Prevention Of Left Ventricular Hypertrophy Research Articles

PS-C13-1: PREVALENCE AND ASSOCIATED FACTORS OF LEFT VENTRICULAR HYPERTROPHY IN ASYMPTOMATIC HYPERTENSIVE PATIENTS

Introduction: Left ventricular hypertrophy (LVH) is a major target organ impairment in hypertensive patients, LVH is an independent cardiovascular risk factor. The objective of our work is to detect and analyze the factors associated with electrical left ventricular hypertrophy in asymptomatic hypertensive patients. Method: Prospective study of a cohort of asymptomatic hypertensive patients, aged over 35, seen in consultation. All patients had undergone a 12 lead ECG examination looking for left ventricular hypertrophy defined by Sokolow Lyon index > 3.5 mV and/or RaVL> 1.1 mV and/or Cornell voltage duration product > 244 mV ms Results: 263 patients evaluated during the study period, 151 women or 57% and 112 men or 43%, the average age of the population is 59.78 years ± 10.67 [36 to 87 years]. Left ventricular hypertrophy is observed in 52 patients, i.e. 19.7% of asymptomatic hypertensives. These are 31 women (20.3% of women) and 21 men (18.75% of men). The analysis of the subgroups finds a high prevalence of electrical LVH between 45 and 55 years and between 55 and 65 years with ORs at 7.80 [0.97, 62.37] p = 0.0528 and at 7.76 [0.99, 60.82] p = 0.0511. Regarding the blood pressure profile, LVH is strongly associated with systolic blood pressure levels. The analysis of the subgroups of the seniority of hypertension finds an increase in the OR to 2.95 in the group of 1 to 5 years of seniority with significant p at 0.02. After the multivariate analysis, the two independent risk factors associated with the development of electrical left ventricular hypertrophy are: Systolic Blood Pressure level between 140 and 179 mmHg and Total Cholesterol level greater than 2 g/l. The p is very significant (0.016 and 0.025 respectively) Conclusion: LVH is common in our series, it affects 19.7% of our asymptomatic hypertensive patients. The most affected age group is from 45 to 65 years old whose seniority from the time of diagnosis is less than 5 years. The two factors associated with LVH are systolic blood pressure and total cholesterol level. In the light of these results, the prevention of LVH must associate; Early screening by ECG at the time of diagnosis and during the first 5 years, management of hypertension with a target SBP of less than 140 and a cholesterol level of less than 2 g/l

An Optimized Model of Hypertrophic Preconditioning Confers Cardioprotection in the Mouse

BackgroundConventional models of hypertrophic preconditioning (C-HP) can be established surgically through transverse aortic constriction (TAC) → deconstriction (De-TAC) → reconstriction (Re-TAC) characterized by dynamic afterload while it exerts technical difficulty on operators and poses high mortality during perioperative period in mice. We aimed to introduce an optimized method for obtaining a hypertrophic preconditioning (O-HP) model for further study on cardiac hypertrophy. MethodsNinety mice were divided into four groups: sham, TAC, C-HP, and O-HP. The sham group was exerted on three-time thoracotomies. The TAC group experienced twice thoracotomies and one TAC operation. C-HP and O-HP groups were given TAC, De-TAC, and Re-TAC operation at day 0, day 3, and day 7 in conventional and optimized method, respectively. We optimized the operating procedure in O-HP mice compared with the C-HP group by (1) leaving a ∼3-cm suture fixed in the subcutaneous layer after aortic constriction in TAC surgery (2) using two small forceps to untie the constriction knot instead of cutting it in the De-TAC operation. Ultrasound biomicroscopy was used for hemodynamics and cardiac function detection. Four weeks after the third surgery, all mice were sacrificed and pathology was analyzed among four groups. ResultsFour weeks after Re-TAC, the survival of O-HP mice was 63.3% while that of C-HP was 26.7%. Ultrasound biomicroscopy showed a successful establishment of HP models. C-HP and O-HP mice had improved cardiac structure and function indicated by left ventricular end-systolic diameter, left ventricular end-systolic posterior wall thickness, left ventricular ejection fraction, and left ventricular fractional shortening than the TAC group. Pathological analysis showed O-HP as well as C-HP had less hypertrophy than the TAC mice. ConclusionsOur results provide a rapid, safe, efficient, and reproducible method for optimized establishment of the HP model, which will facilitate studies for early intervention and prevention of left ventricular hypertrophy and heart failure.

