Pathogenesis Of Left Ventricular Hypertrophy Research Articles

Antagonizing the CX3CR1 Receptor Markedly Reduces Development of Cardiac Hypertrophy After Transverse Aortic Constriction in Mice.

Left-ventricular hypertrophy, characterized by cardiomyocyte hypertrophy, interstitial cell proliferation, and immune cell infiltration, is a high risk factor for heart failure and death. Chemokines interacting with G protein-coupled chemokine receptors probably play a role in left-ventricular hypertrophy development by promoting recruitment of activated leukocytes and modulating left-ventricular remodeling. Using the minimally invasive model of transverse aortic constriction in mice, we demonstrated that a variety of chemokine and chemokine receptor messenger Ribonucleic Acid are overexpressed in the early and late phase of hypertrophy progression. Among the chemokine receptors, Cx3cr1 and Ccr2 were most strongly overexpressed and were significantly upregulated at 3, 7, and 14 days after transverse aortic constriction. Ligands of CX3CR1 (Cx3cl1) and CCR2 (Ccl2, Ccl7, Ccl12) were significantly overexpressed in the left ventricle at the early stages after mechanical pressure overload. Pharmacological inhibition of CX3CR1 signaling using the antagonist AZD8797 led to a significant reduction of hypertrophy, whereas inhibition of CCR2 with the RS504393 antagonist did not show any effect. Furthermore, AZD8797 treatment reduced the expression of the hypertrophic marker genes Nppa and Nppb as well as the profibrotic genes Tgfb1 and Col1a1 at 14 days after transverse aortic constriction. These findings strongly suggest the involvement of the CX3CR1/CX3CL1 pathway in the pathogenesis of left-ventricular hypertrophy.

Interleukin 18 as a new inflammatory mediator in left ventricular hypertrophy in children with end-stage renal disease.

Left ventricular hypertrophy (LVH) represents an important determinant of increased cardiovascular morbidity and mortality (CV) in end-stage renal disease (ESRD) patients. The role of inflammatory markers in pathogenesis of LVH in children with ESRD is not fully described. The aim of this study is to evaluate relation of some inflammatory markers [as hs C-reactive protein (hsCRP) and interleukin (IL) 18] with LVH in children with ESRD on regular hemodialysis (HD). This is a cross-sectional study performed on 50 children on regular HD. Demographic data were recorded. Echocardiography was performed at baseline to determine those with LVH. Biochemical parameters: hemoglobin (HB), hsCRP, IL 18, phosphorus, calcium, serum albumin, and lipid profile were evaluated and correlated with LVH. Data were analyzed using Student's t-test, and logistic regression to determine the relationship between LVH and other variables. LVH was present in 33 (66%) participants. Mean left ventricular mass index was 56.88 ± 22.23 g/m.2.7 Concentric remodeling, concentric hypertrophy, and eccentric hypertrophy were present in 4%, 22%, and 44% of the participants. In univariate analysis, children with LVH had significantly lower levels of HB and serum albumin but higher levels of hsCRP, and IL 18 compared to those without LVH. On multivariate analysis: only hsCRP, and IL 18 were significantly associated with LVH. This study shows that elevated hsCRP and IL-18 are independent determinants of LVH in HD children. Understanding the role of inflammatory molecules in the pathogenesis of LVH in ESRD is important for prediction of high-risk group and implementation of targeted anti-inflammatory therapies.

Resveratrol Suppresses Cardiac Renin Angiotensin System in the Late Phase of Left Ventricular Hypertrophy

Background and objectives: Resveratrol(3,5,4′-trihydroxy-trans-stilbene) is a natural polyphenole phytoalexin which exerts potential cardioprotective effects, but the cellular and molecular mechanisms responsible for these effects are still unknown. Cardiac renin angiotensin system (RAS) over-activation plays an important role in pathogenesis of left ventricular hypertrophy (LVH) progression. The aim of the study was to investigate the effects of resveratrol on the main components of RAS during early and late phase of myocardial hypertrophy. Methods: To consider the early and late phase of LVH, the rats were studied two and sixteen weeks after abdominal aorta banding without treatment (H2w and H16w groups, respectively) or with resveratrol (R) treatment. Intact animals served as control (Ctl). Arterial blood pressure was recorded by carotid cannulation. Angiotensin II (Ang II) level was measured using ELISA kit. Gene expression was evaluated by Real time RT-PCR technique. Cardiomyocyte size and fibrosis were assessed using haematoxylin/eosin and Masson trichrome staining, respectively Results: Results of this study showed that in H2w group AT1a mRNA level was increased significantly (pConclusion: Progression of LVH is accompanied by dynamic changes in RAS components expression in myocardial tissue. Resveratrol protects the heart against pressure overload-induced hypertrophy in part via RAS suppression.

