Yao-Yi Huang

Left Ventricular Systolic Strain in Chronic Kidney Disease and Hemodialysis Patients

Background: The impact of chronic kidney disease (CKD) and hemodialysis on heart function is not fully understood. We aimed to investigate the influence of different stages of CKD and maintenance hemodialysis on heart function. Methods: One hundred fifty-three patients were categorized into 3 subgroups [56 without CKD as controls; 37 with moderate-advanced CKD, stages 3, 4 or 5, and 60 with end-stage renal disease (ESRD) undergoing maintenance hemodialysis]. Left ventricular (LV) function was assessed by conventional echocardiography and 2-dimensional speckle-tracking echocardiography with strain analysis (2D strain analysis). Results: There was no significant difference of gender, age and LV ejection fraction among groups. Compared with controls, global peak systolic longitudinal strain (GSl), circumferential strain and strain rate were decreased in the CKD group. Along with the decline of renal function, GSl deteriorated. Moreover, compared with moderate-advanced CKD patients, GSl, circumferential strain and strain rate were better in ESRD group receiving maintenance hemodialysis. Conclusions: Worsening renal function was associated with a reduction of systolic function, and could be quantified by 2D strain analysis. The hemodialysis patients have better LV systolic function than the moderate-advanced CKD patients.

Plasma vascular endothelial growth factor as a marker for early vascular damage in hypertension

Elevation of plasma VEGF (vascular endothelial growth factor) has been noted in patients with hypertension or atherosclerosis. VEGF has been regarded as a marker for endothelial dysfunction. However, the role of VEGF in hypertension-induced vascular injury and its relationship with endothelial function have not been studied. This study included 20 untreated hypertensive men with grade 1 or 2 hypertensive retinopathy, 10 untreated hypertensive men without hypertensive retinopathy and 10 healthy controls. None of the hypertensive patients had diabetes, renal impairment or overt vascular diseases. Plasma VEGF and adhesion molecules were measured using ELISAs. Endothelial function was measured by FMD (flow-mediated vasodilation) of the brachial artery. Plasma levels of VEGF, excluding adhesion molecules, were significantly higher in hypertensive patients with retinopathy when compared with patients without retinopathy (152.4+/-80.8 pg/ml versus 104.7+/-27.2 pg/ml, P = 0.035) or controls (152.4+/-80.8 pg/ml versus 98.9+/-23.7 pg/ml, P = 0.025). Levels of FMD were significantly lower in hypertensive patients than controls, but there were no significant differences between patients with or without retinopathy. Degrees of FMD were inversely correlated with VEGF levels (r = -0.351, P = 0.031). Elevation of plasma VEGF was associated with hypertensive retinopathy. Plasma VEGF could be used as a marker of early vascular damage induced by hypertension.

Uric acid is an independent predictor of arterial stiffness in hypertensive patients

Increased arterial stiffness is an important marker for target organ damage in essential hypertension. Both serum uric acid (UA) and C-reactive protein (CRP) were reported to be associated with target organ damage. However, the influences of UA and CRP on large arterial stiffness were not well elucidated. This study included 200 essential hypertension patients (64 women) whose age was between 20 and 50 years old (mean age 41 ± 8 years). None of the patients had diabetes mellitus or overt end-organ damage. Arterial stiffness was assessed by pulse-wave velocity (PWV) measured by tonometry from carotid to radial artery. Serum UA, high-sensitivity CRP (hsCRP), glucose, insulin, and lipid profiles were measured at the same time in each patient. PWV levels were significantly correlated with mean blood pressure (r = 0.245, P < 0.001), diastolic blood pressure (r = 0.323, P < 0.001), high-density lipoprotein (r = −0.169, P = 0.016), and UA (r = 0.234, P = 0.001), but not age, body mass index, blood sugar, insulin, low-density lipoprotein, triglyceride, and hsCRP. Pulsewave velocity levels were significantly higher in males (8.9 ± 1.2 vs 8.2 ± 1.2 m/s, P < 0.001) and smokers (9.3 ± 1.1 vs 8.5 ± 1.2 m/s, P < 0.001). Uric acid was significantly correlated with hsCRP (r = 0.294, P < 0.001). After multivariate analysis controlling for all possible confounding factors, UA (odds ratio 1.28, 95% confidence interval 1.02–1.61, P = 0.032) was still independently associated with increased PWV. In conclusion, UA but not hsCRP was independently associated with increased PWV in essential hypertension. Although UA was correlated with hsCRP, the association between UA and PWV was not through the effect of enhanced inflammation.