Localized Antileptin Therapy Prevents Aortic Root Dilatation and Preserves Left Ventricular Systolic Function in a Murine Model of Marfan Syndrome.

BackgroundMarfan syndrome (MFS) is a genetically transmitted connective tissue disorder characterized by aortic root dilatation, dissection, and rupture. Molecularly, MFS pathological features have been shown to be driven by increased angiotensin II in the aortic wall. Using an angiotensin II–driven aneurysm mouse model, we have recently demonstrated that local inhibition of leptin activity restricts aneurysm formation in the ascending and abdominal aorta. As we observed de novo leptin synthesis in the ascending aortic aneurysm wall of patients with MFS, we hypothesized that local counteracting of leptin activity in MFS may also prevent aortic cardiovascular complications in this context.Methods and Results Fbn1 C1039G/+ mice underwent periaortic application of low‐dose leptin antagonist at the aortic root. Treatment abolished medial degeneration and prevented increase in aortic root diameter (P<0.001). High levels of leptin, transforming growth factor β1, Phosphorylated Small mothers against decapentaplegic 2, and angiotensin‐converting enzyme 1 observed in saline‐treated MFS mice were downregulated in leptin antagonist–treated animals (P<0.01, P<0.05, P<0.001, and P<0.001, respectively). Leptin and angiotensin‐converting enzyme 1 expression levels in left ventricular cardiomyocytes were also decreased (P<0.001) and coincided with prevention of left ventricular hypertrophy and aortic and mitral valve leaflet thickening (P<0.01 and P<0.05, respectively) and systolic function preservation.ConclusionsLocal, periaortic application of leptin antagonist prevented aortic root dilatation and left ventricular valve remodeling, preserving left ventricular systolic function in an MFS mouse model. Our results suggest that local inhibition of leptin may constitute a novel, stand‐alone approach to prevent MFS aortic root aneurysms and potentially other similar angiotensin II–driven aortic pathological features.

Dry Extract of Passiflora incarnata L. leaves as a Cardiac and Hepatic Oxidative Stress Protector in LDLr-/- Mice Fed High-Fat Diet

ABSTRACT The control of dyslipidemia by using herbal products is an important subject for studies. In this study, we evaluated the effects of dry Passiflora incarnata L. extract over dyslipidemia, left ventricular hypertrophy, and hepatic oxidative stress of LDL receptor knockout mice (LDLr-/-). Forty 4-month old male LDLr-/- mice were distributed into four groups: Group standard diet; Group standard diet and 200 mg/kg of body weight of Passiflora incarnata L. leaf dry extract; Group high-fat diet; Group high-fat diet and 200 mg/kg of body weight of Passiflora incarnata L. leaf dry extract. After 30 days, Passiflora incarnata L. dry extract reduced the effects of the high-fat diet, with a decrease of total cholesterol, triglycerides, and increase of high-density lipoprotein (HDL), as well as a reduction of C-reactive protein, alkaline phosphatase and insulin. There was no effect on glucose, Homa index and enzymes aspartate aminotransferase and alanine aminotransferase. However, the prevention of left ventricular hypertrophy occurred, as well as lipid peroxidation and the production of carbonyl proteins, which are both oxidative stress markers. In conclusion, Passiflora incarnata L. dry extract acts in the prevention of dyslipidemia, consequently, hindering the occurrence of hepatic oxidative stress and the development of left ventricular hypertrophy by the increase of serum HDL, in mice that had the effects of a high-fat diet.

