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1.  Organic Nitrates Favor Regression of Left Ventricular Hypertrophy in Hypertensive Patients on Chronic Peritoneal Dialysis 
The aim of the study was to evaluate the effect of nitrates on left ventricular hypertrophy (LVH) in hypertensive patients on chronic peritoneal dialysis (PD). Sixty-four PD patients with hypertension were enrolled in this study. All patients accepted antihypertensive drugs at baseline. Thirty-two patients (nitrate group) took isosorbide mononitrate for 24 weeks. The remaining 32 patients (non-nitrate group) took other antihypertensive drugs. Blood pressure (BP), left ventricular mass index (LVMI) and plasma asymmetric dimethylarginine (ADMA) were monitored. Subjects with normal renal function were included as the control group (n = 30). At baseline, plasma ADMA levels in PD patients were significantly higher than the control group, but there was no significant difference in plasma ADMA levels between the two groups. At the end of the 24-week period, BP, LVMI, LVH prevalence and plasma ADMA levels in the nitrate group were significantly lower than those in the non-nitrate group. BP did not show a significant difference between 12 and 24 weeks in the nitrate group with a reduced need for other medication. Logistic regression analysis showed that nitrate supplementation and SBP reduction were independent risk factors of LVMI change in PD patients after adjusting for age, gender, diabetes history and CCB supplementation. It was concluded that organic nitrates favor regression of LVH in hypertensive patients on chronic peritoneal dialysis, and nitrates may be considered for use before employing the five other antihypertensive agents other than nitrates.
PMCID: PMC3565307  PMID: 23296279
nitrate; ADMA; hypertension; left ventricular hypertrophy; renal dialysis
2.  Effects of Azelnidipine plus OlmesaRTAn versus amlodipine plus olmesartan on central blood pressure and left ventricular mass index: the AORTA study 
The aim of this study was to compare the effects of olmesartan combined with either azelnidipine or amlodipine on central blood pressure (CBP) and left ventricular mass index (LVMI) in hypertensive patients.
Patient and methods:
Patients with brachial systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg received olmesartan monotherapy (20 mg daily) for 12 weeks. The patients were then randomly assigned to fixed-dose add-on therapy with azelnidipine (16 mg daily) or amlodipine (5 mg daily) (25 patients/group) for a further 24 weeks. CBP and LVMI were measured at baseline and at the end of the study.
Baseline characteristics were similar in both groups. The decrease in brachial BP was similar in both groups. CBP and LVMI decreased significantly in both groups (both, P < 0.001). However, the decreases in CBP and LVMI were significantly greater with olmesartan/azelnidipine than with olmesartan/amlodipine (CBP, P < 0.001; LVMI, P = 0.002).
These findings indicate that olmesartan/azelnidipine had greater effects on CBP and LVMI than did olmesartan/amlodipine, even though the reduction in brachial BP was similar in both groups. These differential effects on CBP and LVMI may have important implications for cardiovascular risk reduction.
PMCID: PMC3141910  PMID: 21796252
central blood pressure; left ventricular mass index; augmentation index; brachial-ankle pulse wave velocity; olmesartan/azelnidipine
3.  Endothelial dysfunction is associated with left ventricular mass (assessed using MRI) in an adult population (MESA) 
Journal of human hypertension  2010;25(1):25-31.
Brachial flow-mediated dilation (FMD) is a measure of endothelial nitric oxide bioavailability. Endothelial nitric oxide controls vascular tone and is likely to modify the ventricular muscle coupling mechanism. The association between left ventricular mass and FMD is not well understood. We assessed the association between left ventricular mass index (LVMI) and FMD in participants of the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a population-based study of 6814 adults free of clinical cardiovascular disease at baseline who were recruited from six US clinics. LVMI (left ventricular mass per body surface area) and FMD were measured in 2447 subjects. Linear regression analysis was used to evaluate the association. The subjects had a mean age of 61.2 ± 9.9 years, 51.2% females with 34.3% Caucasians, 21.6% Chinese, 19.4% African Americans and 24.7% Hispanics. The mean body mass index (BMI) was 27.4 ± 4.8 kg m−2, 9.4% had diabetes, 11% were current smokers and 38% hypertensives. The mean ± s.d. LVMI was 78.1 ± 15.9 g m−2 and mean ± s.d. FMD was 4.4% ± 2.8%. In univariate analysis, LVMI was inversely correlated with FMD (r = −0.20, P < 0.0001). In the multivariable analysis, LVMI was associated with FMD (β coefficient (se) = −0.50 (0.11), P < 0.001 (0.5 g m−2 reduction in LVMI per 1% increase in FMD)) after adjusting for age, gender, race/ethnicity, systolic blood pressure, diabetes mellitus, smoking, weight, statin use, antihypertensive medication use, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol. The association between brachial flow mediated dilation and LVMI maybe independent of traditional CV risk factors in population based adults.
PMCID: PMC3037860  PMID: 20237502
left ventricular mass; endothelial function; brachial flow-mediated dilation; population
4.  Body mass index-mortality paradox in hemodialysis: can it be explained by blood pressure? 
Hypertension  2011;58(6):1014-1020.
Unlike the general population, among hemodialysis patients body-mass index(BMI)is inversely related to blood pressure (BP) and mortality. To explore the reasons for this risk-factor paradox the cross-sectional association of obesity with the following factors was examined: the prevalence of hypertension, its control and echocardiographic left ventricular mass index (LVMI). Longitudinal follow-up explored the relationship of BMI with all-cause mortality. Further it explored whether poorer survival in leaner individuals was related to either high BP or greater LVMI. Among 368 hemodialysis patients both the prevalence of hypertension and its poor control were inversely related to BMI. BMI was also inversely associated with evidence of excess extracellular fluid volume but adjustment for this variable did not completely remove the inverse relationship between BP and BMI. Over 1122 patient-years of cumulative follow up (median 2.7 years) 119 (32%) patients died. In the first two years of follow up, the mortality hazard for the lowest BMI group was increased; thereafter, the survival curves were similar. Adjusting for several risk factors including BP and LVMI did not remove the inverse relationship of BMI with mortality. In conclusion, leaner patients on dialysis have a higher prevalence of hypertension, poorer control of hypertension, more LVMI, and greater evidence of extracellular fluid volume excess. However, volume only partially explains the greater prevalence or poorer control of hypertension. Leaner patients have an accelerated mortality rate in the first two years; this is not completely explained by BP, LVMI or other cardiovascular or dialysis-specific risk factors.
