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1.  Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized controlled trial 
In this issue of the journal, Agarwal et al. report the very first study to make a head-to-head comparison of a beta-blocker with an ACEi, the Hypertension in Haemodialysis Patients Treated with Atenolol or Lisinopril (HDPAL) trial, which was recently presented at the 2013 ASN Congress in Atlanta.
Background
The purpose of this study was to determine among maintenance hemodialysis patients with echocardiographic left ventricular hypertrophy and hypertension whether in comparison with a β-blocker-based antihypertensive therapy, an angiotensin converting enzyme-inhibitor-based antihypertensive therapy causes a greater regression of left ventricular hypertrophy.
Methods
Subjects were randomly assigned to either open-label lisinopril (n = 100) or atenolol (n = 100) each administered three times per week after dialysis. Monthly monitored home blood pressure (BP) was controlled to <140/90 mmHg with medications, dry weight adjustment and sodium restriction. The primary outcome was the change in left ventricular mass index (LVMI) from baseline to 12 months.
Results
At baseline, 44-h ambulatory BP was similar in the atenolol (151.5/87.1 mmHg) and lisinopril groups, and improved similarly over time in both groups. However, monthly measured home BP was consistently higher in the lisinopril group despite the need for both a greater number of antihypertensive agents and a greater reduction in dry weight. An independent data safety monitoring board recommended termination because of cardiovascular safety. Serious cardiovascular events in the atenolol group occurred in 16 subjects, who had 20 events, and in the lisinopril group in 28 subjects, who had 43 events {incidence rate ratio (IRR) 2.36 [95% confidence interval (95% CI) 1.36–4.23, P = 0.001]}. Combined serious adverse events of myocardial infarction, stroke and hospitalization for heart failure or cardiovascular death in the atenolol group occurred in 10 subjects, who had 11 events and in the lisinopril group in 17 subjects, who had 23 events (IRR 2.29, P = 0.021). Hospitalizations for heart failure were worse in the lisinopril group (IRR 3.13, P = 0.021). All-cause hospitalizations were higher in the lisinopril group [IRR 1.61 (95% CI 1.18–2.19, P = 0.002)]. LVMI improved with time; no difference between drugs was noted.
Conclusions
Among maintenance dialysis patients with hypertension and left ventricular hypertrophy, atenolol-based antihypertensive therapy may be superior to lisinopril-based therapy in preventing cardiovascular morbidity and all-cause hospitalizations. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number: NCT00582114)
doi:10.1093/ndt/gft515
PMCID: PMC3938300  PMID: 24398888
hemodialysis; hypertension; randomized trial
2.  Clinical Correlates and Prognostic Significance of Change in Standardized Left Ventricular Mass in a Community‐Based Cohort of African Americans 
Background
Though left ventricular mass (LVM) predicts cardiovascular events (CVD) and mortality in African Americans, limited data exists on factors contributing to change in LVM and its prognostic significance. We hypothesized that baseline blood pressure (BP) and body mass index (BMI) and change in these variables over time are associated with longitudinal increases in LVM and that such increase is associated with greater incidence of CVD.
Methods and Results
We investigated the clinical correlates of change in standardized logarithmically transformed‐LVM indexed to height2.7 (log‐LVMI) and its association with incident CVD in 606 African Americans (mean age 58±6 years, 66% women) who attended serial examinations 8 years apart. Log‐LVMI and clinical covariates were standardized within sex to obtain z scores for both visits. Standardized log‐LVMI was modeled using linear regression (correlates of change in standardized log‐LVMI) and Cox proportional hazards regression (incidence of CVD [defined as coronary heart disease, stroke, heart failure and intermittent claudication]). Baseline clinical correlates (standardized log‐LVM, BMI, systolic BP) and change in systolic BP over time were significantly associated with 8‐year change in standardized log‐LVMI. In prospective analysis, change in standardized LVM was significantly (P=0.0011) associated with incident CVD (hazards ratio per unit standard deviation change log‐LVMI 1.51, 95% CI 1.18 to 1.93).
Conclusions
In our community‐based sample of African Americans, baseline BMI and BP, and change in BP on follow‐up were key determinants of increase in standardized log‐LVMI, which in turn carried an adverse prognosis, underscoring the need for greater control of BP and weight in this group.
doi:10.1161/JAHA.114.001224
PMCID: PMC4345860  PMID: 25655570
African Americans; blood pressure; cardiovascular disease; cardiovascular events; left ventricular mass risk factors
3.  Cross-sectional association of volume, blood pressures, and aortic stiffness with left ventricular mass in incident hemodialysis patients: the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) study 
BMC Nephrology  2015;16:131.