Intensive Home Hemodialysis Results in Regression of Left Ventricular Hypertrophy and Better Clinical Outcomes

Background: Left ventricular hypertrophy (LVH) is an independent risk factor for mortality and cardiovascular events in patients with end-stage renal disease. Studies have shown that frequent hemodialysis leads to LVH regression, but the impact of left ventricular mass (LVM) regression on clinical outcomes remains unknown. Methods: This observational cohort study assessed the impact of LVH regression on the composite outcome of time to all-cause mortality, technique failure or cardiovascular hospitalization in patients on home hemodialysis. LVH regression was defined as either a reduction of more than 10% in LVM in patients with LVH at baseline or prevention of LVH in those without LVH at baseline. Risk factors associated with progression of LVM were also examined. Results: We studied 144 intensive hemodialysis patients between 1999 and 2012 with a mean follow-up of 4.7 years. Eighty-seven patients (60.4%) had LVH regression or prevention and 57 patients (39.6%) had LVH progression. In a multivariate analysis, smoking (OR 2.78, 95% CI 1.06-7.36) and presence of LVH at baseline (OR 2.21, 95% CI 1.06-4.59) were significant predictors for LVM progression. Sixteen patients (18.4%) in the regressor group and 19 patients (33.3%) in the progressor group developed the composite end point. When adjusted for age and diabetes, regression was significantly associated with a decreased risk (hazards ratio (HR) 0.42, 95% CI 0.21-0.84) for the composite end point. Regression was also significantly associated with a decreased risk of death in the adjusted analysis (HR 0.20, 95% CI 0.06-0.67). Conclusions: Regression of LVH with intensive hemodialysis is associated with favorable clinical outcomes.

Influence of Physical Activity on Hypertension and Cardiac Structure and Function.

The global burden of hypertension is rising and accounts for substantial morbidity and mortality. Lifestyle factors such as diet and physical inactivity contribute to this burden, further highlighting the need for prevention efforts to curb this public health epidemic. Regular physical activity is associated with lower blood pressure, reduced cardiovascular risk, and cardiac remodeling. While exercise and hypertension can both be associated with the development of left ventricular hypertrophy (LVH), the cardiac remodeling from hypertension is pathologic with an associated increase in myocyte hypertrophy, fibrosis, and risk of heart failure and mortality, whereas LVH in athletes is generally non-pathologic and lacks the fibrosis seen in hypertension. In hypertensive patients, physical activity has been associated with paradoxical regression or prevention of LVH, suggesting a mechanism by which exercise can benefit hypertensive patients. Further studies are needed to better understand the mechanisms underlying the benefits of physical activity in the hypertensive heart.

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.

The Impact of Left Ventricular Hypertrophy as a Risk of Heart Failure with Preserved Ejection Fraction

Many epidemiological studies have revealed a close relation between left ventricular (LV) hypertrophy and prognosis of patients with cardiovascular diseases, including heart failure with preserved ejection fraction (HFpEF). Hypertension is a leading cause for HFpEF, and depressor therapy is mandatory and effective in the prevention of LV hypertrophy. However, in some of hypertensive patients, LV hypertrophy progresses even after the reduction of blood pressure or in the absence of hypertension. Our and other experimental studies have suggested that LV hypertrophy is not a homogeneous phenomenon, and that there are at least two types in hypertensive heart disease; adaptive and excessive hypertrophy.

Cardoguard, an Ayurvedic antihypertensive formulation, prevents cardiac remodeling in spontaneously hypertensive rats by inhibition of ERK and PKCε signaling pathways

Ayurveda is an Indian system of medicine. Despite clinical efficacy, lack of scientific validation has limited the effective use of Ayurvedic drugs. Cardoguard is an Ayurvedic antihypertensive drug formulated by Nagarjuna Herbal Concentrates Ltd., Kerala, India. Left ventricular hypertrophy (LVH) is a modifiable risk factor, and regression of LVH reduces the propensity for adverse cardiovascular events. This study was taken up with the objective of evaluating the efficacy of Cardoguard in the prevention of cardiac remodeling. Cardoguard was administered orally to 2-month-old spontaneously hypertensive rats for 4 months at a dose of 5 mg·day(-1). The dose corresponds to the therapeutic dose calculated on the basis of body surface area. Lower hypertrophy index, decrease in cardiomyocyte area, and reduction of interstitial fibrosis in treated spontaneously hypertensive rats indicate amelioration of cardiac hypertrophy by Cardoguard. Cardiac output increased in response to treatment. Immunostaining for the phosphorylated components of major signaling pathways associated with hypertrophy suggests that prevention of LVH by Cardoguard is possibly mediated through inhibition of extracellular signal-regulated kinases and protein kinase C-ε signaling pathways. Reduced expression of 3-nitrotyrosine in response to the treatment suggests that prevention of cardiac remodeling by Cardoguard is mediated by reduction of oxidative stress.

