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      Assessment of serum leptin, pregnancy-associated plasma protein A and CRP levels as indicators of plaque vulnerability in patients with acute coronary syndrome

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          Abstract

          Introduction

          A multifactorial aetiology of coronary artery disease (CAD) has been established in the recent past. Extensive research is now underway to understand the mechanisms responsible for plaque vulnerability. The identification of a novel biomarker that will help in the assessment of plaque status is urgently needed for the purpose of patient stratification and prognostication. The aim of the present study was to evaluate leptin, pregnancy-associated plasma protein A (PAPP-A) and C-reactive protein (CRP) levels in patients with acute coronary syndrome and to assess their diagnostic efficacy in the identification of vulnerable plaques.

          Methods

          The study group comprised 105 patients who had chest pain along with ECG changes (ST elevation, ST depression, T inversion) and raised cardiac enzyme levels. Sixty-two patients with chest pain and ECG changes but with normal cardiac enzyme profiles were included in the control group. Lipid profiles, and leptin, PAPP-A and CRP levels were assessed in these two groups. Receiver operating characteristics (ROC) curves were plotted to determine the utility of the parameters under study as markers of plaque vulnerability.

          Results

          Significantly higher levels of serum lipoprotein (a), leptin, PAPP-A and high-sensitivity CRP (hs-CRP) were observed in the cases than in the controls. A positive correlation was observed between CRP and PAPP-A levels as well as CRP and leptin concentrations. ROC curve analysis revealed similar efficacies of CRP and PAPP-A levels in their ability to detect unstable plaques with areas under the curve of 0.762 and 0.732, respectively. Multivariate analysis established the superiority of hs-CRP as a predictor of plaque instability.

          Conclusions

          Our study highlights the utility of both CRP and PAPP-A levels as determinants of plaque instability. Our findings necessitate population-based follow-up studies to establish the superiority of either of the two biomarkers in the field of preventive cardiology.

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          Most cited references52

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          Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study

          The Lancet, 349(9064), 1498-1504
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            Mechanical factors in arterial aging: a clinical perspective.

            The human arterial system in youth is beautifully designed for its role of receiving spurts of blood from the left ventricle and distributing this as steady flow through peripheral capillaries. Central to such design is "tuning" of the heart to arterial tree; this minimizes aortic pressure fluctuations and confines flow pulsations to the larger arteries. With aging, repetitive pulsations (some 30 million/year) cause fatigue and fracture of elastin lamellae of central arteries, causing them to stiffen (and dilate), so that reflections return earlier to the heart; in consequence, aortic systolic pressure rises, diastolic pressure falls, and pulsations of flow extend further into smaller vessels of vasodilated organs (notably the brain and kidney). Stiffening leads to increased left ventricular (LV) load with hypertrophy, decreased capacity for myocardial perfusion, and increased stresses on small arterial vessels, particularly of brain and kidney. Clinical manifestations are a result of diastolic LV dysfunction with dyspnea, predisposition to angina, and heart failure, and small vessel degeneration in brain and kidney with intellectual deterioration and renal failure. While aortic stiffening is the principal cause of cardiovascular disease with age in persons who escape atherosclerotic complications, it is not a specific target for therapy. The principal target is the smooth muscle in distributing arteries, whose relaxation has little effect on peripheral resistance but causes substantial reduction in the magnitude of wave reflection. Such relaxation is achieved through regular exercise and with the vasodilating drugs that are used in modern treatment of hypertension and cardiac failure.
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              Leptin regulates proinflammatory immune responses.

              Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality. Decreased expression of leptin or of functional leptin receptors results in hyperphagia, decreased energy expenditure, and obesity. It is unclear, however, whether defective leptin-dependent signal transduction directly promotes any of the conditions that frequently complicate obesity. Abnormalities in tumor necrosis factor alpha expression have been noted in each of the above comorbid conditions, so leptin deficiency could promote these complications if leptin had immunoregulatory activity. Studies of rodents with genetic abnormalities in leptin or leptin receptors revealed obesity-related deficits in macrophage phagocytosis and the expression of proinflammatory cytokines both in vivo and in vitro. Exogenous leptin up-regulated both phagocytosis and the production of proinflammatory cytokines. These results identify an important and novel function for leptin: up-regulation of inflammatory immune responses, which may provide a common pathogenetic mechanism that contributes to several of the major complications of obesity.
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                Author and article information

                Contributors
                Journal
                Cardiovasc J Afr
                Cardiovasc J Afr
                TBC
                Cardiovascular Journal of Africa
                Clinics Cardive Publishing
                1995-1892
                1680-0745
                July 2012
                : 23
                : 6
                : 330-335
                Affiliations
                Department of Biochemistry, The Mission Hospital, Durgapur, West Bengal, India
                Department of Biochemistry, GB Pant Hospital, New Delhi, India
                Department of Cardiology, The Mission Hospital, Durgapur, West Bengal, India
                Department of Biochemistry, Lady Hardinge Medical College and associated hospitals, New Delhi, India
                Department of Biochemistry, Maulana Azad Medical College and associated hospitals, New Delhi, India
                Article
                10.5830/CVJA-2012-008
                3734746
                22836155
                71a4539c-7f9a-4fb6-aa00-544d34bacfbd
                Copyright © 2010 Clinics Cardive Publishing

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 February 2011
                : 8 February 2012
                Categories
                Cardiovascular Topics

                leptin,hs-crp,papp-a,metalloproteinase,plaque rupture
                leptin, hs-crp, papp-a, metalloproteinase, plaque rupture

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