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• W2054570956 abstract "Metabolic syndrome (MS) is commonly associated with left ventricular (LV) diastolic dysfunction and LV hypertrophy. We sought to examine whether preclinical LV diastolic dysfunction can occur independent of LV hypertrophy in MS. We recruited 90 consecutive participants with MS and without cardiovascular disease (mean age 46 years, 78% women) and 26 controls (no risk factors for MS; mean age 43 years, 65% women). Participants underwent echocardiography with tissue Doppler imaging. In age- and gender-adjusted analyses, MS was associated with higher left atrial (LA) diameter, higher LV mass, lower E/A ratio, and lower mean e′ (p <0.001 for all). These associations remained significant after further adjusting for blood pressure, antihypertensive medication use, and body mass index. After adjusting for LV mass, MS remained independently associated with higher LA diameter, lower E/A ratio, and lower mean e′ (p ≤0.01 for all). Specifically, subjects with MS had a 1.8 cm/s lower mean e′ compared with controls (p = 0.01). Notably, differences in mean e′ between those with and without MS were more pronounced at younger ages (p for interaction = 0.003). In conclusion, MS was associated with preclinical LV diastolic dysfunction independent of LV mass, as reflected by higher LA diameter, lower E/A ratio, and lower mean e′. This suggests that MS can lead to the development of diastolic dysfunction through mechanisms independent of hypertrophy. Differences in diastolic function were more pronounced at younger ages, highlighting the potential importance of early risk factor modification and preventive strategies in MS. Metabolic syndrome (MS) is commonly associated with left ventricular (LV) diastolic dysfunction and LV hypertrophy. We sought to examine whether preclinical LV diastolic dysfunction can occur independent of LV hypertrophy in MS. We recruited 90 consecutive participants with MS and without cardiovascular disease (mean age 46 years, 78% women) and 26 controls (no risk factors for MS; mean age 43 years, 65% women). Participants underwent echocardiography with tissue Doppler imaging. In age- and gender-adjusted analyses, MS was associated with higher left atrial (LA) diameter, higher LV mass, lower E/A ratio, and lower mean e′ (p <0.001 for all). These associations remained significant after further adjusting for blood pressure, antihypertensive medication use, and body mass index. After adjusting for LV mass, MS remained independently associated with higher LA diameter, lower E/A ratio, and lower mean e′ (p ≤0.01 for all). Specifically, subjects with MS had a 1.8 cm/s lower mean e′ compared with controls (p = 0.01). Notably, differences in mean e′ between those with and without MS were more pronounced at younger ages (p for interaction = 0.003). In conclusion, MS was associated with preclinical LV diastolic dysfunction independent of LV mass, as reflected by higher LA diameter, lower E/A ratio, and lower mean e′. This suggests that MS can lead to the development of diastolic dysfunction through mechanisms independent of hypertrophy. Differences in diastolic function were more pronounced at younger ages, highlighting the potential importance of early risk factor modification and preventive strategies in MS. Metabolic syndrome (MS) has been associated with subclinical changes in cardiac structure and function, including diastolic dysfunction and left ventricular (LV) hypertrophy.1de las Fuentes L. Brown A.L. Mathews S.J. Waggoner A.D. Soto P.F. Gropler R.J. Davila-Roman V.G. Metabolic syndrome is associated with abnormal left ventricular diastolic function independent of left ventricular mass.Eur Heart J. 2007; 28: 553-559Crossref PubMed Scopus (135) Google Scholar Previous studies have shown that preclinical LV diastolic dysfunction and LV hypertrophy are strong risk factors for the future development of clinical heart failure and specifically increase the risk of heart failure with preserved ejection fraction.2Bella J.N. Palmieri V. Roman M.J. Liu J.E. Welty T.K. Lee E.T. Fabsitz R.R. Howard B.V. Devereux R.B. Mitral ratio of peak early to late diastolic filling velocity as a predictor of mortality in middle-aged and elderly adults: the Strong Heart Study.Circulation. 