Background
Higher left ventricular mass (LV) strongly predicts cardiovascular mortality in hemodialysis patients. Although several parameters of preload and afterload have been associated with higher LV mass, whether these parameters independently predict LV mass, remains unclear.
Methods
This study examined a cohort of 391 adults with incident hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study. The main exposures were systolic and diastolic blood pressure (BP), pulse pressure, arterial stiffness by pulse wave velocity (PWV), volume status estimated by pulmonary pressures using echocardiogram and intradialytic weight gain. The primary outcome was baseline left ventricular mass index (LVMI).
Results
Each systolic, diastolic blood, and pulse pressure measurement was significantly associated with LVMI by linear regression regardless of dialysis unit BP or non-dialysis day BP measurements. Adjusting for cardiovascular confounders, every 10 mmHg increase in systolic or diastolic BP was significantly associated with higher LVMI (SBP β = 7.26, 95 % CI: 4.30, 10.23; DBP β = 10.05, 95 % CI: 5.06, 15.04), and increased pulse pressure was also associated with higher LVMI (β = 0.71, 95 % CI: 0.29, 1.13). Intradialytic weight gain was also associated with higher LVMI but attenuated effects after adjustment (β = 3.25, 95 % CI: 0.67, 5.83). PWV and pulmonary pressures were not associated with LVMI after multivariable adjustment (β = 0.19, 95 % CI: −1.14, 1.79; and β = 0.10, 95 % CI: −0.51, 0.70, respectively). Simultaneously adjusting for all main exposures demonstrated that higher BP was independently associated with higher LVMI (SBP β = 5.64, 95 % CI: 2.78, 8.49; DBP β = 7.29, 95 % CI: 2.26, 12.31, for every 10 mmHg increase in BP).
Conclusions
Among a younger and incident hemodialysis population, higher systolic, diastolic, or pulse pressure, regardless of timing with dialysis, is most associated with higher LV mass. Future studies should consider the use of various BP measures in examining the impact of BP on LVM and cardiovascular disease. Findings from such studies could suggest that high BP should be more aggressively treated to promote LVH regression in incident hemodialysis patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0131-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0131-4
PMCID: PMC4528691  PMID: 26249016
4.  Assessment of left ventricular mass index could predict metabolic syndrome in obese children 
Background
Childhood obesity is a major risk factor for cardiovascular diseases in children and adults.
Objectives
The purpose of this study was to evaluate the serum leptin level and the cardiac changes in normotensive obese children and to study the relationship between left ventricular mass index (LVMI) and serum leptin with the parameters of metabolic syndrome (MS) in obese children.
Methods
This study was conducted in al Jeddani Hospital and Ibn Sina College Hospital in Saudi Arabia in the period from July 2012 to December 2013, and included 82 obese children. Their mean age was 10.2 ± 2.8 years; they were divided into 25 obese children with MS and 57 obese children without MS, and 40 healthy age- and sex-matched children were also included in the study as a control group. All children were subjected to clinical assessment including standing height, body weight, body mass index (BMI), waist circumference (WC), and blood pressure measurements. All children received an echocardiographic examination (2-dimensional, M-mode, Doppler, and tissue Doppler echocardiograpy) and laboratory assessment of serum leptin level, fasting glucose, fasting insulin, the homeostatic model assessment for insulin resistance (HOMA) index, total cholesterol, triglycerides, and high- and low-density lipoprotein profile.
Results
BMI, BMI standard deviation score, WC, fasting glucose, fasting insulin, HOMA index and the serum leptin level were significantly higher in obese children compared to control group (p < 0.05). The LVMI were increased in the obese compared to the control group (p < 0.001) while left ventricle systolic and diastolic functions did not differ in obese versus control group (p > 0.05). There was a significant positive correlation between both LVMI and serum leptin level in comparison to BMI, WC, fasting glucose, fasting insulin, HOMA, triglycerides, and low-density lipoprotein in all obese children, especially the MS group. However, there was a significant negative correlation between both LVMI and serum leptin level in comparison to high-density lipoprotein.
Conclusion
Assessment of LVMI as routine echocardiographic examinations and serum leptin level might be a feasible and reliable method for the evaluation of obesity and its related cardiovascular risks during childhood that can predict metabolic syndrome and insulin resistance.
doi:10.1016/j.jsha.2015.06.002
PMCID: PMC4917708  PMID: 27358533
Left ventricular mass index; Metabolic syndrome; Obese children; Serum leptin
5.  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.
doi:10.3390/ijms14011069
PMCID: PMC3565307  PMID: 23296279
nitrate; ADMA; hypertension; left ventricular hypertrophy; renal dialysis
6.  Effects of Azelnidipine plus OlmesaRTAn versus amlodipine plus olmesartan on central blood pressure and left ventricular mass index: the AORTA study 
Purpose:
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.