Cardiovascular Interactions between Fibroblast Growth Factor-23 and Angiotensin II

Both the activation of the renin angiotensin aldosterone system (RAAS) and elevations of circulating Fibroblast Growth Factor-23 (FGF-23) have been implicated in the pathogenesis of left ventricular hypertrophy (LVH) in chronic kidney disease. To investigate potential cross-talk between RAAS and FGF-23, we administered angiotensin II (Ang II) to wild-type rodents and the Hyp mouse model of excess FGF-23. Ang II administration for four weeks to wild-type rodents resulted in significant increases in systolic blood pressure and LVH. Unexpectedly, FGF-23 circulating levels were increased by 1.5–1.7 fold in Ang II treated animals. In addition, Ang II treatment increased expression of FGF-23 message levels in bone, the predominant tissue for FGF-23 production, and induced expression of FGF-23 and its co-receptor α-Klotho in the heart, which normally does not express FGF-23 or α-Klotho in physiologically relevant levels. Hyp mice with elevated FGF-23 exhibited increased blood pressure and LVH at baseline. Ang II administration to Hyp mice resulted further increments in blood pressure and left ventricular hypertrophy, consistent with additive cardiovascular effects. These findings suggest that FGF-23 may participate in unexpected systemic and paracrine networks regulating hemodynamic and myocardial responses.

Zmiany w EKG o charakterze przerostu lewej komory z zaburzeniami repolaryzacji – możliwe trudności diagnostyczne na podstawie opisu przypadku

Electrocardiographic changes of the nature of left ventricular hypertrophy with repolarization abnormalities may cause some diagnostic difficulties in the outpatient setting resulting from the etiology of changes. Chronic kidney disease (CKD) is a global public health problem that shortens lifespan, primarily by increasing risk of cardiovascular disease. Left ventricular hypertrophy (LVH) is a common pattern of cardiovascular injury in CKD that affects up to 75% of individuals by the time they reach end-stage renal disease. By promoting heart failure and atrial and ventricular arrhythmias, LVH is a powerful risk factor for cardiovascular events and death. The complex pathogenesis of LVH involves ventricular pressure and volume overload and the electrocardiographic record alone may sometimes suggest suspicion of an acute coronary syndrome. In this paper, we describe the case of a 39-year-old patient who was referred to the Cardiology Clinic with a preliminary diagnosis of „infarctus myocardia in evolution”, however, the final diagnosis was chronic kidney disease in stage 5 on a base of hypertensive nephropathy (not biopsy proven).

Skin Sodium Concentration Correlates with Left Ventricular Hypertrophy in CKD.

The pathogenesis of left ventricular hypertrophy in patients with CKD is incompletely understood. Sodium intake, which is usually assessed by measuring urinary sodium excretion, has been inconsistently linked with left ventricular hypertrophy. However, tissues such as skin and muscle may store sodium. Using 23sodium-magnetic resonance imaging, a technique recently developed for the assessment of tissue sodium content in humans, we determined skin sodium content at the level of the calf in 99 patients with mild to moderate CKD (42 women; median [range] age, 65 [23-78] years). We also assessed total body overhydration (bioimpedance spectroscopy), 24-hour BP, and left ventricular mass (cardiac magnetic resonance imaging). Skin sodium content, but not total body overhydration, correlated with systolic BP (r=0.33, P=0.002). Moreover, skin sodium content correlated more strongly than total body overhydration did with left ventricular mass (r=0.56, P<0.001 versus r=0.35, P<0.001; P<0.01 between the two correlations). Linear regression analysis demonstrated that skin sodium content is a strong explanatory variable for left ventricular mass, unaffected by BP and total body overhydration. In conclusion, we found skin sodium content to be closely linked to left ventricular mass in patients with CKD. Interventions that reduce skin sodium content might improve cardiovascular outcomes in these patients.

Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction.

The role of interleukin (IL)-6 in the pathogenesis of cardiac myocyte hypertrophy remains controversial. To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy and to elucidate the underlying molecular pathways. Wild-type and IL-6 knockout (IL-6(-/-)) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6(-/-) mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6(-/-) hearts after TAC. Transcriptional and protein assays of myocardial tissue identified Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and signal transducer and activator of transcription 3 (STAT3) activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiac myocytes from wild-type and IL-6(-/-) mice exposed to prohypertrophy agents. Furthermore, overexpression of CaMKII in H9c2 cells increased STAT3 phosphorylation, and exposure of H9c2 cells to IL-6 resulted in STAT3 activation that was attenuated by CaMKII inhibition. Together, these results identify the importance of CaMKII-dependent activation of STAT3 during cardiac myocyte hypertrophy via IL-6 signaling. Genetic deletion of IL-6 attenuates TAC-induced LV hypertrophy and dysfunction, indicating a critical role played by IL-6 in the pathogenesis of LV hypertrophy in response to pressure overload. CaMKII plays an important role in IL-6-induced STAT3 activation and consequent cardiac myocyte hypertrophy. These findings may have significant therapeutic implications for LV hypertrophy and failure in patients with hypertension.

Where is the link between mineral bone markers and cardiovascular disease in CKD?

Where is the link between mineral bone markers and cardiovascular disease in CKD?

A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy.

Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 ± 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) ≥40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7%) and myocardial infarction (n = 545; 54.1%) with a mean LVEF of 59.9% ± 9.3%. The mean left ventricular mass index (LVMI) was 52.1 ± 21.2 g/m2.7 and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%–12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition.

Mitochondria: a pathogenic paradigm in hypertensive renal disease.

Mitochondria were first described in 1840 as bioblasts, elementary organisms responsible for vital cellular functions, but were subsequently named mitochondria, from the Greek names mitos (thread) and chondros (granule), which describes their appearance during spermatogenesis.1 Their discovery generated substantial interest given their structure resembling bacteria, which led in subsequent years to important scientific discoveries positioning mitochondria as the energy powerhouse of the cell. The unique architecture of mitochondria, consisting of 2 membranes (outer and inner) and compartments (intermembrane space and matrix), is crucial for their vital functions. Mitochondria serve not only as primary sources of cellular energy, but also modulate several cellular processes, including oxidative phosphorylation, calcium homeostasis, thermogenesis, oxygen sensing, proliferation, and apoptosis.2 Therefore, mitochondrial injury and dysfunction might be implicated in the pathogenesis of several diseases. Hypertension accounts for nearly 30% of patients reaching end-stage renal disease.3 Renal injury secondary to hypertension or to ischemia associated with renovascular hypertension (distal to renal artery stenosis) may have significant and detrimental effect on health outcomes. Studies have highlighted several deleterious pathways, including inflammation, oxidative stress, and fibrosis that are activated in the hypertensive kidney, eliciting functional decline.4,5 However, the precise molecular mechanisms responsible for renal injury have not been fully elucidated. Over the past few years, increasing evidence has established the experimental foundations linking mitochondrial alterations to hypertensive renal injury (Table). Mitochondriopathies, abnormalities of energy metabolism secondary to sporadic or inherited mutations in nuclear or mitochondrial DNA (mtDNA) genes, may contribute to the development and progression of hypertension and its complications. In addition, several studies have reported mitochondrial damage and dysfunction consequent to hypertensive renal disease. View this table: Table. Evidence of Renal Mitochondrial Damage in Models of Hypertension and Antihypertensive Treatment Importantly, hypertensive-induced renal injury is characterized by activation of several deleterious pathways, including oxidative stress, renin–angiotensin–aldosterone …

Treatment of established left ventricular hypertrophy with fibroblast growth factor receptor blockade in an animal model of CKD.