Reactivation of Peroxisome Proliferator-activated Receptor Alpha in Spontaneously Hypertensive Rat: Age-associated Paradoxical Effect on the Heart

Prevention of left ventricular hypertrophy remains a challenge in the prevention of hypertension-induced adverse cardiac remodeling. Cardiac hypertrophy is associated with a shift in energy metabolism from predominantly fatty acid to glucose with a corresponding reduction in the expression of fatty acid oxidation enzyme genes. Although initially adaptive, the metabolic switch seems to be detrimental in the long run. This study was taken up with the objective of examining whether the stimulation of fatty acid oxidation by the activation of peroxisome proliferator-activated receptor alpha (PPARα), a key regulator of fatty acid metabolism, can prevent cardiac hypertrophy. Fenofibrate was used as the PPARα agonist. Spontaneously hypertensive rats (SHRs) in the initial stages of hypertrophy (2 months) and those with established hypertrophy (6 months) were treated with fenofibrate (100 mg·kg·d for 60 days). Cluster of differentiation 36 (CD36)-responsible for myocardial fatty acid uptake, carnitine palmitoyl transferase 1β-a mitochondrial transporter protein and medium chain acyl-Co-A dehydrogenase-a key enzyme in beta oxidation of fatty acids were selected as indicators of fatty acid metabolism. Hypertrophy was apparent at 2 months and metabolic shift at 4 months of age in SHRs. The treatment prevented cardiac remodeling in young animals but aggravated hypertrophy in older animals. Hypertrophy showed a positive association with malondialdehyde levels and cardiac NF-κB gene expression, signifying the role of oxidative stress in the mediation of hypertrophy. Expression of carnitine palmitoyl transferase 1β and medium chain acyl-Co-A dehydrogenase was upregulated on treatment. However, CD36 showed an age-dependent variation on treatment, with no change in expression in young rats and downregulation in older animals. It is inferred that the stimulation of PPARα before the initiation of metabolic remodeling may prevent cardiac hypertrophy, but reactivation after the metabolic adaptation aggravates hypertrophy. Whether the downregulation of CD36 is mediated by decreased substrate availability remains to be explored. Age-dependent paradoxical effect on the heart in response to fenofibrate, used as a lipid-lowering drug, can have therapeutic implications.

Therapeutic Effects of Vitamin D Analogs on Cardiac Hypertrophy in Spontaneously Hypertensive Rats

Vitamin D inhibits renin expression and blocks the compensatory induction of renin associated with the use of renin-angiotensin system inhibitors. Here we test the therapeutic effects of two commonly used vitamin D analogs and their combination with losartan on the development of left ventricular hypertrophy. One-month-old male spontaneously hypertensive rats were treated with vehicle, losartan, paricalcitol, doxercalciferol, a combination of losartan and paricalcitol, or a combination of losartan and doxercalciferol for 2 months. Blood pressure was markedly reduced by losartan, but not by paricalcitol or doxercalciferol alone. Echocardiograpy demonstrated a 65 to 80% reduction in left ventricular wall thickness with losartan, paricalcitol, or doxercalciferol monotherapy and almost complete prevention of left ventricular hypertrophy with the combination therapies. Attenuation of cardiac and cardiomyocyte hypertrophy, and suppression of atrial and brain natriuretic peptides, were most marked in the combination therapy groups. These changes were well correlated with left ventricular gene and microRNA expression profiles in the different treatment groups. Renal and cardiac renin expression was markedly increased in losartan-treated animals, but nearly normalized with combination therapy. The same vitamin D analogs suppressed plasma renin activity in patients receiving chronic hemodialysis. These data demonstrate that vitamin D analogs have potent antihypertrophic activity in part via suppression of renin in the kidney and heart, and combination of these analogs with losartan achieves much better therapeutic effects because of the blockade of the compensatory renin increase.