PMCID: PMC3241970  PMID: 22042814
Body mass index; epidemiology; hemodialysis; ambulatory blood pressure; left ventricular hypertrophy; survival
5.  Reduced global longitudinal strain in association to increased left ventricular mass in patients with aortic valve stenosis and normal ejection fraction: a hybrid study combining echocardiography and magnetic resonance imaging 
Increased muscle mass index of the left ventricle (LVMi) is an independent predictor for the development of symptoms in patients with asymptomatic aortic stenosis (AS). While the onset of clinical symptoms and left ventricular systolic dysfunction determines a poor prognosis, the standard echocardiographic evaluation of LV dysfunction, only based on measurements of the LV ejection fraction (EF), may be insufficient for an early assessment of imminent heart failure. Contrary, 2-dimensional speckle tracking (2DS) seems to be superior in detecting subtle changes in myocardial function. The aim of the study was to assess these LV function deteriorations with global longitudinal strain (GLS) analysis and the relations to LVMi in patients with AS and normal EF.
50 patients with moderate to severe AS and 31 controls were enrolled. All patients underwent echocardiography, including 2DS imaging. LVMi measures were performed with magnetic resonance imaging in 38 patients with AS and indexed for body surface area.
The total group of patients with AST showed a GLS of -15,2 ± 3,6% while the control group reached -19,5 ± 2,7% (p < 0,001). By splitting the group with AS in normal, moderate and severe increased LVMi, the GLS was -17,0 ± 2,6%, -13,2 ± 3,8% and -12,4 ± 2,9%, respectively (p = 0,001), where LVMi and GLS showed a significant correlation (r = 0,6, p < 0,001).
In conclusion, increased LVMi is reflected in abnormalities of GLS and the proportion of GLS impairment depends on the extent of LV hypertrophy. Therefore, simultaneous measurement of LVMi and GLS might be useful to identify patients at high risk for transition into heart failure who would benefit from aortic valve replacement irrespectively of LV EF.
PMCID: PMC2923627  PMID: 20659321
6.  Effects of Verapamil Slow Release Plus Trandolapril Combination Therapy on Essential Hypertension 
Background: Fixed-dose combination antihypertensive therapy has been recommended for patients with essential hypertension who are unresponsive to monotherapy or as a first-line treatment.
Objective: We investigated the effects of a fixed-dose combination of the phenylalkylamine-type calcium channel blocker verapamil slow release (SR)plus the angiotensin-converting enzyme inhibitor trandolapril on blood pressure (BP), serum lipid profile, urinary albumin excretion (UAE), left ventricular mass (LVM), and LVM index (LVMI), as well as the adverse events associated with this treatment.
Methods: Patients aged 30 to 65 years with mild to moderate essential hypertension were included in the study. All of the patients received capsules containing combination treatment with verapamil SR 180 mg plus trandolapril 2 mg orally, daily for 12 weeks. Mean arterial pressure (MAP), systolic BP (SBP), diastolic BP (DBP), and heart rate (HR) were measured at baseline and at 4, 8, and 12 weeks of treatment. Serum lipid profile, UAE, LVM, LVMI, and body mass index (BMI) were determined at baseline and at the end of the study period. All patients underwent electrocardiography and echocardiography at baseline and week 12. The primary end point of the study was to achieve an SBP/DBP ≤140/≤90 mm Hg (ie, normotensive) during week 12. All adverse events were assessed as mild, moderate, or severe at each visit. According to the response rate at week 12, patients were divided into 2 groups: those who became normotensive (responders) or those who remained hypertensive (SBP/DBP >140/>90 mm Hg; nonresponders).
Results: Forty-one patients (29 women, 12 men; mean [SD] age, 47.7 [7.8] years; mean [SD] BMI, 29.4 [3.5] kg/m2) were enrolled. The median durationof hypertension prior to enrollment was 5 months. Mean MAP, SBP, DBP, UAE, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), LDL-C/highdensity lipoprotein cholesterol (HDL-C) ratio, LVM, LVMI, and BMI decreased significantly after 12 weeks of combination treatment; HR and triglyceride level did not change significantly. Treatment-related adverse events occurred in 31.7% of patients, and none were severe or caused any patient to withdraw from the study. The most common adverse events were cough, constipation, headache, and dryness in the throat. Microalbuminuria, which may be a marker of endothelial dysfunction, was found in 7 (17.1%) patients at baseline and regressed significantly after 12 weeks.
Conclusions: In this study population, the fixed-dose combination of verapamil–trandolapril was an effective and well-tolerated antihypertensive therapy. This combination significantly reduced MAP, BP, TC, LDL-C, LDL-C/HDL-C ratio, UAE, LVM, and LVMI. Also, microalbuminuria decreased after this treatment. Verapamil–trandolapril may be useful in preventing microalbuminuria and left ventricular hypertrophy in patients with essential hypertension.
PMCID: PMC4053024  PMID: 24944353
essential hypertension; combination therapy; trandolapril; verapamil
7.  Shorter delivered dialysis times associate with a higher and more difficult to treat blood pressure 
Nephrology Dialysis Transplantation  2013;28(6):1562-1568.
Shorter delivered dialysis times are associated with increased all-cause mortality. Whether shorter delivered dialysis times also associate with an increase in blood pressure (BP) and reduce the ability of probing dry weight to lower BP is unclear.