2002; 105: 1928-1933Crossref PubMed Scopus (347) Google Scholar, 3Kane G.C. Karon B.L. Mahoney D.W. Redfield M.M. Roger V.L. Burnett Jr., J.C. Jacobsen S.J. Rodeheffer R.J. Progression of left ventricular diastolic dysfunction and risk of heart failure.JAMA. 2011; 306: 856-863Crossref PubMed Scopus (458) Google Scholar The pathways leading to preclinical LV diastolic dysfunction are diverse, and mechanisms of progression to heart failure were poorly understood. In the MS, LV diastolic function and LV hypertrophy appear to worsen in a stepwise fashion with the number of risk factors for MS.1de las Fuentes L. Brown A.L. Mathews S.J. Waggoner A.D. Soto P.F. Gropler R.J. Davila-Roman V.G. Metabolic syndrome is associated with abnormal left ventricular diastolic function independent of left ventricular mass.Eur Heart J. 2007; 28: 553-559Crossref PubMed Scopus (135) Google Scholar, 4Azevedo A. Bettencourt P. Almeida P.B. Santos A.C. Abreu-Lima C. Hense H.W. Barros H. Increasing number of components of the metabolic syndrome and cardiac structural and functional abnormalities—cross-sectional study of the general population.BMC Cardiovasc Disord. 2007; 7: 17Crossref PubMed Scopus (51) Google Scholar These findings may account in part for the augmented cardiovascular morbidity and mortality that is associated with MS.5Ford E.S. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence.Diabetes Care. 2005; 28: 1769-1778Crossref PubMed Scopus (1366) Google Scholar Whether these associations are because of age-related changes, hypertension, or other cardiometabolic effects of MS remains unclear. Further, the true prevalence of preclinical diastolic dysfunction in MS and relation to components of the MS are not well defined. We sought to further characterize cardiac structure and function in subjects with and without MS. Specifically, we hypothesized that MS is associated with preclinical diastolic dysfunction and that this association can occur independent of the hypertrophy. These findings might lend further insight into potential mechanisms by which MS is associated with the eventual development of heart failure.MethodsWe conducted an observational cross-sectional study of consecutive participants with MS who attended outpatient visits at general cardiology, hypertension, obesity, and nutrition clinics at Boston Medical Center. MS was defined as meeting 3 or more of the following criteria: (a) increased waist circumference (≥102 cm in men or ≥88 cm in women), (b) increased fasting triglyceride (≥150 mg/dl), (c) high blood pressure (≥130/85 mm Hg) or antihypertensive therapy, (d) decreased high-density lipoprotein cholesterol (<40 mg/dl in men or <50 mg/dl in women), and (e) impaired fasting glucose (≥100 mg/dl).6Grundy S.M. Cleeman J.I. Daniels S.R. Donato K.A. Eckel R.H. Franklin B.A. Gordon D.J. Krauss R.M. Savage P.J. Smith Jr., S.C. Spertus J.A. Costa F. American Heart ANational Heart L, Blood IDiagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement.Circulation. 2005; 112: 2735-2752Crossref PubMed Scopus (8858) Google Scholar Controls without MS were recruited at Boston Medical Center and were defined as meeting none of the 5 criteria for MS. Participants with existing cardiovascular disease (heart failure, left ventricular ejection fraction [LVEF] <50%, coronary artery disease, or valvular heart disease) were excluded from the study.All participants underwent a comprehensive medical history and physical examination. Heart rate at rest, anthropometrics, blood pressure (obtained after 10 minutes of rest in the sitting position, expressed as the average of 3 consecutive measurements), and fasting blood work were obtained. Hypertension was defined as a systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, and/or current antihypertensive therapy. Severe hypertension was defined as taking 2 or more antihypertensive medications. Diabetes mellitus was defined as a