A Lower Blood Pressure Goal in Patients Without Diabetes Lessens the Occurrence of Left Ventricular Hypertrophy

A LOWER BLOOD PRESSURE GOAL IN PATIENTS WITHOUT DIABETES LESSENS THE OCCURRENCE OF LEFT VENTRICULAR HYPERTROPHY The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends a blood pressure (BP) goal of <140 ⁄90 mm Hg in most patients with hypertension and a goal of <130 ⁄80 mm Hg in patients with diabetes or chronic kidney disease. A recent scientific statement from the American Heart Association suggested adding patients with known coronary artery disease, carotid disease, peripheral artery disease, an abdominal aortic aneurysm, left ventricular dysfunction, or a calculated 10-year Framingham risk score of at least 10% to the group of patients with a BP goal of <130 ⁄80 mm Hg. These recommendations were made despite a lack of level I clinical trial evidence for benefit of more intensive treatment of BP in those patient populations. These recommendations are largely aimed at reducing the incidence of hard cardiovascular events such as myocardial infarction (MI), stroke, or heart failure. In patients with hypertension, left ventricular hypertrophy (LVH) is a major independent risk factor for stroke, MI, sudden cardiac death, and cardiovascular mortality. Yet, neither JNC 7 nor the American Heart Association (AHA) Scientific Statement specify a more aggressive BP goal in patients with LVH, and prevention of LVH is not emphasized in current guidelines. Whether more aggressive BP lowering would effectively reduce the incidence of LVH was recently tested in the Studio Italiano Sugli Effetti Cardiovascolari del Controllo della Pressione Arteriosa Sistolica (Cardio-Sis) trial. In this open-label, industry-supported trial conducted between February 2005 and February 2007, Italian researchers enrolled 1111 Italian hypertensive nondiabetic patients (93% of those screened). Inclusion criteria included age 55 years or older, a baseline systolic BP of 150 mm Hg, use of antihypertensive therapy for at least 12 weeks, and at least 1 additional risk factor (cigarette smoking, dyslipidemia, family history of premature cardiovascular disease, previous transient ischemic attack or stroke, or established coronary or peripheral artery disease). Patients were excluded if they had a history of diabetes, renal dysfunction, valvular heart disease, liver disease, atrial fibrillation, substance abuse, or a limited life expectancy. Eligible participants entered a run-in phase to make sure that at two visits 7 to 14 days apart their systolic BP on their present antihypertensive regimen was 150 mm Hg. They were then randomized in a 1:1 ratio to receive antihypertensive drug treatment to achieve either usual systolic BP control (<140 mm Hg) (n=553) or tight systolic BP control (130 mm Hg) (n=558). They were followed up every 4 months for 2 years. At baseline and at 1 and 2 years, patients had a 12-lead electrocardiogram (ECG) and laboratory blood tests performed. Treatment was open-label, with all classes of antihypertensive drugs available. Intensification or down-titration of treatment was permitted in order to achieve the specified BP goals. Drug classes were evenly distributed at baseline, except in the usualcontrol group where more patients were taking a diuretic and fewer were taking an angiotensin receptor blocker (ARB). The primary study outFrom the Division of General Internal Medicine ⁄ Division of Cardiology, University of Nevada School of Medicine; the Risk Reduction Center, Saint Mary’s Regional Medical Center, Reno, NV; the Primary Care Service Line, Ralph H. Johnson VA Medical Center, and the Division of General Internal, Medicine ⁄Geriatrics, Medical University of South Carolina, Charleston, SC Address for correspondence: Michael J. Bloch, MD, Risk Reduction Center, Saint Mary’s Regional Medical Center, 645 North Arlington Street, Suite 460, Reno, NV 89503 E-mail: mbloch@aol.com

High-Density Lipoprotein Cholesterol and Left Ventricular Mass Index in Peritoneal Dialysis

The prevalence of left ventricular hypertrophy (LVH) reaches 75% in patients with end-stage renal disease. In patients on peritoneal dialysis (PD), some factors, such as hypertension, volume overload, serum albumin, and residual renal function, have been reported to be related to LVH. Dyslipidemia often occurs in PD but it remains unclear whether dyslipidemia is related to LVH. We investigated the relationship between clinical parameters, including lipid profile, and left ventricular mass index (LVMI). In this cross-sectional study, 34 patients undergoing PD for more than 1 year without combined therapy with hemodialysis were included. We recorded the patients' clinical data and related those parameters with LVMI as evaluated by echocardiography. The patients included 23 males and 11 females (age 62.2 +/- 12.1 years, duration on PD 31.6 +/- 15.6 months). Mean LVMI was 142 +/- 37 g/m2. In univariate analysis, urine volume (r = -0.493, p = 0.003), total cholesterol (r = -0.418, p = 0.01), high-density lipoprotein cholesterol (HDL-C; r = -0.374, p = 0.02), and human atrial natriuretic peptide (hANP; r = 0.600, p < 0.001) significantly correlated with LVMI. Stepwise multiple regression analysis showed that hANP (beta = 0.524, p = 0.001) and HDL-C (beta = -0.422, p = 0.007) were independently associated with LVMI (r2 = 0.32). Strict volume control and salt restriction is essential for prevention of LVH. The role of HDL-C in the development of LVH in PD patients remains to be determined.