Among patients participating in the Dry-Weight Reduction in Hypertensive Hemodialysis Patients (DRIP) trial, interdialytic ambulatory BP was recorded at baseline, 4 weeks and 8 weeks. Median intradialytic BP was also calculated at each dialysis treatment and associated with the delivered daily dialysis time.
The median time on dialysis at baseline was 3.6 h per treatment (range 2.5–4.5 h). At baseline, modeled median intradialytic systolic BPs were higher among those who received fewer hours of dialysis. Among subjects who did not have their dry weight probed (control group), the median intradialytic systolic BP continued to be elevated. Probing dry weight (ultrafiltration group) provoked a drop in median intradialytic systolic BP regardless of the delivered dialysis time. However, the reduction in BP was achieved after fewer sessions of dialysis when delivered dialysis was longer in duration. The pattern of change was confirmed using interdialytic ambulatory BP monitoring.
Fewer hours of delivered dialysis are associated with a higher systolic BP. Upon probing dry weight, compared with shorter dialysis treatment times, 4 h of delivered dialysis per session provokes reductions in systolic BP over fewer dialysis treatment sessions. Reduction of BP may lag dry-weight reduction when shorter dialysis is delivered.
PMCID: PMC3685306  PMID: 23348881
hemodialysis; hypertension
8.  The Relationship between Adiponectin and Left Ventricular Mass Index Varies with the Risk of Left Ventricular Hypertrophy 
PLoS ONE  2013;8(7):e70246.
Adiponectin directly protects against cardiac remodeling. Despite this beneficial effect, most epidemiological studies have reported a negative relationship between adiponectin level and left ventricular mass index (LVMI). However, a positive relationship has also been reported in subjects at high risk of left ventricular hypertrophy (LVH). Based on these conflicting results, we hypothesized that the relationship between serum adiponectin level and LVMI varies with the risk of LVH.
A community-based, cross-sectional study was performed on 1414 subjects. LVMI was measured by echocardiography. Log-transformed adiponectin levels (Log-ADPN) were used for the analysis.
Serum adiponectin level had a biphasic distribution (an increase after a decrease) with increasing LVMI. Although Log-ADPN did not correlate with LVMI, Log-ADPN was modestly associated with LVMI in the multivariate analysis (β = 0.079, p = 0.001). The relationship between adiponectin level and LVMI was bidirectional according to the risk of LVH. In normotensive subjects younger than 50 years, Log-ADPN negatively correlated with LVMI (r = −0.204, p = 0.005); however, Log-ADPN positively correlated with LVMI in ≥50-year-old obese subjects with high arterial stiffness (r = 0.189, p = 0.030). The correlation coefficient between Log-ADPN and LVMI gradually changed from negative to positive with increasing risk factors for LVH. The risk of LVH significantly interacted with the relationship between Log-ADPN and LVMI. In the multivariate analysis, Log-ADPN was associated with LVMI in the subjects at risk of LVH; however, Log-ADPN was either not associated or negatively associated with LVMI in subjects at low risk of LVH.
Adiponectin level and LVMI are negatively associated in subjects at low risk of LVH and are positively associated in subjects at high risk of LVH. Therefore, the relationship between adiponectin and LVMI varies with the risk of LVH.
PMCID: PMC3722139  PMID: 23894624
9.  Parallel improvement of left ventricular geometry and filling pressure after transcatheter aortic valve implantation in high risk aortic stenosis: comparison with major prosthetic surgery by standard echo Doppler evaluation 
The effect of Transcatheter Aortic Valve Implantation (TAVI) on left ventricular (LV) geometry and function was compared to traditional aortic replacement (AVR) by major surgery.
45 patients with aortic stenosis (AS) undergoing TAVI and 33 AVR were assessed by standard echo Doppler the day before and 2 months after the implantation. 2D echocardiograms were performed to measure left ventricular (LV) mass index (LVMi), relative wall thickness (RWT), ejection fraction (EF) and the ratio between transmitral E velocity and early diastolic velocity of mitral annulus (E/e’ ratio). Valvular-arterial impedance (Zva) was also calculated.
At baseline, the 2 groups were comparable for blood pressure, heart rate, body mass index mean transvalvular gradient and aortic valve area. TAVI patients were older (p<0.0001) and had greater LVMi (p<0.005) than AVR group. After 2 months, both the procedures induced a significant reduction of transvalvular gradient and Zva but the decrease of LVMi and RWT was significant greater after TAVI (both p<0.0001). E/e’ ratio and EF were significantly improved after both the procedure but E/e’ reduction was greater after TAVI (p<0.0001). TAVI exhibited greater percent reduction in mean transvalvular gradient (p<0.05), Zva (p<0.02), LVMi (p<0.0001), RWT (p<0.0001) and E/e’ ratio (p<0.0001) than AVR patients. Reduction of E/e’ ratio was positively related with reduction of RWT (r = 0.46, p<0.002) only in TAVI group, even after adjusting for age and percent reduction of Zva (r =0.43, p<0.005).
TAVI induces a greater improvement of estimated LV filling pressure in comparison with major prosthetic surgery, due to more pronounced recovery of LV geometry, independent on age and changes of hemodynamic load.
PMCID: PMC3679950  PMID: 23731705
Transcatheter aAortic valve implantation; Doppler echocardiography; Relative wall thickness; Left ventricular mass
10.  Telmisartan Versus Valsartan in Patients With Hypertension: Effects on Cardiovascular, Metabolic, and Inflammatory Parameters 
Korean Circulation Journal  2011;41(10):583-589.
Background and Objectives
Angiotensin-receptor blockers (ARBs) have beneficial effects on cardiovascular, metabolic, and inflammatory parameters in addition to controlling blood pressure (BP). However, few comparative clinical studies have been conducted with different ARBs. We compared these effects in patients with uncomplicated hypertension who were receiving telmisartan or valsartan.
Subjects and Methods
The subjects were patients with essential hypertension (48.4±9.6 years) who were randomly assigned to take either telmisartan (80 mg/day, n=30) or valsartan (160 mg/day, n=30) for 12 weeks. Their anthropometric, laboratory, vascular, and echocardiographic data were measured at baseline and at the end of the study.
