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      Reduced global longitudinal strain at rest and inadequate blood pressure response during exercise treadmill testing in male heterozygous familial hypercholesterolemia patients

      research-article
      a , , a , b , c , g , d , h , i , a , a , e , a , f
      International Journal of Cardiology Hypertension
      Elsevier
      Heterozygous familial hypercholesterolemia, Exercise treadmill test, Coronary artery disease, Arterial blood pressure, Global longitudinal strain, BP, blood pressure, CAD, coronary artery disease, DBP, diastolic blood pressure, EDV, end-diastolic volume, ESV, end-systolic volume, ETT, Exercise treadmill test, FH, Familial hypercholesterolemia, GLS, Global longitudinal strain, HDL, high density lipoprotein, heFH, heterozygous familial hypercholesterolemia, hoFH, homozygous familial hypercholesterolemia, HR, heart rate, LDL, low-density lipoprotein, LV, left ventricle, LVEF, LV ejection fraction, METs, metabolic equivalents, RPP, rate pressure product, SBP, systolic blood pressure, TC, total cholesterol, TG, triglyceride

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          Abstract

          Background

          Heterozygous familial hypercholesterolemia (heFH) is a genetic disorder leading to premature coronary artery disease (CAD). We hypothesized that the subclinical pathophysiologic consequences of hypercholesterolemia may be detected before the occurrence of clinically overt CAD by stress testing and myocardial strain imaging.

          Patients-methods

          We evaluated the treadmill tests (ETTs) of 46 heFH men without known arterial hypertension/diabetes mellitus/vasculopathy like CAD and of 39 healthy men matched for age, baseline systolic/diastolic blood pressure (BP) and heart rate (HR), using Bruce protocol. Global longitudinal strain (GLS) of the left ventricle (LV) additionally to ejection fraction was obtained.

          Results

          heFH men reached a significantly higher peak systolic and diastolic BP compared to controls (p = 0.002 and p < 0.001, respectively). Mean rate pressure product was significantly higher in heFH patients (p = 0.038). Both duration of the ETT and workload in metabolic equivalents was lower in the heFH group (p < 0.001 and p < 0.001, respectively). Baseline to peak rise of systolic and diastolic BP in heFH men was higher (p = 0.008 and p < 0.001 for systolic and diastolic BP, respectively). Furthermore, heFH men had higher rise of HR from baseline to peak, compared to controls; (p = 0.047). GLS in heHF men was slightly decreased (p = 0.014), although the ejection fraction was similar in both groups.

          Conclusion

          heFH men have a higher rise in systolic/diastolic BP during ETT, which may reflect early, preclinical hypertension. Furthermore, slight impairment of LV GLS is present, despite the absence of apparent myocardial dysfunction in conventional 2D echocardiography.

          Highlights

          • Stress testing and myocardial strain imaging may detect subclinical consequences of heterozygous familial hypercholesterolemia.

          • Male patients with heFH underwent exercise treadmill testing and speckle-tracking echocardiography.

          • Male heFH patients showed a higher rise in systolic/diastolic blood pressure during exercise treadmill testing than healthy controls.

          • Global longitudinal strain of heFH males is slightly impaired compared with healthy subjects.

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          Most cited references34

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          Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.

          The rapid technological developments of the past decade and the changes in echocardiographic practice brought about by these developments have resulted in the need for updated recommendations to the previously published guidelines for cardiac chamber quantification, which was the goal of the joint writing group assembled by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases. In addition, this document attempts to eliminate several minor discrepancies that existed between previously published guidelines. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
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            The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.