Green Tea Attenuates Angiotensin II-Induced Cardiac Hypertrophy in Rats by Modulating Reactive Oxygen Species Production and the Src/Epidermal Growth Factor Receptor/Akt Signaling Pathway1,

We previously documented a clear-cut antihypertensive effect of green teat extract (GTE), which was associated with correction of endothelial dysfunction and prevention of left ventricular hypertrophy in an angiotensin II (Ang II)-dependent model of hypertension, but the molecular mechanisms remain to be defined. As several effects of Ang II involve production of reactive oxygen species (ROS) and activation of 2nd messengers, such as mitogen-activated protein kinase (MAPK) and Akt, we investigated the effect of GTE on these signal transduction pathways in Ang II-treated rats. Rats were treated for 2 wk with Ang II infusion (700 μg·kg−1·d−1; n = 6, via osmotic minipumps), Ang II plus GTE (6 g/L) dissolved in the drinking water; n = 6), or vehicle (n = 6) to serve as controls. Blood pressure was monitored by telemetry throughout the study. The activation and expression of NAD(P)H oxidase subunits, protein kinase C isoforms, Src, epidermal growth factor receptor (EGFR), Akt, and MAPK were determined in the heart in vitro through immunoprecipitation and western blot analysis with specific antibodies. NAD(P)H oxidase enzymatic activity was measured by cytochrome c reduction assay. GTE blunted Ang II-induced blood pressure increase and cardiac hypertrophy. In Ang II-treated rats, GTE decreased the expression of the NAD(P)H oxidase subunit gp91phox and the translocation of Rac-1, as well as NAD(P)H oxidase enzymatic activity. Furthermore, it specifically reduced Ang II-induced Src, EGFR, and Akt phosphorylation. These results show that GTE blunts Ang II-induced cardiac hypertrophy specifically by regulating ROS production and the Src/EGFR/Akt signaling pathway activated by Ang II.

Preventing Left Ventricular Hypertrophy by ACE Inhibition in Hypertensive Patients With Type 2 Diabetes

OBJECTIVE—In patients with type 2 diabetes, left ventricular hypertrophy (LVH) predicts cardiovascular events, and the prevention of LVH is cardioprotective. We sought to compare the effect of ACE versus non-ACE inhibitor therapy on incident electrocardiographic (ECG) evidence of LVH (ECG-LVH).RESEARCH DESIGN AND METHODS—This prespecified study compared the incidence of ECG-LVH by Sokolow-Lyon and Cornell voltage criteria in 816 hypertensive type 2 diabetic patients of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT), who had no ECG-LVH at baseline and were randomly assigned to at least 3 years of blinded ACE inhibition with trandolapril (2 mg/day) or to non-ACE inhibitor therapy. Treatment was titrated to systolic/diastolic blood pressure <130/80 mmHg. ECG readings were centralized and blinded to treatment.RESULTS—Baseline characteristics of the two groups were similar. Over a median (interquartile range) follow-up of 36 (24–48) months, 13 of the 423 patients (3.1%) receiving trandolapril compared with 31 of the 376 patients (8.2%) receiving non-ACE inhibitor therapy developed ECG-LVH (hazard ratio [HR] 0.34 [95% CI 0.18–0.65], P = 0.0012 unadjusted, and 0.35 [0.18–0.68], P = 0.0018 adjusted for predefined baseline covariates). The HR was significant even after adjustment for follow-up blood pressure and blood pressure reduction versus baseline. Compared with baseline, both Sokolow-Lyon and Cornell voltages significantly decreased with trandolapril but did not change with non-ACE inhibitor therapy.CONCLUSIONS—ACE inhibition has a specific protective effect against the development of ECG-LVH that is additional to its blood pressure–lowering effect. Because ECG-LVH is a strong cardiovascular risk factor in people with hypertension and diabetes, early ACE inhibition may be cardioprotective in this population.