Baseline characteristics were not significantly different between the two groups, except for the carotid-femoral pulse wave velocity (cfPWV; telmisartan group vs. valsartan group; 841.2±131.0 vs. 761.1±104.4 cm/s, p<0.05). After 12 weeks, BP had fallen to a similar extent with mean reductions in the systolic and diastolic BP of 20.7±18.1 and 16.3±13.0 mm Hg (p<0.001, respectively) for the telmisartan and 22.5±17.0 and 16.8±9.3 mm Hg (p<0.001, respectively) for the valsartan group. Although the cfPWV and left ventricular mass index (LVMI) fell significantly only with the administration of telmisartan, they were not significantly different when baseline cfPWV was considered. The differences in the cfPWV and LVMI changes from baseline between the two groups were also not significant after adjusting for baseline cfPWV. No significant changes in other vascular, metabolic, or inflammatory parameters were observed with either treatment.
The effects of a 12-week treatment with the two ARBs, telmisartan and valsartan, on cardiovascular, metabolic, and inflammatory parameters were not different in patients with uncomplicated hypertension.
PMCID: PMC3221900  PMID: 22125557
Hypertension; Valsartan
11.  Effect of Frequent or Extended Hemodialysis on Cardiovascular Parameters: A Meta-analysis 
Increased left ventricular (LV) mass is a risk factor for cardiovascular mortality in patients with chronic kidney failure. More frequent or extended hemodialysis (HD) has been hypothesized to have a beneficial effect on LV mass.
Study Design
Setting & Population
MEDLINE literature search (inception-April 2011), Cochrane Central Register of Controlled Trials and using the search terms “short daily HD”, “daily HD”, “quotidian HD”, “frequent HD”, “intensive HD”, “nocturnal HD”, and “home HD”.
Selection Criteria for Studies
Single-arm cohort studies (with pre- and post-study evaluations) and randomized controlled trials examining the effect of frequent or extended HD on cardiac morphology and function, and blood pressure parameters. Studies of hemofiltration, hemodiafiltration and peritoneal dialysis were excluded.
Frequent (2–8 hours,> thrice weekly) or extended (>4 hours, thrice weekly) HD as compared with conventional (≤ 4 hours, thrice weekly) HD.
Absolute changes in cardiac morphology and function, including LV mass index (LVMI) (primary), and blood pressure parameters (secondary).
We identified 38 single-arm studies, 5 crossover trials and 3 randomized controlled trials. By meta-analysis of 23 study arms, frequent or extended HD significantly reduced LVMI from baseline (−31.2 g/m2, 95% CI, −39.8 to −22.5; P<0.001).The 3 randomized trials found a less pronounced net reduction in LVMI (−7.0 g/m2; 95% CI, −10.2 to −3.7; P<0.001). LV ejection fraction improved by 6.7% (95% CI, 1.6 to 11.9; P=0.01). Other cardiac morphological parameters displayed similar improvements. There were also significant decreases in systolic, diastolic, and mean blood pressure, and mean number of anti-hypertensive medications.
Paucity of randomized controlled trials.
Conversion from conventional to frequent or extended HD is associated with an improvement in cardiac morphology and function, including LVMI and LV ejection fraction, respectively, and in several blood pressure parameters, which collectively might confer long-term cardiovascular benefit. Trials with long-term clinical outcomes are needed.
PMCID: PMC3395217  PMID: 22370022
frequent HD; extended HD; conventional HD; LVMI; meta-analysis
12.  Hypertension and hyperparathyroidism are associated with left ventricular hypertrophy in patients on hemodialysis 
Indian Journal of Nephrology  2009;19(4):153-157.
Conflicting data for association between left ventricular hypertrophy (LVH) and secondary hyperparathyroidism has been reported previously among dialysis patients. The present study was conducted to evaluate the association of hyperparathyroidism and hypertension with LVH. Charts of 130 patients on hemodialysis for at least six months were reviewed. All were subjected to M-mode echocardiography. Left ventricular mass (LVM) was calculated by Devereux's formula. LVM Index (LVMI) was calculated by dividing LVM by body surface area. Sera were analyzed for intact parathyroid hormone (iPTH). iPTH of > 32 pmol/l and a mean blood pressure (MAP) of > 107 mmHg were considered high. Patients were stratified into groups according to their MAP and iPTH. A total of (47.7%) patients were males and 68 (52.3%) were females. Their median age was 57 years. The median duration on dialysis was 26 months. Forty eight (36.9%) patients had high BP and 54 (41.5%) had high iPTH. Both high BP and high iPTH were present in 38 (29.2%) patients. Analysis of the relationship between LVM, LVMI, MAP and iPTH showed that LVM and LVMI were significantly (P < 0.001) higher in patients with concomitant high BP and high iPTH. LVMI was significantly higher in patients with high iPTH alone. Concomitant high iPTH and high MAP increase the risk of LVH in hemodialysis patients. High iPTH alone might contribute in escalating LVH. Adequate control of hypertension and hyperparathyroidism might reduce the risk of developing LVH.
PMCID: PMC2875705  PMID: 20535251
Hemodialysis; hypertension; hyperparathyroidism; left ventricular hypertrophy
13.  Left ventricular mass index in children with white coat hypertension 
The Journal of pediatrics  2008;153(1):50-54.
To determine if children with white coat hypertension (WCH) have evidence of target-organ damage by comparing left ventricular mass index (LVMI) of subjects with WCH to that of matched normotensive and hypertensive controls.
Study design
Each WCH subject was matched by body mass index (± 10%), age (± 1 year), and sex to a normotensive control and to a hypertensive control. Echocardiograms were reviewed to determine LVMI for each subject. These triple matches were analyzed using repeated measures analysis of variance to detect differences in LVMI between the three groups.