Activation of fibroblast growth factor receptor (FGFR)-dependent signalling by FGF23 may contribute to the complex pathogenesis of left ventricular hypertrophy (LVH) in chronic kidney disease (CKD). Pan FGFR blockade by PD173074 prevented development of LVH in the 5/6 nephrectomy rat model of CKD, but its ability to treat and reverse established LVH is unknown. CKD was induced in rats by 5/6 nephrectomy. Two weeks later, rats began treatment with vehicle (0.9% NaCl) or PD173074, 1 mg/kg once-daily for 3 weeks. Renal function was determined by urine and blood analyses. Left ventricular (LV) structure and function were determined by echocardiography, histopathology, staining for myocardial fibrosis (Sirius-Red) and investigating cardiac gene expression profiles by real-time PCR. Two weeks after inducing CKD by 5/6 nephrectomy, rats manifested higher (mean ± SEM) systolic blood pressure (208 ± 4 versus 139 ± 3 mmHg; P < 0.01), serum FGF23 levels (1023 ± 225 versus 199 ± 9 pg/mL; P < 0.01) and LV mass (292 ± 9 versus 220 ± 3 mg; P < 0.01) when compared with sham-operated animals. Thereafter, 3 weeks of treatment with PD173074 compared with vehicle did not significantly change blood pressure, kidney function or metabolic parameters, but significantly reduced LV mass (230 ± 14 versus 341 ± 33 mg; P < 0.01), myocardial fibrosis (2.5 ± 0.7 versus 5.4 ± 0.95% staining/field; P < 0.01) and cardiac expression of genes associated with pathological LVH, while significantly increasing ejection fraction (18 versus 2.5% post-treatment increase; P < 0.05). FGFR blockade improved cardiac structure and function in 5/6 nephrectomy rats with previously established LVH. These data support FGFR activation as a potentially modifiable, blood pressure-independent molecular mechanism of LVH in CKD.

Increased circulating endothelial cells in patients with hypertrophic cardiomyopathy: correlation with left ventricular mass index

Purpose: Stem and progenitor cells are implicated in ventricular remodelling and have great clinical significance in the pathophysiology of heart failure and atheromatosis. However, there are limited data regarding the involvement of Endothelial Cells (ECs) in the pathogenesis of Left Ventricular Hypertrophy (LVH). The aim of this study is to investigate ECs circulation in patients with Hypertrophic Cardiomyopathy (HCM). Methods: We included 17 patients with HCM (10 males, aged 51±12 years) and 10 healthy individuals (6 males, aged 54±10 years). All subjects underwent a complete echocardiographic study. In addition, peripheral blood samples from all participants were immunostained with antibodies against the cell surface markers CD34, CD45, CD133. The resulting counts were translated into the % percentage of ECs in the total cell number of peripheral blood. Results: Patients with HCM were shown to have increased circulating CD45-/CD34+/CD133+ cells (0.003±0.001%), compared to control group 0.0001±0.003%), (p < 0.05 for both comparisons). CD45-/CD34+/CD133+ cell population revealed a positive correlation with left ventricular mass index ((r=0.47, p=0.002). Conclusions: Patients with HCM were shown to have increased circulating ECs compared to healthy individuals and this is correlated with the severity of LVH. Our findings contribute to the understanding of pathogenesis of HCM and might offer a future therapeutic target

Increased circulating mesencymal stem cells in patients with hypertrophic cardiomyopathy: correlation with left ventricular mass index

Purpose: Stem and progenitor cells are implicated in ventricular remodelling and have great clinical significance in the pathophysiology of heart failure and atheromatosis. However, there are limited data regarding the involvement of Endothelial Cells (ECs) in the pathogenesis of Left Ventricular Hypertrophy (LVH). The aim of this study is to investigate ECs circulation in patients with Hypertrophic Cardiomyopathy (HCM). Methods: We included 17 patients with HCM (10 males, aged 51±12 years) and 10 healthy individuals (6 males, aged 54±10 years). All subjects underwent a complete echocardiographic study. In addition, peripheral blood samples from all participants were immunostained with antibodies against the cell surface markers CD34, CD45, CD133. The resulting counts were translated into the % percentage of ECs in the total cell number of peripheral blood. Results: Patients with HCM were shown to have increased circulating CD45-/CD34+/CD133+ cells (0.003±0.001%), compared to control group 0.0001±0.003%), (p < 0.05 for both comparisons). CD45-/CD34+/CD133+ cell population revealed a positive correlation with left ventricular mass index ((r=0.47, p=0.002). Conclusions: Patients with HCM were shown to have increased circulating ECs compared to healthy individuals and this is correlated with the severity of LVH. Our findings contribute to the understanding of pathogenesis of HCM and might offer a future therapeutic target