            Despite its very potent vasodilating action in vivo, acetylcholine (ACh) does not always produce relaxation of isolated preparations of blood vessels in vitro. For example, in the helical strip of the rabbit descending thoracic aorta, the only reported response to ACh has been graded contractions, occurring at concentrations above 0.1 muM and mediated by muscarinic receptors. Recently, we observed that in a ring preparation from the rabbit thoracic aorta, ACh produced marked relaxation at concentrations lower than those required to produce contraction (confirming an earlier report by Jelliffe). In investigating this apparent discrepancy, we discovered that the loss of relaxation of ACh in the case of the strip was the result of unintentional rubbing of its intimal surface against foreign surfaces during its preparation. If care was taken to avoid rubbing of the intimal surface during preparation, the tissue, whether ring, transverse strip or helical strip, always exhibited relaxation to ACh, and the possibility was considered that rubbing of the intimal surface had removed endothelial cells. We demonstrate here that relaxation of isolated preparations of rabbit thoracic aorta and other blood vessels by ACh requires the presence of endothelial cells, and that ACh, acting on muscarinic receptors of these cells, stimulates release of a substance(s) that causes relaxation of the vascular smooth muscle. We propose that this may be one of the principal mechanisms for ACh-induced vasodilation in vivo. Preliminary reports on some aspects of the work have been reported elsewhere.
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              Myocardial strain imaging: how useful is it in clinical decision making?

              Myocardial strain is a principle for quantification of left ventricular (LV) function which is now feasible with speckle-tracking echocardiography. The best evaluated strain parameter is global longitudinal strain (GLS) which is more sensitive than left ventricular ejection fraction (LVEF) as a measure of systolic function, and may be used to identify sub-clinical LV dysfunction in cardiomyopathies. Furthermore, GLS is recommended as routine measurement in patients undergoing chemotherapy to detect reduction in LV function prior to fall in LVEF. Intersegmental variability in timing of peak myocardial strain has been proposed as predictor of risk of ventricular arrhythmias. Strain imaging may be applied to guide placement of the LV pacing lead in patients receiving cardiac resynchronization therapy. Strain may also be used to diagnose myocardial ischaemia, but the technology is not sufficiently standardized to be recommended as a general tool for this purpose. Peak systolic left atrial strain is a promising supplementary index of LV filling pressure. The strain imaging methodology is still undergoing development, and further clinical trials are needed to determine if clinical decisions based on strain imaging result in better outcome. With this important limitation in mind, strain may be applied clinically as a supplementary diagnostic method.
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                Author and article information

                Contributors
                Journal
                Int J Cardiol Hypertens
                Int J Cardiol Hypertens
                International Journal of Cardiology Hypertension
                Elsevier
                2590-0862
                20 April 2021
                June 2021
                20 April 2021
                : 9
                : 100083
                Affiliations
                [a ]Onassis Cardiac Surgery Center, Department of Cardiology, Athens, Greece
                [b ]Harokopio University, Athens, Greece
                [c ]National and Kapodistrian University of Athens, Medical School, Greece
                [d ]Internal Medicine, National and Kapodistrian University of Athens Medical School, Greece
                [e ]Metropolitan Hospital, Athens, Greece
                [f ]National and Kapodistrian University of Athens, Division of Experimental Surgery, Greece
                [g ]Hippokration Hospital, First Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Greece
                [h ]Hellenic Diabetes Association, Athens, Greece
                [i ]Laikon Hospital, First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece
                Author notes
                []Corresponding author. Onassis Cardiac Surgery Center, 356 Syngrou Ave, Kallithea, Athens, 17674, Greece. vasvartela@ 123456yahoo.gr
                Article
                S2590-0862(21)00008-2 100083
                10.1016/j.ijchy.2021.100083
                8167294
                34095810
                bffa342a-d7f8-467b-a272-d4bb8780cbbc
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 10 February 2021
                : 1 April 2021
                : 15 April 2021
                Categories
                Research Paper

                heterozygous familial hypercholesterolemia,exercise treadmill test,coronary artery disease,arterial blood pressure,global longitudinal strain,bp, blood pressure,cad, coronary artery disease,dbp, diastolic blood pressure,edv, end-diastolic volume,esv, end-systolic volume,ett, exercise treadmill test,fh, familial hypercholesterolemia,gls, global longitudinal strain,hdl, high density lipoprotein,hefh, heterozygous familial hypercholesterolemia,hofh, homozygous familial hypercholesterolemia,hr, heart rate,ldl, low-density lipoprotein,lv, left ventricle,lvef, lv ejection fraction,mets, metabolic equivalents,rpp, rate pressure product,sbp, systolic blood pressure,tc, total cholesterol,tg, triglyceride

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