Results:
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).
Conclusions:
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.
doi:10.2147/VHRM.S21991
PMCID: PMC3141910  PMID: 21796252
central blood pressure; left ventricular mass index; augmentation index; brachial-ankle pulse wave velocity; olmesartan/azelnidipine
7.  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.
doi:10.1038/jhh.2010.25
PMCID: PMC3037860  PMID: 20237502
left ventricular mass; endothelial function; brachial flow-mediated dilation; population
8.  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.
doi:10.1161/HYPERTENSIONAHA.111.180091
PMCID: PMC3241970  PMID: 22042814
Body mass index; epidemiology; hemodialysis; ambulatory blood pressure; left ventricular hypertrophy; survival
9.  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 
Background
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1186/1476-7120-8-29
PMCID: PMC2923627  PMID: 20659321
10.  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.
doi:10.1016/S0011-393X(03)00007-9
PMCID: PMC4053024  PMID: 24944353
essential hypertension; combination therapy; trandolapril; verapamil
11.  Shorter delivered dialysis times associate with a higher and more difficult to treat blood pressure 
Nephrology Dialysis Transplantation  2013;28(6):1562-1568.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1093/ndt/gfs597
PMCID: PMC3685306  PMID: 23348881
hemodialysis; hypertension
12.  The Relationship between Adiponectin and Left Ventricular Mass Index Varies with the Risk of Left Ventricular Hypertrophy 
PLoS ONE  2013;8(7):e70246.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1371/journal.pone.0070246
PMCID: PMC3722139  PMID: 23894624
13.  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 
Purpose
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1186/1476-7120-11-18
PMCID: PMC3679950  PMID: 23731705
Transcatheter aAortic valve implantation; Doppler echocardiography; Relative wall thickness; Left ventricular mass
14.  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.
doi:10.4103/0971-4065.59337
PMCID: PMC2875705  PMID: 20535251
Hemodialysis; hypertension; hyperparathyroidism; left ventricular hypertrophy
15.  Effect of Frequent or Extended Hemodialysis on Cardiovascular Parameters: A Meta-analysis 
Background
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
Meta-analysis.
Setting & Population
MEDLINE literature search (inception-April 2011), Cochrane Central Register of Controlled Trials and ClinicalTrials.gov 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.
Intervention
Frequent (2–8 hours,> thrice weekly) or extended (>4 hours, thrice weekly) HD as compared with conventional (≤ 4 hours, thrice weekly) HD.
Outcomes
Absolute changes in cardiac morphology and function, including LV mass index (LVMI) (primary), and blood pressure parameters (secondary).
Results
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.
Limitations
Paucity of randomized controlled trials.
Conclusions
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.
doi:10.1053/j.ajkd.2011.12.020
PMCID: PMC3395217  PMID: 22370022
frequent HD; extended HD; conventional HD; LVMI; meta-analysis
16.  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.
Results
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.
Conclusion
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.
doi:10.4070/kcj.2011.41.10.583
PMCID: PMC3221900  PMID: 22125557
Hypertension; Valsartan
17.  Left ventricular mass index in children with white coat hypertension 
The Journal of pediatrics  2008;153(1):50-54.
Objective
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.
Results
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).
Conclusions
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.
doi:10.1016/j.jpeds.2008.01.025
PMCID: PMC2516747  PMID: 18571535
18.  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.
doi:10.3390/ijms140816866
PMCID: PMC3759940  PMID: 23959116
ambulatory blood pressure; calcium channel blockers; cardiac hypertrophy; chronic kidney disease; heart rate variability; hypertension (kidney)
19.  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.
doi:10.1093/ndt/gfq210
PMCID: PMC2948838  PMID: 20400448
ambulatory BP; dry weight; haemodialysis; hypertension; sodium
20.  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.
doi:10.4274/jcrpe.v3i3.26
PMCID: PMC3184514  PMID: 21911326
obesity; metabolic syndrome; cardiovascular disease; left ventricular mass index; children
21.  Forty-four-hour interdialytic ambulatory blood pressure monitoring and cardiovascular risk in pediatric hemodialysis patients 
Clinical Kidney Journal  2013;7(1):33-39.
Background
Children undergoing chronic hemodialysis are at risk of cardiovascular disease and often develop left ventricular hypertrophy (LVH). Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is known to better predict cardiovascular morbidity than casual blood pressure (BP) measurement. Given the BP variability attributed to interdialytic fluid overload, 44-h ABPM should better delineate cardiovascular morbidity in pediatric hemodialysis patients.