Left ventricular hypertrophy and renin-angiotensin-aldosterone system: AT1-receptor blockers are in the focus

Left ventricular hypertrophy (LVH) is one of the cardio-vascular continuum components, determining the prognosis of patient with essential hypertension (EH). Pathogenesis of LVH has a multifactor character. Important role in development of cardiomyocites hypertrophy, Intracardiac fibrosis, left ventricle cavity dilation belongs to renin-angiotensin-aldosteron system (RAAS). Pharmacologic blockade of RAAS composes the basis of therapy, directed to LVH regress. Application of Telmisartan is considered high-reasonable approach to treatment of EH-patient with LVH.

Effect of alfacalcidol on cardiac function in patients with chronic kidney disease stage 4 and secondary hyperparathyroidism: A pilot study

Left ventricular hypertrophy (LVH) is highly prevalent in chronic kidney disease (CKD) and a risk marker for cardiovascular mortality. It was hypothesized that vitamin D deficiency could play an important role in the pathogenesis of left ventricular hypertrophy and dysfunction in CKD. An open-labelled randomized study was performed comparing the effect of alfacalcidol versus no treatment in patients with CKD 4, secondary hyperparathyroidism and LVH. The primary endpoint was regression of LVH. Secondary endpoints were changes in left ventricular function. Twenty-four patients were screened. Of these, 14 had LVH according to the criteria used. Six were randomized to alfacalcidol and seven to no treatment. The patient follow-up was 6 months. Left ventricular mass and function were measured by echocardiography. Parathyroid hormone decreased by 72% and -3% in the alfacalcidol-treated and non-treated groups, respectively (p < 0.05), while serum Ca(2+) increased by 9% and -1.6%, respectively (p < 0.05), and serum phosphate was unchanged. The left ventricular mass index was unchanged, whereas fractional shortening (20% vs 2%, p < 0.005) and Tei index (36% vs 12%, p < 0.05) increased significantly. Systolic and diastolic blood pressure was unchanged. Short-term treatment with alfacalcidol did not induce regression of LVH; however, left ventricular function became hyperdynamic but less effective in patients with CKD. This could be problematic in the long term.

FGF23 induces left ventricular hypertrophy

Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF-receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.

Erythropoiesis-stimulating agents, hypertension and left ventricular hypertrophy in the chronic kidney disease patient

Left-ventricular hypertrophy (LVH) represents an important marker of cardiovascular morbidity and mortality. Numerous noninterventional studies in patients with chronic kidney disease (CKD) revealed a consistent relationship of LVH with modifiable risk factors attributable to failing renal function, particularly anemia and hypertension. Given the clear role for anemia in initiating or accelerating LVH, it seems imperative to correct renal anemia with erythropoiesis-stimulating agents (ESAs). A few nonrandomized studies have described a regression of LVH with correction of anemia, but prospective randomized trials showed no evidence that ESA treatment is able to improve cardiac prognosis in the CKD patient. Current data alert physicians that normalization of hemoglobin in patients with advanced CKD is harmful. Recent studies are now trying to clarify the mechanisms for harm focussing on the influence of comorbidities, ESA doses, and hemoglobin variability. The pathogenesis of hypertension in CKD is multifactorial and only a small percentage of CKD patients have controlled their blood pressure, indicating poor medication adherence, insufficient control of volume overload and undertreatment. This review provides an update of ESA treatment, hypertension and LVH in the CKD patient, indicating that pathogenesis of LVH in this population is currently not completely understood. In addition, the impact of pharmacological interventions targeted to prevent or reduce LVH in anemic or hypertensive CKD patients is not well defined. As adoption of the Framingham approach seems not feasible in the CKD patient, evidence from large-scale randomized clinical trials is mandatory to resolve this dilemma.