Stiffness index derived from digital volume pulse as a marker of target organ damage in untreated hypertension

Objective. An index of large artery stiffness (SIDVP) simply derived from the digital volume pulse (DVP) was developed recently. However, the role of the SIDVP in untreated hypertensive patients was not well elucidated. Methods. We enrolled 124 untreated hypertensive patients (mean age 55.4±13.1 years, 57 men). The DVP was measured in right index finger by a photoplethysmography. The SIDVP was formulated as body height divided by transition time from early systolic peak to the inflection point of reflection wave. Two functional indices of aortic compliance, stiffness index (SI) and distensibility (DI), were also used for measurement of aortic stiffness. Results. The SIDVP was significantly correlated with blood urea nitrogen (BUN), and left ventricular mass index (LVMI). Patients with vascular diseases had higher level of SIDVP (10.12±2.97 vs 8.45±1.78, p<0.001), SI (13.76±7.63 vs 10.87±8.88, p = 0.116), BUN (28.4±24.7 vs 14.5±4.6, p<0.001) and lower level of DI (1.34±0.88 vs 1.93±1.12, p = 0.010) than those without vascular diseases. By multivariate analysis, only the SIDVP was significantly associated with vascular diseases (OR 1.39, 95% CI 1.06–1.82, p = 0.016). Conclusions. SIDVP, SI and DI were significantly correlated with target organ damage in untreated hypertension. However, only the SIDVP was independently associated with presence of vascular diseases. SIDVP simply derived from the DVP can be used as a marker for risk stratification in untreated hypertensive patients.

Cilostazol enhances mobilization and proliferation of endothelial progenitor cells and collateral formation by modifying vasculo-angiogenic biomarkers in peripheral arterial disease

a Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan b Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan c Department of Internal Medicine, Tainan Municipal Hospital, Tainan, Taiwan d Department of Radiology, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan e Department of Emergency Medicine, National Cheng Kung University Hospital, Tainan, Taiwan f Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Association of central aortic pressures indexes with development of diabetes mellitus in essential hypertension.

BACKGROUND Diabetes mellitus (DM) and hypertension (HT) frequently coexist. Increased central aortic pressures indexes are associated with HT; however, possible associations of these indexes with future development of DM have never been studied in HT. METHODS We recruited 178 patients with uncomplicated nondiabetic HT in this study. Baseline glucose, insulin, lipid profiles, and central aortic pressure indexes obtained using applanation tonometry were measured at the beginning of the study. Patients were followed for new-onset DM. RESULTS After a mean follow-up period of 31 ± 12 months, 22 patients (12.4%) developed new-onset DM. In multivariate regression analyses adjusted for age, sex, and mean blood pressure (BP) in model 1, we found that central systolic BP (CSBP; hazard ratio 1.24, 95% CI 1.10-1.41, P < 0.001), and augmentation index (AIx) corrected at heart rate 75/min (AIx(75); hazard ratio 1.58, 95% CI 1.11-1.58, P < 0.05) were independent predictors for new-onset DM. After adjustment for age, sex, mean BP, glucose concentration, and β-blocker use in model 2, we found that CSBP (hazard ratio 1.36, 95% CI 1.19-1.55, P < 0.001) and AIx(75) (hazard ratio 1.71, 95% CI 1.16-2.52, P < 0.01) were independent predictors for new-onset DM. CONCLUSIONS CSBP and AIx(75) were independent factors for future DM in essential hypertensive patients. Increased central pressure indexes were associated with risk of DM in essential hypertension.

Association of adiponectin with procollagen type I carboxyterminal propeptide in non-diabetic essential hypertension

Objective. The serum concentration of procollagen type I carboxyterminal propeptide (PICP) is a good marker for collagen deposition in hypertension. Increased collagen deposition was associated with myocardial fibrosis and increased arterial stiffness. A decreased adiponectin level is associated with increased atherosclerosis. The role of adiponectin and its relation to PICP in essential hypertension have rarely been studied before. Methods. We recruited 188 non‐diabetic uncomplicated hypertensive patients (mean age: 41±7 years; 128 men). No patient had vascular complications or renal or liver diseases. Overnight fasting blood samples were collected to assess patient lipid profiles, blood sugar, insulin, high‐sensitivity C‐reactive protein (hsCRP), PICP and adiponectin. Carotid to radial pulse wave velocity (PWV) measured using tonometry was used as an index of arterial stiffness. Results. Adiponectin (r = −0.216, p = 0.003) and male gender (p<0.001) were independent determinants of PICP. Diastolic blood pressure (r = 0.422, p<0.001) and current smoking (p = 0.005) were independent determinants of PWV. PWV was significantly correlated with PICP (r = 0.156, p = 0.034). Adiponectin was significantly correlated with triglyceride (r = −0.276, p<0.001), high‐density lipoprotein (r = 0.262, p<0.001), the homeostasis model assessment (HOMA) index (r = −0.220, p = 0.002), hsCRP (r = −0.207, p = 0.004) and the body mass index (BMI) (r = −0.202, p = 0.005). After compensation with possible confounding factors, adiponectin was still significantly correlated with PICP (beta = −0.196, p = 0.006). Conclusion. Serum adiponectin may be a marker for metabolic syndrome in essential hypertension. Adiponectin was significantly negatively correlated with PICP. Metabolic syndrome probably plays an important role in increased collagen synthesis and arterial stiffness through the effects of decreased adiponectin in non‐diabetic essential hypertension.