Methods
In this cross-sectional study, 17 children (16.7 ± 2.9 years) on chronic hemodialysis underwent 44-h interdialytic ABPM and routine echocardiogram. Left ventricular mass index (LVMI) was calculated by height-based equation; LVH was defined as an LVMI in the ≥95th percentile for height-age and gender. Hypertension was defined by the recommendations of the Fourth Report of the National High Blood Pressure Education Program for casual measurements, and by those of the American Heart Association for ABPM.
Results
Twenty-four percentage of patients were hypertensive by casual post-dialytic systolic BP, whereas 59% were hypertensive by ABPM. Eighty-eight percentage of patients had abnormal cardiac geometry: 53% had LVH. Thirty-five percentage (6 of 17) had masked hypertension, including four with abnormal cardiac geometry, of which, three had LVH. LVMI correlated with ABPM, but not with casual measurements. Strongest correlations with an increased LVMI were with 44-h diastolic BP: at night (r = 0.53, P = 0.03) and total load (r = 0.57, P = 0.02). LVH was similarly associated with 44-h nighttime BP: systolic (P = 0.02), diastolic (P = 0.01) and mean arterial (P = 0.01).
Conclusions
Casual BP measurement underestimates hypertension in pediatric hemodialysis patients and does not correlate well with indicators of cardiovascular morbidity. In contrast, 44-h interdialytic ABPM better characterizes hypertension, with nighttime parameters most strongly predicting increased LVMI and LVH.
doi:10.1093/ckj/sft149
PMCID: PMC4389162  PMID: 25859347
blood pressure; children; hemodialysis; hypertension; left ventricular hypertrophy
22.  Changes in Echocardiographic Parameters According to the Rate of Residual Renal Function Decline in Incident Peritoneal Dialysis Patients 
Medicine  2015;94(7):e427.
Supplemental Digital Content is available in the text
Abstract
Residual renal function (RRF) is associated with left ventricular (LV) hypertrophy as well as all-cause and cardiovascular (CV) mortality in patients with end-stage renal disease. However, no studies have yet examined the serial changes in echocardiographic findings according to the rate of RRF decline in incident dialysis patients.
A total of 81 patients who started peritoneal dialysis (PD) between 2005 and 2012 at Yonsei University Health System, Seoul, South Korea, and who underwent baseline and follow-up echocardiography within the first year of PD were recruited. Patients were dichotomized into “faster” and “slower” RRF decline groups according to the median values of RRF decline slope (−1.60 mL/min/y/1.73 m2).
Baseline RRF and echocardiographic parameters were comparable between the 2 groups. During the first year of PD, there were no significant changes in LV end-diastolic volume index (LVEDVI), left atrial volume index (LAVI), or LV mass index (LVMI) in the “faster” RRT decline group, while these indices decreased in the “slower” RRT decline group. The rate of RRF decline was a significant determinant of 1-year changes in LVEDVI, LAVI, and LVMI. The linear mixed model further confirmed that there were significant differences in the changes in LVEDVI, LAVI, and LVMI between the 2 groups (P = 0.047, 0.048, and 0.001, respectively). During a mean follow-up duration of 31.9 months, 4 (4.9%) patients died. Compared with the “slower” RRF decline group, CV composite (20.29/100 vs 7.18/100 patient-years [PY], P = 0.098), technique failure (18.80/100 vs 4.19/100 PY, P = 0.006), and PD peritonitis (15.73/100 vs 4.95/100 PY, P = 0.064) developed more frequently in patients with “faster” RRF decline rate. On multivariate Cox regression analysis, patients with “faster” RRF decline rate showed 4.82-, 4.44-, and 7.37-fold higher risks, respectively, for each clinical outcome.
Preservation of RRF is important for conserving cardiac performance, resulting in an improvement in clinical outcomes of incident PD patients.
doi:10.1097/MD.0000000000000427
PMCID: PMC4554171  PMID: 25700308
23.  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.
Aims
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).
Conclusion
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.
doi:10.1093/eurheartj/ehu389
PMCID: PMC4258225  PMID: 25246483
Blood pressure; Left ventricular mass; Left ventricular hypertrophy; Echocardiography
24.  Hyperglycemia and nocturnal systolic blood pressure are associatedwith left ventricular hypertrophy and diastolic dysfunction in hypertensive diabetic patients 
Background
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.
Methods
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).
Results
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.
Conclusion
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.
doi:10.1186/1475-2840-5-19
PMCID: PMC1579206  PMID: 16968545
25.  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.
doi:10.3892/etm.2013.1339
PMCID: PMC3829736  PMID: 24255684
left ventricular hypertrophy; apoptosis; tanshinone IIA; p53; Bcl-2; Bax

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