fasting serum glucose level ≥126 mg/dl and/or current medical therapy with an oral hypoglycemic agent and/or insulin. The study was approved by the Boston University Medical Center Institutional Review Board. All participants provided informed consent before study enrollment.Transthoracic echocardiography was performed with 1 to 5 MHz transducer and commercial ultrasound system (Philips iE33, Andover, MA) by an experienced sonographer. Studies were analyzed off-line using a digital echo interface (Philips XCelera, Andover, MA) by a single observer blinded to MS status (NA). Internal dimensions, left ventricle wall thickness, and LVEF (by modified Simpson's rule) were measured according to published recommendations.7Nagueh S.F. Appleton C.P. Gillebert T.C. Marino P.N. Oh J.K. Smiseth O.A. Waggoner A.D. Flachskampf F.A. Pellikka P.A. Evangelista A. Recommendations for the evaluation of left ventricular diastolic function by echocardiography.J Am Soc Echocardiogr. 2009; 22: 107-133Abstract Full Text Full Text PDF PubMed Scopus (2466) Google Scholar, 8Lang R.M. Bierig M. Devereux R.B. Flachskampf F.A. Foster E. Pellikka P.A. Picard M.H. Roman M.J. Seward J. Shanewise J.S. Solomon S.D. Spencer K.T. Sutton M.S. Stewart W.J. Chamber Quantification Writing GroupAmerican Society of Echocardiography's Group, Standards CommitteeEuropean Association of EchocardiographyRecommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.J Am Soc Echocardiogr. 2005; 18: 1440-1463Abstract Full Text Full Text PDF PubMed Scopus (9359) Google ScholarLeft atrial (LA) volume was measured in the apical 2- and 4-chamber views and indexed to body surface area according to published recommendations.7Nagueh S.F. Appleton C.P. Gillebert T.C. Marino P.N. Oh J.K. Smiseth O.A. Waggoner A.D. Flachskampf F.A. Pellikka P.A. Evangelista A. Recommendations for the evaluation of left ventricular diastolic function by echocardiography.J Am Soc Echocardiogr. 2009; 22: 107-133Abstract Full Text Full Text PDF PubMed Scopus (2466) Google Scholar, 8Lang R.M. Bierig M. Devereux R.B. Flachskampf F.A. Foster E. Pellikka P.A. Picard M.H. Roman M.J. Seward J. Shanewise J.S. Solomon S.D. Spencer K.T. Sutton M.S. Stewart W.J. Chamber Quantification Writing GroupAmerican Society of Echocardiography's Group, Standards CommitteeEuropean Association of EchocardiographyRecommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.J Am Soc Echocardiogr. 2005; 18: 1440-1463Abstract Full Text Full Text PDF PubMed Scopus (9359) Google Scholar Relative wall thickness was calculated as the mean of the end-diastolic posterior and septal wall thicknesses, divided by the LV end-diastolic diameter. LV mass was determined by the cubed method and indexed to height to the power of 2.7 to correct for body habitus, and LV hypertrophy was defined as LV mass index >44 g/m2.7 in women and >48 g/m2.7 in men.8Lang R.M. Bierig M. Devereux R.B. Flachskampf F.A. Foster E. Pellikka P.A. Picard M.H. Roman M.J. Seward J. Shanewise J.S. Solomon S.D. Spencer K.T. Sutton M.S. Stewart W.J. Chamber Quantification Writing GroupAmerican Society of Echocardiography's Group, Standards CommitteeEuropean Association of EchocardiographyRecommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.J Am Soc Echocardiogr. 2005; 18: 1440-1463Abstract Full Text Full Text PDF PubMed Scopus (9359) Google Scholar, 9de Simone G. Daniels S.R. Devereux R.B. Meyer R.A. Roman M.J. de Divitiis O. Alderman M.H. Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight.J Am Coll Cardiol. 1992; 20: 1251-1260Abstract Full Text PDF PubMed Scopus (1504) Google Scholar Pulse-wave Doppler-derived transmitral inflow velocities were obtained in the apical 4-chamber view at a sweep speed of 100 mm/s with the sample volume placed at the mitral valve leaflet tips. Measurements included the transmitral early diastolic (E wave) and atrial (A wave) velocities to calculate E/A ratio and E-wave deceleration time.7Nagueh S.F. Appleton C.P. Gillebert T.C. Marino P.N. Oh J.K. Smiseth O.A. Waggoner A.D. Flachskampf F.A. Pellikka P.A. Evangelista A. Recommendations for the evaluation of left ventricular diastolic function by echocardiography.J Am Soc Echocardiogr. 