Twenty-seven matched triplets were established. The groups were comparable for sex, age, and body mass index (BMI). Mean LVMI was 29.2, 32.3, and 35.1 g/m2.7, for normotensives, WCH, and sustained hypertensives, respectively (normotensive vs. WCH, p = 0.028; WCH vs. sustained hypertensive, p = 0.07). Left ventricular hypertrophy was not present in any subject in the normotensive or WCH groups, but was present in 26% of the sustained hypertensive subjects (p < 0.001).
After controlling closely for BMI, children with WCH had a LVMI which was intermediate between that of normotensives and sustained hypertensives, suggesting that WCH may be associated with hypertensive end-organ effects.
PMCID: PMC2516747  PMID: 18571535
14.  L/N-Type Calcium Channel Blocker Cilnidipine Added to Renin-Angiotensin Inhibition Improves Ambulatory Blood Pressure Profile and Suppresses Cardiac Hypertrophy in Hypertension with Chronic Kidney Disease 
Ambulatory blood pressure (BP) and heart rate (HR) profile are proposed to be related to renal deterioration and cardiovascular complication in hypertension and chronic kidney disease (CKD). In this study, we examined the beneficial effects cilnidipine, a unique L/N-type calcium channel blocker (CCB), in addition to renin-angiotensin system inhibitors, on ambulatory BP and HR profile, as well as cardiorenal function in hypertensive CKD patients. Forty-five patients were randomly assigned to the cilnidipine replacement group (n = 21) or the control CCBs group (n = 24) during a 24-week active treatment period. Although clinical BP values were similar in the cilnidipine and control CCBs groups after the treatment period, the results of ambulatory BP monitoring showed that the 24-h and daytime systolic BP levels in the cilnidipine group were significantly lower compared with the control group after the study. Furthermore, the left ventricular mass index (LVMI) was significantly decreased in the cilnidipine group compared to the control group after the study (LVMI, 135.3 ± 26.4 versus 181.2 ± 88.4, p = 0.031), with a significant difference in the changes in the LVMI between the cilnidipine and control groups (change in LVMI, −12.4 ± 23.7 versus 26.2 ± 64.4, p = 0.007). These results indicate that cilnidipine is beneficial for the suppression of pathological cardiac remodeling, at least partly, via a superior improving effect on ambulatory BP profile compared with control CCBs in hypertensive CKD patients.
PMCID: PMC3759940  PMID: 23959116
ambulatory blood pressure; calcium channel blockers; cardiac hypertrophy; chronic kidney disease; heart rate variability; hypertension (kidney)
15.  Intradialytic hypertension is a marker of volume excess 
Nephrology Dialysis Transplantation  2010;25(10):3355-3361.
Background. Intradialytic blood pressure (BP) profiles have been associated with all-cause mortality, but its pathophysiology remains unknown. We tested the hypothesis that intradialytic changes in BP reflect excess volume.
Methods. The dry weight reduction in hypertensive haemodialysis patients (DRIP) trial probed dry weight in 100 prevalent haemodialysis patients; 50 patients who did not have their dry weight probed served as time controls. In this post hoc analysis, intradialytic BP was recorded at each of the 30 dialysis treatments during the trial. The slope of intradialytic BP over dialysis was calculated by the log of BP regressed over time. Using a linear mixed model, we compared these slopes between control and ultrafiltration groups at baseline and over time, tested the effect of dry weight reduction on these slopes and finally tested the ability of change in intradialytic slopes to predict change in interdialytic systolic BP.
Results. At baseline, intradialytic systolic and diastolic BP dropped at a rate of ~3%/h (P < 0.0001). Over the course of the trial, compared to the control group, the slopes steepened in the ultrafiltration group for systolic but not diastolic BP. Those who lost the most post-dialysis weight from baseline to 4 weeks and baseline to 8 weeks also experienced the greatest steepening of slopes. Each percent per hour steepening of the intradialytic systolic BP slope was associated with 0.71 mmHg [95% confidence interval (CI) 0.01–1.42, P = 0. 048] reduction in interdialytic ambulatory systolic pressure.
Conclusions. Intradialytic BP changes appear to be associated with change in dry weight among haemodialysis patients. Among long-term haemodialysis patients, intradialytic hypertension may, thus, be a sign of volume overload.
PMCID: PMC2948838  PMID: 20400448
ambulatory BP; dry weight; haemodialysis; hypertension; sodium
16.  The Relationship Between Metabolic Syndrome and Left Ventricular Mass Index in Obese Children  
Objective: To investigate the relationships between metabolic syndrome (MS), other metabolic features and left ventricular mass index (LVMI) in a population of obese children and adolescents with MS.
Methods: Two hundred and eight obese children and adolescents (119 females and 89 males, mean age: 11.9±2.7 years) and control subjects (24 females and 26 males, mean age: 11.4±2.9 years) were enrolled in the study. The insulin sensitivity index and LVMI were determined. The International Diabetes Federation criteria were used to diagnose MS.
Results: The obese patients were divided into MS group (n=55) and non-MS (n=153) group. The values of LVMI in the MS group were significantly higher than those in the non-MS group (p=0.014). The present LVMI cut-off point of 33g/m2 for the diagnosis of MS yielded a sensitivity of 97% and a specificity of 98%. LVMI was found to be positively correlated in univariate analysis with height, weight, body mass index (BMI) SDS, fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) and fasting glucose to insulin ratio (FGIR) and negatively correlated with quantitative insulin sensitivity check index (QUICK-I).
Conclusions: We suggest that our optimal LVMI cut-off value for identifying MS may be considered as a sensitive index in screening obese children and adolescents for pediatric MS. Assessment of LVMI in obese children and adolescents may be used as a tool in predicting the presence of MS and its associated cardiovascular risks.
Conflict of interest:None declared.
PMCID: PMC3184514  PMID: 21911326
obesity; metabolic syndrome; cardiovascular disease; left ventricular mass index; children
17.  Midlife blood pressure change and left ventricular mass and remodelling in older age in the 1946 British birth cohort study† 
European Heart Journal  2014;35(46):3287-3295.