Plasma adiponectin concentration and left ventricular hypertrophy in kidney transplant patients

Low plasma adiponectin concentration is associated with more frequent occurrence of left ventricular hypertrophy (LVH) and more exaggerated intima-media thickness of common carotid artery (IMT). IMT is an early surrogate marker of atherosclerosis. This study aimed to assess the relationship between plasma adiponectin concentration and left ventricular mass index (LVMI) and IMT in kidney transplant patients (KTP). In 88 adult KTP, plasma adiponectin concentration, LVMI, and IMT were estimated. LVH was defined as LVMI >110 or >125 g/m(2) for females and males, respectively. Data presented are means and 95% CI. Plasma adiponectin concentration was similar in KTP with (n = 42) or without LVH (n = 46) (13.5 [11.4-15.6] vs. 13.1 [11.6-14.6] μg/mL, respectively), as well as in KTP subgroups divided according to the IMT value tertiles (p = 0.42) (11.7 [10.0-13.3], 14.2 [11.7-16.6], and 14.0 [11.7-16.4] μg/mL in the lowest, middle, and highest tertiles, respectively). Plasma glucose concentrations were similar in KTPs with LVH or without LVH. No significant correlation was found between plasma adiponectin concentration and both LVMI (R = -0.02; p = 0.87) and IMT (R = 0.09; p = 0.38), respectively. Results of this cross-sectional study do not confirm the roles of low adiponectin and high glucose in the pathogenesis of LVH and atherosclerosis in KTP.

Masked Hypertension Associates with Left Ventricular Hypertrophy in Children with CKD

Left ventricular hypertrophy (LVH) associates with increased risk for cardiovascular disease. Hypertension leads to LVH in adults, but its role in the pathogenesis of LVH in children is not as well established. To examine left ventricular mass and evaluate factors associated with LVH in children with stages 2 through 4 chronic kidney disease (CKD), we analyzed cross-sectional data from children who had baseline echocardiography (n = 366) and underwent ambulatory BP monitoring (n = 226) as a part of the observational Chronic Kidney Disease in Children (CKiD) cohort study. At baseline, 17% of children had LVH (11% eccentric and 6% concentric) and 9% had concentric remodeling of the left ventricle. On the basis of a combination of ambulatory and casual BP assessment (n = 198), 38% of children had masked hypertension (normal casual but elevated ambulatory BP) and 18% had confirmed hypertension (both elevated casual and ambulatory BP). There was no significant association between LVH and kidney function. LVH was more common in children with either confirmed (34%) or masked (20%) hypertension compared with children with normal casual and ambulatory BP (8%). In multivariable analysis, masked (odds ratio 4.1) and confirmed (odds ratio 4.3) hypertension were the strongest independent predictors of LVH. In conclusion, casual BP measurements alone are insufficient to predict the presence of LVH in children with CKD. The high prevalence of masked hypertension and its association with LVH supports early echocardiography and ambulatory BP monitoring to evaluate cardiovascular risk in children with CKD.

Magnetic Resonance Imaging Left Ventricular Mass Reduction With Fixed-Dose Angiotensin-Converting Enzyme Inhibitor–Based Regimens in Patients With High-Risk Hypertension

Left ventricular hypertrophy, a major cardiovascular risk factor for morbidity and mortality, is commonly caused by arterial hypertension. The renin-angiotensin-aldosterone system may contribute to the pathogenesis of left ventricular hypertrophy. The Assessment of Lotrel in Left Ventricular Hypertrophy and Hypertension Study compared a single-pill combination of amlodipine/benazepril at doses 5.0/20.0 mg, 5.0/40.0 mg, and 10.0/40.0 mg with hydrochlorothiazide/benazepril at doses 12.5/20.0 mg, 12.5/40.0 mg, and 25.0/40.0 mg on the reduction of left ventricular mass index measured by cardiac MRI in stage 2 hypertensive patients over 52 weeks of treatment in a randomized clinical trial. A total of 125 male and female patients, > or =55 years of age, with echocardiographic left ventricular hypertrophy and high-risk hypertension defined as blood pressure > or =160/100 mm Hg or current antihypertensive treatment were enrolled. After 52 weeks of treatment, left ventricular mass index was significantly reduced from baseline with amlodipine/benazepril (mean: 10.16 g/m(2)) or hydrochlorothiazide/benazepril (mean: 6.74 g/m(2); both P<0.0001), with a mean difference between treatment groups of 3.36 g/m(2) (P=0.16). No significant treatment differences were observed in subgroups defined by age, male gender, race, diabetes status, or dose level. However, in female patients, left ventricular mass index reduction was greater with amlodipine/benazepril (P=0.02). Both treatments were well tolerated.