Estrogen delays the progression of salt-induced cardiac hypertrophy by influencing the renin-angiotensin system in heterozygous proANP gene-disrupted mice

Left ventricular hypertrophy is considered an independent risk factor for cardiac morbidity and mortality, and many studies have shown that women have a lower incidence of left ventricular hypertrophy even after correcting for numerous risk factors. This cardio-protective effect seen in women has been attributed to estrogen, which likely modulates specific growth-promoting systems such as the renin-angiotensin system, and in turn may lead to the prevention of left ventricular hypertrophy. Furthermore, the underlying mechanisms responsible are poorly understood. The aim of the present study was to examine the effect of estrogen in relation to its impact on the development of left ventricular hypertrophy through its interaction with the renin-angiotensin system by using the proANP heterozygous (ANP +/-) mouse as a model of salt-sensitive cardiac hypertrophy. Male, female ANP +/- mice and also ovariectomized female ANP +/- mice treated with oil or estrogen, were fed either a normal or high-salt diet. All four groups exhibited a general suppression of the renin-angiotensin system under the high salt challenge. However, after the 5-week treatment period, marked left ventricular hypertrophy was noted only in the male and oil-injected ovariectomized female ANP +/- mice treated with high salt. Collectively, we provide direct evidence that the differences in cardiac hypertrophy between genders in ANP +/- mice is attributed to estrogen. Furthermore, estrogen may play a key role in slowing down the progression of salt-induced left ventricular hypertrophy in ANP +/- mice, in part, independent of the classical systemic renin-angiotensin system and possibly through other pathways.

Containing Hypertrophy With a PICOT Fence

See related article, pages 307–314 Cardiac hypertrophy is the common myocardial response to chronic hemodynamic overload. It currently affects nearly 5 million Americans and is responsible for &50 000 deaths annually. From the perspective of cardiac mechanics, it seems surprising that cardiac hypertrophy is a killer. The physics of reactive hypertrophy date to the 19th century1 and predict that hypertrophy will compensate for increased hemodynamic loading through normalization of ventricular wall stress, the phylogenetically conserved set point for cardiac load.2 The Laplace relationship (stress=½ pr/h), describes wall stress increasing in direct proportion with intraluminal pressure (p) and chamber radius (r), but decreasing as wall thickness (h) grows. Accordingly, whether the ventricle dilates or is subjected to increased pressure, hypertrophic thickening of its walls should compensate.3 And it does. However, long-term functional compensation relies on the quality of hypertrophied myocardium being invariant as quantity increases, which is not the case. Multiple studies have defined molecular, cellular, and functional characteristics of reactive hypertrophy that differentiate it from normal myocardium and from cardiac enlargement caused by physiological conditioning.4–6 Such findings gave rise to the notions of pathological and physiological hypertrophies7 and provide a mechanistic framework for why reactive hypertrophy ultimately fails,8 whereas physiological conditioning of the heart does not. Cardiac hypertrophy also has effects unrelated to contractility and ventricular ejection performance. To quote Joseph Stalin out of context, “Quantity has a quality all its own”, meaning that a steady quantitative change can create a sudden qualitative shift. The heart aptly demonstrates this principle because reactive hypertrophy and wall thickening increase ventricular stiffness, which leads to diastolic dysfunction and heart failure with preserved ejection fraction.9 Moreover, a number of studies have suggested that cardiac hypertrophy is not essential to …

Comparative Study of the Effects of Lacidipine and Enalapril on the Left Ventricular Cardiomyocyte Remodeling in Spontaneously Hypertensive Rats

