart rate, SBP, renal function, lipids and Framingham risk, reduced HRV indices remained predictors of CAD (OR, 95% CI for LF, HF, SDNN, RMSSD and pNN20: 0.81, 0.66-0.99; 0.77, 0.63-0.94; 0.75, 0.59-0.96; 0.72, 0.58-0.88; and 0.76, 0.62-0.94, respectively). On subgroup analysis, HRV parameters appeared to be predictive of CAD only in subjects with high Framingham risk or diabetes. CONCLUSIONS Reduced HRV is predictive of CAD in patients with stable angina, independent of traditional risk factors and Framingham risk. The predictive value of HRV may be relevant only in subjects with high Framingham risk or diabetes.

Hemographic indices are associated with mortality in acute heart failure

Hemographic indices have been associated with clinical outcomes in patients with chronic heart failure. We therefore investigated the prognostic values of hemographic indices in patients hospitalized for acute heart failure (AHF). Patients hospitalized primarily for AHF were drawn from an intramural registry. Hemographic indices, including white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratio, reciprocal of lymphocyte (RL) and platelet-to-lymphocyte ratio were recorded. Among a total of 1923 participants (mean age 76 ± 12 years, 68% men), 875 patients died during a mean follow-up of 28.6 ± 20.7 months. Except for white blood cell counts, all the other hemographic indices were related to mortality, independently. In a forward stepwise Cox regression analysis among hemographic indices, RL was the strongest predictor (HR and 95% CI per-1SD:1.166,1.097–1.240) for mortality, after accounting for confounders. However, conditioned on the survivals, the hemographic indices were independently related to mortality within 3 years of follow-up, rather than beyond. Hemographic indices were independent risk factors of mortality in patients hospitalized for AHF, especially in patients with impaired left ventricular systolic function. As an acute presentation of inflammation, hemographic indices might be useful to identify subjects at risk of mortality soon after the index hospitalization.

Abnormal Pulsatile Hemodynamics in Hypertensive Patients With Normalized 24-Hour Ambulatory Blood Pressure by Combination Therapy of Three or More Antihypertensive Agents.

It remains uncertain whether intensive antihypertensive therapy can normalize pulsatile hemodynamics resulting in minimized residual cardiovascular risks. In this study, office and 24‐hour ambulatory systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, carotid‐femoral pulse wave velocity (PWV), and forward (Pf) and reflected (Pb) pressure wave from a decomposed carotid pressure wave were measured in hypertensive participants. Among them, 57 patients whose 24‐hour SBP and DBP were normalized by three or more classes of antihypertensive medications were included. Another 57 age‐ and sex‐matched normotensive participants were randomly selected from a community survey. The well‐treated hypertensive patients had similar 24‐hour SBP, lower DBP, and higher PP values. The treated patients had higher PWV (11.7±0.3 vs 8.3±0.2 m/s, P<.001), Pf, Pb, Pb/Pf, and left ventricular mass index values. After adjustment for age, sex, body mass index, and office SBP, the differences for PWV, Pb, and Pb/Pf remained significant. Hypertensive patients whose 24‐hour SBP and DBP are normalized may still have markedly increased arterial stiffness and wave reflection.

ISH NIA PS 02-07 The predictive value and determinants of pulse pressure in patients hospitalized for acute heart failure with preserved ejection fraction

Objective: The pulse pressure (PP) is a complex entity and determined by both ventricular and arterial function. In heart failure with preserved ejection fraction (HFpEF), the dominant effect of PP was associated with increased arterial stiffness. But the role of on-admission PP in acute heart failure (AHF) remains elucidated. We therefore investigated the associations of PP with mortality in patients hospitalized for AHF with pEF. Design and Method: Patients hospitalized for AHF with EF > 50% were composed of this intramural registry. Biochemistry data, echocardiographic characteristics, and blood pressure on-admission were collected. National Death Registry was linked for mortality. Results: Among a total of 1287 participants (age 79.2 ± 10.8 years, 61% men), 496 patients died during a mean follow up duration of 25.5 ± 19.7 months. The relation between PP and mortality in the patients with preserved EF may be non-linear. (Figure. 1) Risk decreased as PP increased up to 80 mmHg [HR and 95% CI per-10 mmHg, 0.913 (0.842–0.991)] after accounting for age, sex, hemoglobin, eGFR, sodium, relative lymphocytes, prescriptions of medication, and the presence of atrial fibrillation. When PP was beyond 80 mmHg, the predictive value of PP was insignificant [1.074 (0.969–1.012)]. In a stepwise multiple linear regression analysis, age, heart rate, eGFR, LV mass, pulmonary artery systolic pressure and hemoglobin level constructed the maximal predictive model for PP levels. Conclusions: When the PP was below 80 mmHg, the lower level was linked to the poor outcome in AHF with preserved EF. It may reflect that LV performance was decreased in the acute decompensated condition, even if the baseline LV systolic function was preserved. When the PP was above 80mmHg, the association between PP level and mortality was absent. The possible explain was that both the LV performance and arterial stiffness can contribute to the PP and they had opposite effects of long term outcome in patients hospitalized for AHF. Figure. No caption available.