2009; 22: 107-133Abstract Full Text Full Text PDF PubMed Scopus (2466) Google Scholar, 10Levy D. Garrison R.J. Savage D.D. Kannel W.B. Castelli W.P. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study.N Engl J Med. 1990; 322: 1561-1566Crossref PubMed Scopus (4811) Google Scholar Tissue Doppler imaging was used to obtain LV myocardial velocities in the apical 4-chamber view with a sample volume placed at the medial and lateral mitral annulus. Measurements included medial and lateral early diastolic (e′) myocardial velocities, and mean e′ was calculated as the average of medial and lateral e′. All echocardiographic measurements were averaged over 3 consecutive cardiac cycles (when available). Repeated measurements of 10 scans showed an intra-observer coefficient of variation of 0.9% to 4.7% and an intraclass correlation coefficient of 91% to 99% for linear measurements.Baseline clinical characteristics and echocardiographic measurements were summarized for participants with and without MS. Between-group differences in baseline measurements were assessed using 2-sample t tests or Pearson's chi-square tests as appropriate. The association of MS and measurements of cardiac structure and function was assessed using multivariable linear regression. Hierarchical models were constructed, first adjusting for age and gender and then further adjusting for systolic blood pressure, the use of antihypertensive medications, and body mass index (BMI). Lastly, analyses examining measurements of diastolic function that remained associated with MS were further adjusted for LV mass. Because age is known to be a strong determinant of diastolic function,11Munagala V.K. Jacobsen S.J. Mahoney D.W. Rodeheffer R.J. Bailey K.R. Redfield M.M. Association of newer diastolic function parameters with age in healthy subjects: a population-based study.J Am Soc Echocardiogr. 2003; 16: 1049-1056Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar we tested for statistical interaction between age and MS.In exploratory analyses, we examined the association of the total number of MS risk factors and echocardiographic parameters for the subgroup of patients with MS using 1-way analysis of variance. We also examined the association of different components of MS and measurements of cardiac structure and function in participants with MS. Stepwise multivariable regression models were constructed, using forward selection with retention of variables at a p <0.05, forcing age and sex. Models were also repeated using backward elimination. Analyses were performed using STATA version 10.1 (Stata Corp., College Station, Texas) software.ResultsA total of 116 subjects were enrolled in our study, including 90 subjects with MS (mean age 46 years, 78% women) and 26 controls without MS (mean age 43 years, 65% women). Baseline characteristics by group are displayed in Table 1. Overall, subjects with MS had a worse cardiovascular risk factor profile, including higher blood pressure, BMI, and dyslipidemia. Fifty-seven percent of subjects with MS met at least 4 of the established criteria.Table 1Baseline characteristics by metabolic syndrome statusVariableMS (n = 90)Controls (n = 26)Age (years)46 ± 1043 ± 12Women70 (78%)17 (65%)White45 (50%)∗p <0.05 for between group comparisons.21 (81%)Systolic blood pressure (mm Hg)126 (16)∗p <0.05 for between group comparisons.109 (12)Diastolic blood pressure (mm Hg)79 (11)∗p <0.05 for between group comparisons.70 (7)Body-mass index (kg/m2)39 (7)∗p <0.05 for between group comparisons.24 (3)Triglyceride (mg/dl)186 (120)∗p <0.05 for between group comparisons.86 (30)High-density lipoprotein cholesterol (mg/dl)43 (11)∗p <0.05 for between group comparisons.57 (12)Smoker11 (12%)∗p <0.05 for between group comparisons.0Diabetes mellitus35 (39%)∗p <0.05 for between group comparisons.0Anti-hypertensive medication use66 (73%)∗p <0.05 for between group comparisons.0Severe hypertension37 (32%)∗p <0.05 for between group comparisons.0Elevated waist circumference85 (94%)∗p <0.05 for between group comparisons.0Elevated fasting triglyceride57 (63%)∗p <0.05 for between group comparisons.0Low HDL cholesterol70 (78%)∗p <0.05 for between group comparisons.0High blood pressure80 (89%)∗p <0.05 for between group comparisons.0Impaired fasting glucose47 (52%)∗p <0.05 for between group comparisons.0Three MS risk factors39 (43%)∗p <0.05 for between group comparisons.0Four MS risk factors35 (39%)∗p <0.05 for between group comparisons.0Five MS risk factors16 (18%)∗p <0.05 for between group comparisons.0Values are means (standard deviation) unless otherwise noted.