Antihypertensive medications are the most efficient drugs in achieving regression of myocardial hypertrophy in both clinical studies and animal models of hypertension. Nevertheless, there is a lack of clear and concise comparative study of their effects on the modulation of cardiomyocyte morphology and function. Here, we assessed the tissue-protective actions of 2 of these drugs, the calcium channel blocker lacidipine (3 mg/kg/day) and the angiotensin-converting enzyme-inhibitor enalapril (10 mg/kg/day) in vivo, after 8 weeks of treatment of 12-week-old spontaneously hypertensive rats, as well as in vitro, after short-term (4 min) application to isolated cardiomyocytes. Left ventricular hypertrophy (LVH) was compared at organ, tissue, and single-cell level. Our data showed that both drugs prevented the LVH of 20-week-old spontaneously hypertensive rats, but only lacidipine significantly decreased the cardiomyocyte size. Similarly, the single-cell contractility was significantly lowered in lacidipine-treated rats only. The effect of lacidipine was initiated shortly after exposure to the drug in a dose-dependent manner at 0.5 Hz, as well as at 2 Hz, with EC(50) of 10(-7) mol/L. These results can help in understanding the effects of these drugs on the prevention of LVH.

Effects of Optimized Heart Failure Therapy and Anemia Correction with Epoetin β on Left Ventricular Mass in Hemodialysis Patients

Background: In chronic hemodialysis (HD) patients, the presence and degree of left ventricular hypertrophy (LVH) correlates with mortality. Previous studies have shown that interventions, such as anemia correction or treatment of hypertension and/or chronic heart failure (CHF), can result in moderate regression of LVH. The primary objective of our study was to investigate the effects of a multi-interventional treatment strategy on LVH in HD patients. Methods and Results: In a series of 202 consecutive HD patients, we combined optimized CHF therapy, including β-blockers (BB), ACE inhibitors and angiotensin receptor blockers (ARBs), to target doses with full anemia correction by epoetin β (hemoglobin (Hb) target males 14.5 g/dl, females 13.5 g/dl). Serial echocardiograms were recorded every 3–6 months. Mean follow-up was 3.4 ± 1.2 years. Mean Hb at baseline was 11.4 ± 1.4 vs. 14.6 ± 1.6 g/dl (p < 0.001) at study end. There was a significant reduction in left ventricular mass index (LVMI, 159 ± 65 vs. 132 ± 46 g/m² (p < 0.001)), an improvement in left ventricular ejection fraction (LVEF, 60 ± 15 vs. 66 ± 12% (p < 0.01)) and in NYHA class (2.8 ± 0.76 vs. 1.96 ± 0.76 (p < 0.01)) from baseline to follow-up in the overall study population. In a subgroup of 70 patients, LVMI returned to normal (169 ± 33 vs. 114 ± 14 g/m² (p < 0.001)) after 1.4 ± 1 years. Conclusions: Our study shows that optimized CHF therapy, in combination with anemia correction to normal Hb targets, results in a significant reduction of LVH, an increase in LVEF and an improvement in NYHA class. Moreover, in contrast to previous studies, our data also demonstrate that complete regression and prevention of LVH in HD patients is possible.

Cardiac hypertrophy in hypertension: relation to 24-h blood pressure profile and arterial stiffness

Background: In subjects with essential hypertension peripheral blood pressure profile contributes to the pathogenesis of left ventricular hypertrophy. It is not known if central arterial pressure is superior to peripheral blood pressure profile for predicting left ventricular hypertrophy. In the present study 24-h blood pressure profile and central hemodynamics were examined to evaluate mechanical loading factors as determinants of cardiac hypertrophy in mild to moderate untreated essential hypertension. Methods: Forty-eight untreated subjects with mild to moderate essential hypertension were examined by echocardiography for evaluation of left ventricular mass, 24-h ambulatory blood pressure monitoring (ABPM), and applanation tonometry of the radial artery with pulse wave analysis for evaluation of central hemodynamics. Results: Left ventricular mass showed a statistically significant correlation with age, clinic systolic blood pressure, mean heart rate and heart rate variability during 24-h ABPM, augmentation pressure and index and central systolic blood pressure. In a multiple regression analysis including clinic systolic blood pressure, central systolic pressure, mean systolic pressure and pulse pressure during ambulatory monitoring as well as age, independent predictors of left ventricular mass were only age ( P=0.006) and central systolic blood pressure ( P=0.04). In conclusion, pulse wave analysis is a valuable method in predicting cardiac hypertrophy in untreated mild to moderate essential hypertension. Central systolic blood pressure should be taken into account for planning therapeutic strategies for prevention of left ventricular hypertrophy in hypertensive patients.