Relation of duration of morbid obesity to left ventricular mass, systolic function, and diastolic filling, and effect of weight loss

Alpert, Martin A.; Lambert, Charles R.; Panayiotou, Hercules; Terry, Boyd E.; Cohen, Michael V.; Massey, Clara V.; Hashimi, M.Wail; Mukerji, Vaskar

doi:10.1016/s0002-9149(99)80338-5

Cited by 247 publications

(186 citation statements)

References 12 publications

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“…14,45,46 The contribution of the extracellular matrix to LVM is largely unknown, especially in the absence of left ventricular hypertrophy or hypertension. 47 ). Finally, in this study, a serum marker of myocardial fibrosis was more accurate than some echographic parameters in the discrimination of severe myocardial fibrosis from nonsevere myocardial fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Myocardial collagen turnover in normotensive obese patients: relation to insulin resistance

et al. 2005

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OBJECTIVES:The present study was undertaken to assess the differential impact of insulin resistance, leptin and body composition on myocardial mass and serum markers of cardiac fibrosis in obese subjects, within a small range of elevated BMI (30-40 kg/m 2 ), without pulmonary disease, cardiovascular disease, hypertension, cardiac hypertrophy or other cardiovascular disease. BACKGROUND: Obesity is an independent predictor of left ventricular mass (LVM) and is associated with disturbances in cardiac structure. The extent of the interstitial fibrosis in obese patients is not known, especially in the absence of cardiac hypertrophy. METHODS AND RESULTS:We included 160 obese subjects. The LVM was obtained using the Devereux formula. Body composition was estimated from a total body scan. Insulin sensitivity was assessed by homeostasis model assessment (HOMA), and cardiac collagen turnover by measurement of procollagen type III aminopeptide (PIIINP). PIIINP was correlated to the E/A ratio (r ¼ 0.24; P ¼ 0.012), a marker of ventricular function. PIIINP was independently correlated with glucose concentration (r ¼ 0.27; P ¼ 0.004), indexes of insulin resistance (HOMA (r ¼ 0.27; P ¼ 0.003), insulin (r ¼ 0.24; P ¼ 0.008)), and parameters associated with the insulin-resistance syndrome (HDL-cholesterol r ¼ À0.27; P ¼ 0.004) and fat trunk/fat leg ratio (r ¼ 0.24; P ¼ 0.053)). The variable most correlated with PIIINP was HDL-cholesterol, followed by HOMA (r 2 ¼ 0.13). When HOMA was substituted for blood glucose concentration and insulinemia (Model 2), HDL-cholesterol was strongly related to lower PIIINP levels, followed by higher glucose concentration (r 2 ¼ 0.21). Regression analyses showed that LVM had the strongest independent positive correlation with fat-free mass (FFM) (r ¼ 0.39; P ¼ 0.0002), followed by systolic blood pressure (r ¼ 0.19; P ¼ 0.034). Neither adipose mass nor height independently added information to multivariate models. The ratio leptin/fat mass was correlated with LVM (r ¼ À0.27; P ¼ 0.004), but not independently of the FFM. Markers for fibrosis were not significantly correlated with LVM. As a result, FFM was the most predictive factor of LVM in obese subjects. CONCLUSION: We found that serum levels of markers of cardiac collagen synthesis were significantly associated with insulin resistance in normotensive, nondiabetic obese subjects, and not related to the LVM. As a result, PIIINP could be a very early marker of ventricular dysfunction in these patients. Furthermore, we suggest that, for better detection of left ventricle hypertrophy in obese subjects, LVM should be indexed to FFM rather than to body surface area, or height.

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Section: Discussionmentioning

confidence: 99%

Myocardial collagen turnover in normotensive obese patients: relation to insulin resistance

et al. 2005

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“…Whereas, remodeling in pressure overload states includes a slower progression to cardiac fibrosis, specifically interstial fibrillar collagen deposition, resulting in dysfunctional chamber filling during diastole [6]. The connection between obesity and cardiovascular disease is well-established and is supported by numerous epidemiological studies [7,8]. In addition, circulating levels of the adipocyte-derived hormone leptin are positively correlated with cardiovascular complications in obese individuals and leptin may serve as a causative link [2].…”

Section: Introductionmentioning

confidence: 99%

Leptin regulates MMP-2, TIMP-1 and collagen synthesis via p38 MAPK in HL-1 murine cardiomyocytes