Antecedent blood pressure (BP) may contribute to cardiovascular disease (CVD) independent of current BP. Blood pressure is associated with left ventricular mass index (LVMI) which independently predicts CVD. We investigated the relationship between midlife BP from age 36 to 64 and LVMI at 60–64 years.
Methods and results
A total of 1653 participants in the British 1946 Birth Cohort underwent BP measurement and echocardiography aged 60–64. Blood pressure had previously been measured at 36, 43, and 53 years. We investigated associations between BP at each age and rate of change in systolic blood pressure (SBP) between 36–43, 43–53, and 53–60/64 years on LVMI at 60–64 years. Blood pressure from 36 years was positively associated with LVMI. Association with SBP at 53 years was independent of SBP at 60–64 years and other potential confounders (fully adjusted β at 53 years = 0.19 g/m2; 95% CI: 0.11, 0.27; P < 0.001). Faster rates of increase in SBP from 43 to 53 years and 53 to 60/64 years were associated with increased LVMI. Similar relationships were seen for diastolic, pulse, and mean pressure. Rate of increase in SBP between 43–53 years was associated with largest change in LVMI (β at 43–53 years = 3.12 g/m2; 95% CI: 1.53, 4.72; P < 0.001). People on antihypertensive medication (43 years onwards) had greater LVMI even after adjustment for current BP (β at 43 years = 12.36 g/m2; 95% CI: 3.19, 21.53; P = 0.008).
Higher BP in midlife and rapid rise of SBP in 5th decade is associated with higher LVMI in later life, independent of current BP. People with treated hypertension have higher LVMI than untreated individuals, even accounting for their higher BP. Our findings emphasize importance of midlife BP as risk factor for future CVD.
PMCID: PMC4258225  PMID: 25246483
Blood pressure; Left ventricular mass; Left ventricular hypertrophy; Echocardiography
18.  Effect of tanshinone IIA on cardiomyocyte hypertrophy and apoptosis in spontaneously hypertensive rats 
In the present study, the effects of tanshinone IIA (TSN) on the prevention of left ventricular hypertrophy (LVH) and apoptotic processes were observed in spontaneously hypertensive rats (SHRs). A total of 18 SHRs (age, 8 weeks) were randomly divided into three groups. The SHRs in the control group (group S8) were sacrificed at week 8 of the experiment. The SHRs in the treatment group (group D18) and the placebo group (group S18) were injected with TSN and distilled water (1 ml/kg body weight/day), respectively, for 10 weeks, commencing at week 8, and were subsequently sacrificed at week 18. The systolic blood pressure (SBP) and left ventricular mass index (LVMI) were determined. Using hematoxylin and eosin and van Gieson staining, together with immunohistological methods, cardiomyocyte size and diameter, collagen volume fraction (CVF) and perivascular circumferential area (PVCA) were measured. Evaluation of Bcl-2, Bax and p53 expression levels for apoptosis analysis was performed using western blotting. It was observed that the SBP, LVMI, cardiomyocyte size and diameter, CVF, PCVA and cardiomyocyte apoptosis index (Bax and p53 expression) were increased significantly in group S18 compared with group S8. However, Bcl-2 expression levels were decreased in group S18 compared with group S8. The administration of TSN in group D18 resulted in higher Bcl-2 expression levels and significantly decreased LVMI, cardiomyocyte size and diameter, CVF, PCVA, Bax and p53 expression levels compared with group S18. LVH and apoptosis of the cardiac tissues increased with the increasing age of the SHRs. TSN may inhibit the development of LVH and decrease the level of apoptosis in SHRs, possibly via the upregulation of Bcl-2 and the downregulation of Bax and p53 expression.
PMCID: PMC3829736  PMID: 24255684
left ventricular hypertrophy; apoptosis; tanshinone IIA; p53; Bcl-2; Bax
19.  Cardiac and vascular structure and function parameters do not improve with alternate nightly home hemodialysis: An interventional cohort study 
BMC Nephrology  2011;12:51.
Nightly extended hours hemodialysis may improve left ventricular hypertrophy and function and endothelial function but presents problems of sustainability and increased cost. The effect of alternate nightly home hemodialysis (NHD) on cardiovascular structure and function is not known.
Sixty-three patients on standard hemodialysis (SHD: 3.5-6 hours/session, 3-5 sessions weekly) converted to NHD (6-10 hours/session overnight for 3-5 sessions weekly). 2Dimensional transthoracic echocardiography and ultrasound measures of brachial artery reactivity (BAR), carotid intima-media thickness (CIMT), total arterial compliance (TAC) and augmentation index (AIX) were performed post dialysis at baseline and 18-24 months following conversion to NHD. In 37 patients, indices of oxidative stress: plasma malonyldialdehyde (MDA) and anti-oxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD) activity and total antioxidant status (TAS) were measured at baseline, 3 and 6 months.
Left ventricular mass index (LVMI) remained stable. Despite significant derangement at baseline, there were no changes in diastolic function measures, CIMT, BAR and TAC. AIX increased. Conversion to NHD improved bone mineral metabolism parameters and blood pressure control. Interdialytic weight gains increased. No definite improvements in measures of oxidative stress were demonstrated.
Despite improvement in uremic toxin levels and some cardiovascular risk factors, conversion to an alternate nightly NHD regimen did not improve cardiovascular structure and function. Continuing suboptimal control of uremic toxins and interdialytic weight gains may be a possible explanation. This study adds to the increasing uncertainty about the nature of improvement in cardiovascular parameters with conversion to intensive hemodialysis regimens. Future randomized controlled trials will be important to determine whether increases in dialysis session duration, frequency or both are most beneficial for improving cardiovascular disease whilst minimizing costs and the impact of dialysis on quality of life.