Association of increased arterial stiffness and inflammation with proteinuria and left ventricular hypertrophy in non‐diabetic hypertensive patients

Objective. Both arterial stiffness and proteinuria are important markers for organ damage in hypertension. This study was planed to investigate the association between arterial stiffness and inflammation and to define the influences of proteinuria on arterial stiffness and inflammation in non‐diabetic hypertension. Methods. We enrolled 205 patients (mean age 41±8 years, 66 women) with essential hypertension noted for less than 5 years in this study. They did not have diabetes mellitus or any overt cardiac, vascular, or renal complications. Stiffness index (SI) derived from digital volume pulse was used for assessment of arterial stiffness. High‐sensitivity C‐reactive protein (hsCRP) was measured in each patient during enrollment. Left ventricular hypertrophy (LVH) was documented by electrocardiography and proteinuria was assessed by measuring 24‐h urine protein. Results. SI was significantly correlated with hsCRP (r = 0.166, p = 0.017). LVH was noted in 34 patients (17%). SI was significantly higher in patients with LVH (8.03±1.74 vs 7.19±1.19 m/s, p = 0.001). Proteinuria was noted in three patients with LVH. SI was gradually increased among patients without LVH, with LVH but not proteinuria, and with LVH and proteinuria (7.19±1.19, 7.68±1.21, 11.75±2.51 m/s respectively; p<0.001). HsCRP was also gradually increased among patients without LVH, with LVH but not proteinuria, and with LVH and proteinuria (0.20±0.24, 0.30±0.59, 1.56±1.58 mg/dl respectively; p<0.001). Conclusions. SI was significantly correlated with hsCRP. Arterial stiffness and inflammation were increased in association with proteinuria in non‐diabetic essential hypertension.

Increased C-reactive protein is associated with future development of diabetes mellitus in essential hypertensive patients

Coexistence of hypertension and diabetes mellitus (DM) increases the risk of cardiovascular disease. However, factors associated with future development of DM have not been well elucidated in patients already having essential hypertension. This study prospectively included 168 patients (mean age 41 ± 7 years, 112 men) with essential hypertension. All patients did not have DM and vascular or renal complications initially. Baseline demographic data, blood pressure, body mass index, and antihypertensive agents were carefully evaluated and serum high-sensitivity C-reactive protein (hsCRP) was measured at the beginning of the study. All of the patients were followed for at least 6 months. The study endpoint was occurrence of new DM. After a mean follow-up period of 32 ± 10 months, 22 subjects (13.1%) developed new DM. Patients with new DM had higher baseline glucose (105.2 ± 11.8 vs 94.2 ± 8.0 mg/dl, P < 0.001), triglyceride level (213.7 ± 112.4 vs 155.6 ± 83.2 mg/dl, P = 0.04), log hsCRP (0.31 ± 0.44 vs 0.19 ± 0.25 mg/dl, P = 0.016), and lower high-density lipoprotein (40.2 ± 7.8 vs 46.6 ± 14.4 mg/dl, P = 0.045). Total cholesterol, low-density lipoprotein, homeostasis model assessment index, and adiponectin were not different in patients with or without new DM. Among antihypertensive agents, only use of β-blocker was significantly associated with new DM (P = 0.008). Multivariate Cox regression analysis showed log hsCRP (hazard ratio [HR] 9.77, 95% confidence interval [CI] 2.97-32.10, P < 0.001), age (HR 1.21, 95% CI 1.06–1.38, P = 0.004), and baseline glucose level (HR 1.11, 95% CI 1.06–1.15, P < 0.001) to be independent predictors for occurrence of new DM. High-sensitivity CRP was an independent factor for future development of DM in essential hypertensive patients. Increased inflammation might have a key role in the pathogenesis of DM in hypertension.