Schram

Girolamo

Madani

et al. 2010

Cellular and Molecular Biology Letters

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Abbreviations used: AP-1 -activator protein-1; ATF-2 -activating transcription factor-2; ECM -extracellular matrix; HF-heart failure; LV -left ventricular; MAPK -mitogen activated protein kinase; MMP -matrix metalloproteinase; mRNA-messenger ribonucleic acid; PBS -phosphate buffered saline; PCR -polymerase chain reaction; TIMP-tissue inhibitor of metalloproteinase Abstract: A clear association between obesity and heart failure exists and a significant role for leptin, the product of the obese gene, has been suggested. One aspect of myocardial remodeling which characterizes heart failure is a disruption in the balance of extracellular matrix synthesis and degradation. Here we investigated the effects of leptin on matrix metalloproteinase (MMP) activity, tissue inhibitor of metalloproteinase (TIMP) expression, as well as collagen synthesis in HL-1 cardiac muscle cells. Gelatin zymographic analysis of MMP activity in conditioned media showed that leptin enhanced MMP-2 activity in a dose-and time-dependent manner. Leptin is known to stimulate phosphorylation of p38 MAPK in cardiac cells and utilization of the p38 MAPK inhibitor, SB203580, demonstrated that this kinase also plays a role in regulating several extracellular matrix components, such that inhibition of p38 MAPK signaling prevented the leptin-induced increase in MMP-2 activation. We also observed that leptin enhanced collagen synthesis determined by both proline incorporation and picrosirius red staining of conditioned media. Pro-collagen type-I and pro-collagen type-III expression, measured by real-time PCR and Western blotting were also increased by leptin, effects which were again attenuated by SB203580. In summary, these results demonstrate the potential for leptin to play a role in mediating myocardial ECM remodeling and that the p38 MAPK pathway plays an important role in mediating these effects.

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“…2,3 Over time, MO results in structural myocardial changes, including increased left ventricular (LV) dimensions and mass, and impaired LV relaxation and systolic function. 4,5 The mechanisms underlying these changes remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Bariatric Surgery in Morbidly Obese Patients with Severe Systolic Heart Failure

Ramani

McCloskey

Ramanathan

et al. 2008

Clinical Cardiology

103

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Background: Morbid obesity (MO) is a risk factor for congestive heart failure (CHF). The presence of MO impairs functional status and disqualifies patients for cardiac transplantation. Bariatric surgery (BAS) is a frontline, durable treatment for MO; however, the safety and efficacy of BAS in advanced CHF is unknown. Hypothesis: We hypothesized that by utilizing a coordinated approach between an experienced surgical team and heart failure specialists, BAS is safe in patients with advanced systolic CHF and results in favorable outcomes. Methods: We performed a retrospective chart review of 12 patients with MO (body mass index [BMI] 53±7 kg/m 2 ) and systolic CHF (left ventricular ejection fraction [LVEF] 22±7%, New York Heart Association [NYHA] class 2.9±0.7) who underwent BAS, and then compared outcomes with 10 matched controls (BMI 47.2±3.6 kg/m 2 , LVEF 24±7%, and NYHA class 2.4±0.7) who were given diet and exercise counseling. Results: At 1 y, hospital readmission in BAS patients was significantly lower than controls (0.4±0.8 versus 2.5±2.6, p = 0.04); LVEF improved significantly in BAS patients (35±15%, p = 0.005), but not in controls (29±14%, p = not significant [NS]). The NYHA class improved in BAS patients (2.3±0.5, p = 0.02), but deteriorated in controls (3.3±0.9, p = 0.02). One BAS patient was successfully transplanted, and another listed for transplantation. Conclusions: Bariatric surgery is safe and effective in patients with MO and severe systolic CHF, and should be considered in patients who have failed conventional therapy to improve clinical status.

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Relation of duration of morbid obesity to left ventricular mass, systolic function, and diastolic filling, and effect of weight loss

Cited by 247 publications

References 12 publications

Myocardial collagen turnover in normotensive obese patients: relation to insulin resistance

Myocardial collagen turnover in normotensive obese patients: relation to insulin resistance

Leptin regulates MMP-2, TIMP-1 and collagen synthesis via p38 MAPK in HL-1 murine cardiomyocytes

Safety and Efficacy of Bariatric Surgery in Morbidly Obese Patients with Severe Systolic Heart Failure

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