PMCID: PMC3202231  PMID: 21962236
Diastolic Function; Ejection Fraction; Left Ventricular Mass Index; Left Ventricular Hypertrophy; Nocturnal Hemodialysis; Carotid Intima-Media Thickness; Oxidative Stress; Arterial Compliance
20.  Hyperglycemia and nocturnal systolic blood pressure are associatedwith left ventricular hypertrophy and diastolic dysfunction in hypertensive diabetic patients 
The aim of this study was to determine if hypertensive type 2 diabetic patients, when compared to patients with essential hypertension have an increased left ventricular mass index (LVMI) and a worse diastolic function, and if this fact would be related to 24-h pressoric levels changes.
Ninety-one hypertensive patients with type 2 diabetes mellitus (DM) (group-1 [G1]), 59 essential hypertensive patients (group-2 [G2]) and 26 healthy controls (group-3 [G3]) were submitted to 24-h Ambulatory Blood Pressure Monitoring (ABPM) and echocardiography (ECHO) with Doppler. We calculated an average of fasting blood glucose (AFBG) values of G1 from the previous 4.2 years and a glycemic control index (GCI) (percentual of FBG above 200 mg/dl).
G1 and G2 did not differ on average of diurnal systolic and diastolic BP. However, G1 presented worse diastolic function and a higher average of nocturnal systolic BP (NSBP) and LVMI (NSBP = 132 ± 18 vs 124 ± 14 mmHg; P < 0.05 and LVMI = 103 ± 27 vs 89 ± 17 g/m2; P < 0.05, respectively). In G1, LVMI correlated with NSBP (r = 0.37; P < 0.001) and GCI (r = 0.29; P < 0.05) while NSBP correlated with GCI (r = 0.27; P < 0.05) and AFBG (r = 0.30; P < 0.01). When G1 was divided in tertiles according to NSBP, the subgroup with NSBP≥140 mmHg showed a higher risk of LVH. Diabetics with NSBP≥140 mmHg and AFBG>165 mg/dl showed an additional risk of LVH (P < 0.05; odds ratio = 11). In multivariate regression, both GCI and NSBP were independent predictors of LVMI in G1.
This study suggests that hyperglycemia and higher NSBP levels should be responsible for an increased prevalence of LVH in hypertensive patients with Type 2 DM.
PMCID: PMC1579206  PMID: 16968545
21.  Use of Cardiac Magnetic Resonance Imaging to Evaluate Cardiac Structure, Function and Fibrosis in Children with Infantile Pompe Disease on Enzyme Replacement Therapy 
Molecular genetics and metabolism  2010;101(4):332-337.
Pompe disease (acid α-glucosidase deficiency) is one of several lysosomal storage diseases amenable to treatment with enzyme replacement therapy (ERT). While echocardiography (echo) has been the standard method to evaluate the cardiac response to ERT, cardiac magnetic resonance imaging (CMR) has the advantage of better tissue definition and characterization of myocardial fibrosis. However, CMR for Pompe disease is not frequently performed due to the high risk of sedation. We report the first use of CMR in a feasible protocol to quantify left ventricular (LV) mass, function, and presence of myocardial fibrosis in the Pompe population.
Children with Pompe disease on ERT were assessed with transthoracic echo and CMR over a 3 year period at a single institution. Echocardiography was performed using standard techniques without sedation. CMR was performed using retrospectively gated and real-time imaging, with and without sedation. LV mass indexed to body surface area (LVMI) and ejection fraction (EF) were measured by both echo and CMR, and evaluated for change over time. Myocardial fibrosis was assessed with CMR by delayed enhancement imaging 5-10 min after gadolinium contrast using single-shot inversion recovery sequences with inversion time set to null the myocardium.
Seventeen CMR scans were successfully performed in 10 subjects with Pompe disease (median age at first CMR 9 months, range 1-38 months, 80% male), with sedation only performed for 4 studies. There was a median interval of 5 months (range 0-34 months) from start of ERT to first CMR (baseline). At baseline, median indexed LVMI by CMR (140.0 g/m2, range 43.8-334.0) tended to be lower than that assessed by echo (median 204.0 g/m2, range 52.0-385.0), but did not reach statistical significance. At baseline, CMR EF was similar to that assessed by echo (55% vs. 55%). Overall, there was not a significant decrease in CMR measured LVMI over time (CMR median LVMI at baseline 94 g/m2 (range 43.8-334) vs. CMR median at most recent study 44.5 g/m2 (range 34-303), p=0.44). In 5 patients with serial CMR scans over time, LVMI decreased in 2, was similar in 2, and increased in 1 patient with high sustained antibodies to exogenous enzyme. Delayed enhancement was noted in only l separate patient who also had high sustained antibodies to exogenous enzyme.
CMR is a useful imaging tool that is feasible to use to serially follow LVMI and EF in children with Pompe disease on ERT. Real-time imaging is adequate for quantification purposes in these patients and minimizes the need for sedation. Quantitative CMR LVMI is generally lower than echo derived LVMI. Delayed enhancement appears to be a rare finding by CMR in Pompe Disease. Further follow-up is necessary to better understand the long term effects of ERT in infantile Pompe survivors, especially those with high sustained antibody titers or advanced cardiac disease at treatment outset.
PMCID: PMC2991632  PMID: 20875764
Pompe Disease; Enzyme Replacement Therapy; Cardiac Magnetic Resonance Imaging; Echocardiography; Delayed Enhancement
22.  Skin autofluorescence as a marker of cardiovascular risk in children with chronic kidney disease 
We examined skin autofluorescence (sAF) in chronic kidney disease children (CKD) in relation to renal function and dialysis modality.
Twenty children on hemodialysis (HD), 20 on peritoneal dialysis (PD), 36 treated conservatively, and 26 healthy subjects were enrolled into the study. In all children sAF, pulse-wave velocity indexed to height (PWV/ht), left ventricular mass index (LVMI), blood pressure (BP), serum lipid profile, phosphate (P), calcium (Ca), and homocysteine were measured.
sAF was significantly elevated in CKD groups vs. controls and was significantly associated with PWV/ht, LVMI, BP, P, Ca × P product and homocysteine. sAF in HD and PD groups was positively correlated with dialysis vintage, and in the predialysis group negatively correlated with glomerular filtration rate (eGFR). Multiple regression analysis showed significant association of sAF with LVMI and P in the CKD patient group, and with dialysis treatment duration and BP in dialyzed children.
In CKD children, tissue accumulation of advanced glycation end-products (AGEs) was observed. This was aggravated as eGFR declined and was related to early cardiovascular changes and some biochemical cardiovascular disease (CVD) risk markers. sAF as a non-invasive method may be a useful tool for identification of a clinical risk factors of cardiovascular disease in CKD children.
PMCID: PMC3505501  PMID: 22976887
Cardiovascular risk factors; Children; Dialysis; Nephrology
23.  Addition of Aliskiren to Angiotensin Receptor Blocker Improves Ambulatory Blood Pressure Profile and Cardiorenal Function Better than Addition of Benazepril in Chronic Kidney Disease 
An altered ambulatory blood pressure (BP) and heart rate (HR) profile is related to chronic kidney disease (CKD) and cardiorenal syndrome. In this study, we examined the effects of aliskiren, when added to angiotensin II type 1 receptor blockers, on ambulatory BP and cardiorenal function in CKD. Thirty-six hypertensive CKD patients were randomly assigned to the aliskiren add-on group (n = 18) or the benazepril add-on group (n = 18). Ambulatory BP and cardiorenal function parameters were measured at baseline and 24 weeks after treatment. Compared with the benazepril group, nighttime systolic BP variability in the aliskiren group was lower after treatment. Albuminuria was decreased in the aliskiren group, but not in the benazepril group. In addition, left ventricular mass index (LVMI) was significantly lower in the aliskiren group than in the benazepril group after treatment. In the aliskiren group, multivariate linear regression analysis showed an association between changes in albuminuria and changes in nighttime systolic BP. Furthermore, there were associations between changes in LVMI and changes in daytime HR variability, as well as between changes in LVMI and changes in plasma aldosterone concentration. These results suggest that aliskiren add-on therapy may be beneficial for suppression of renal deterioration and pathological cardiac remodeling through an improvement that is effected in ambulatory BP and HR profiles.
PMCID: PMC3759864  PMID: 23887656
albuminuria; ambulatory blood pressure; direct renin inhibitor; left ventricular hypertrophy; hypertension (kidney)
24.  The Association Between Left Ventricular Hypertrophy and Biomarkers in Patients on Continuous Ambulatory Peritoneal Dialysis 
Korean Circulation Journal  2009;39(11):488-493.
Background and Objectives
Left ventricular hypertrophy (LVH) is a major cardiovascular complication and an important predictor of mortality in patients with end stage renal disease. Some studies have shown that the serum aldosterone levels are correlated with LVH in non-diabetic patients undergoing hemodialysis. The objective of this study was to elucidate the relationships between serum biomarkers, including aldosterone, and echocardiographic findings, such as LVH, in patients on peritoneal dialysis.
Subjects and Methods
Thirty patients on continuous ambulatory peritoneal dialysis (CAPD) for >12 months at Soonchunhyang University Cheonan Hospital were included. Transthoracic echocardiography was performed and the left ventricular mass index (LVMI) was calculated using the Devereux formula. Serum biomarkers {N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin T, C-reactive protein, renin, and aldosterone} were measured.
Sixteen of 30 patients had LVH on the basis of the LVMI. The mean serum aldosterone level was 62.53±60.73 pg/mL (range, 5.03-250.68 pg/mL). LVH, on the basis of the LVMI, was not correlated with the serum aldosterone level. The serum aldosterone levels were not associated with echocardiographic findings, even with co-existing diabetes mellitus. The LVMI had a negative correlation with the hemoglobin (r=-0.405, p=0.029) and hematocrit (r=-0.374, p=0.042), and a positive correlation with NT-proBNP (r=0.560, p=0.002). The other biomarkers (renin, aldosterone, troponin T, and C-reactive protein) were not correlated with the LVMI. The LVMI was correlated with the left atrium volume index (r=0.675, p<0.001).
NT-proBNP is a good marker to predict LVH in patients undergoing CAPD. The serum aldosterone level is not correlated with LVMI, even with co-existing diabetes mellitus.
PMCID: PMC2790132  PMID: 19997545
Aldosterone; Left ventricular hypertrophy; Peritoneal dialysis; Type-B natriuretic peptide
25.  Comparison of Blood Pressure Control and Left Ventricular Hypertrophy in Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) and Automated Peritoneal Dialysis (APD) 
This study aimed to investigate the influence of different peritoneal dialysis regimens on blood pressure control, the diurnal pattern of blood pressure and left ventricular hypertrophy in patients on peritoneal dialysis. Forty-four patients undergoing peritoneal dialysis were enrolled into the study. Patients were treated with different regimens of peritoneal dialysis: 26 patients on continuous ambulatory peritoneal dialysis (CAPD) and 18 patients on automated peritoneal dialysis (APD). All patients performed 24-hour ambulatory blood pressure monitoring (ABPM) and echocardiography. Echocardiography was performed for measurement of cardiac parameters and calculation of left ventricular mass index (LVMI). There were no significant differences in average of systolic and diastolic blood pressure during 24-hour, daytime, and nighttime between CAPD and APD groups. There were no significant differences in diurnal variation of blood pressure, systolic and diastolic blood pressure load, and LVMI between CAPD and APD groups. LVMI was associated with 24 hour systolic blood pressure load (r = 0.311, P < 0.05) and daytime systolic blood pressure load (r = 0.360, P < 0.05). In conclusion, this study found that there is no difference in blood pressure control, diurnal variation of blood pressure and left ventricular hypertrophy between CAPD and APD patients. The different peritoneal dialysis regimens might not influence blood pressure control and diurnal variation of blood pressure in patients on peritoneal dialysis.
PMCID: PMC3186892  PMID: 21998602
blood pressure monitoring, ambulatory; continuous ambulatory peritoneal dialysis (CAPD); automated peritoneal dialysis (APD); left ventricular mass index

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