∗ p <0.05 for between group comparisons. Open table in a new tab Echocardiographic measurements for control and MS groups are presented in Table 2. Although there were small differences in LV dimensions and LVEF between groups, subjects with MS have greater LV mass, with 28% and 24% meeting criteria for concentric remodeling or concentric hypertrophy, respectively.8Lang R.M. Bierig M. Devereux R.B. Flachskampf F.A. Foster E. Pellikka P.A. Picard M.H. Roman M.J. Seward J. Shanewise J.S. Solomon S.D. Spencer K.T. Sutton M.S. Stewart W.J. Chamber Quantification Writing GroupAmerican Society of Echocardiography's Group, Standards CommitteeEuropean Association of EchocardiographyRecommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.J Am Soc Echocardiogr. 2005; 18: 1440-1463Abstract Full Text Full Text PDF PubMed Scopus (9359) Google Scholar None of the subjects in the control group had concentric hypertrophy, and 2 participants had concentric remodeling. Subjects with MS also had worse measurements of diastolic function, including higher LA diameters, lower E/A ratio, and lower mean e′. Specifically, 34% of subjects with MS had a mean e′ <8 cm/s, whereas only 13% of control subjects had a mean e′ <8 cm/s.Table 2Echocardiographic measurements by metabolic syndrome statusVariableMS (n = 90)Controls (n = 26)p-ValueDimension Left atrial dimension (mm)37 (4)32 (4)<0.001 Left ventricular end diastolic dimension (mm)46 (5)47 (4)0.25 Left ventricular end systolic dimension (mm)30 (4)31 (4)0.46 Posterior wall thickness (mm)9.9 (1.5)7.8 (1.0)<0.001 Interventricular septal thickness (mm)10.0 (1.5)7.7 (1.1)<0.001 Relative wall thickness (cm)0.44 (0.08)0.33 (0.07)<0.001 Left ventricular mass/height2.7 (g/m2.7)39.9 (9.4)28.8 (4.8)<0.001 Left ventricular ejection fraction (%)63 (5)63 (4)0.85Diastolic parameters E (cm/s)80 (16)74 (15)0.14 A (cm/s)72 (17)48 (13)<0.001 E/A ratio1.1 (0.3)1.6 (0.5)<0.001 Deceleration time (ms)203 (44)202 (34)0.95 Mean e′ (cm/s)9.0 (2.0)11.7 (3.0)<0.001 E/mean e′9.2 (2.4)6.6 (1.7)<0.001Values are means (standard deviation). Open table in a new tab In age- and gender-adjusted analyses, MS was associated with echocardiographic features of diastolic dysfunction, including higher LA diameter, higher LV wall thickness, higher LV mass, lower E/A ratio, and lower mean e′ (p <0.001 for all, Table 3). These associations of MS and LA diameter, relative wall thickness, E/A ratio, and mean e′ appeared to be independent of blood pressure, antihypertensive medication use, and BMI (p <0.05 for all; Table 3). After additional adjustment for LV mass, MS remained independently associated with lower E/A ratio (p = 0.002) and lower mean e′ (p = 0.01; Table 3). A total of 32 participants with MS (34%) had a mean e′ <8 cm/s, of whom 15 (47%) had low mean e′ in the absence of LV hypertrophy criteria.Table 3The association of metabolic syndrome with echocardiographic measuresAge- and Gender-AdjustedAge-, Gender-, Blood Pressure- and BMI-AdjustedAge-, Gender-, Blood Pressure-, BMI, and LV Mass-Adjustedβ Estimate (s.e.)p Valueβ Estimate (s.e.)p Valueβ Estimate (s.e.)p ValueLeft atrial dimension5.0 (0.8)<0.0013.5 (1.4)0.013.5 (1.4)0.01Left ventricular end diastolic dimension−0.6 (1.1)0.55Left ventricular end systolic dimension−0.1 (0.9)0.89Posterior wall thickness2.2 (0.3)<0.0010.8 (0.5)0.11Interventricular septal thickness2.5 (0.3)<0.0011.1 (0.5)0.021.2 (0.4)0.001Relative wall thickness0.10 (0.02)<0.0010.07 (0.03)0.010.07 (0.03)0.01Left ventricular mass/height2.711.2 (2.0)<0.001−1.2 (2.8)0.66Left ventricular ejection fraction (%)−0.1 (1.2)0.90E (cm/s)6.4 (3.6)0.08−1.9 (5.6)0.73A (cm/s)21.0 (3.3)<0.00112.1 (5.2)0.0211.9 (5.2)0.02E/A ratio−0.4 (0.1)<0.001−0.4 (0.1)0.002−0.4 (0.1)0.002Deceleration time (ms)−3.3 (10.2)0.75Mean e′ (cm/s)−2.2 (0.4)<0.001−1.7 (0.7)0.015−1.8 (0.7)0.01E/mean e′2.2 (0.5)<0.0010.8 (0.8)0.32β estimate represents the change in echocardiographic measure in the presence versus absence of metabolic syndrome. Open table in a new tab Although LA diameter was significantly higher in MS in multivariable-adjusted models, LA volume when indexed to body surface area was not significantly associated with MS after accounting for blood pressure and BMI (p >0.05).In sensitivity analyses including only white subjects (45 MS, 21 controls), primary results were not materially different. Similarly, results did not change appreciably after adjusting for smoking status or diabetes mellitus status.Among the different echocardiographic measurements that were found to be significantly associated with MS, age was a significant predictor of A, E/A ratio, and mean e′. To further explore whether age is an effect modifier in the associations between MS and diastolic function measurements, we tested for an age interaction term. There was a significant interaction between age and MS as predictors of mean e′ (p = 0.003), suggesting that although MS was associated with lower mean e′ at any age, this difference was most pronounced at younger ages (Figure 1). For example, for a man aged 30 years with a systolic blood pressure of 120 mm Hg and BMI of 30, the predicted mean e′ was 11.0 cm/s in patients with MS and 14.3 cm/s in those without MS. In contrast, at age 50 years for the same clinical criteria, the predicted mean e′ was 9.3 cm/s with MS and 10.3 cm/s without MS.In exploratory analyses, we examined the association of the total number of MS risk factors and echocardiographic parameters within patients with MS. The number of MS risk factors was associated with E/A ratio (p = 0.003) and mean e′ (p = 0.03) but not other echocardiographic parameters. We further examined the association of individual components of the MS and echocardiographic measurements using stepwise selection models. In multivariable analyses, increased waist circumference and lower high-density lipoprotein cholesterol were independently associated with increased LV mass after adjustment for age and sex (p <0.05 for all). Elevated triglycerides were associated with mean e′ after adjustment for age and sex.DiscussionWe found that MS was associated with preclinical LV diastolic dysfunction as reflected by higher LA diameter, lower E/A ratio, and lower mean e′ in a sample of patients without existing cardiovascular disease. Notably, this association was independent of other clinical factors commonly associated with diastolic dysfunction, including age, blood pressure, and LV mass.3Kane G.C. Karon B.L. Mahoney D.W. Redfield M.M. Roger V.L. Burnett Jr., J.C. Jacobsen S.J. Rodeheffer R.J. Progression of left ventricular diastolic dysfunction and risk of heart failure.JAMA. 2011; 306: 856-863Crossref PubMed Scopus (458) Google Scholar, 10Levy D. Garrison R.J. Savage D.D. Kannel W.B. Castelli W.P. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study.N Engl J Med. 1990; 322: 1561-1566Crossref PubMed Scopus (4811) Google Scholar, 11Munagala V.K. Jacobsen S.J. Mahoney D.W. Rodeheffer R.J. Bailey K.R. Redfield M.M. Association of newer diastolic function parameters with age in healthy subjects: a population-based study.J Am Soc Echocardiogr. 2003; 16: 1049-1056Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar These findings suggest that MS can lead to the development of diastolic dysfunction through mechanisms that are independent of hypertrophy and potentially lend further insights into the increased cardiovascular risk observed in MS.5Ford E.S. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence.Diabetes Care. 2005; 28: 1769-1778Crossref PubMed Scopus (1366) Google Scholar, 12Gami A.S. Witt B.J. Howard D.E. Erwin P.J. Gami L.A. Somers V.K. Montori V.M. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies.J Am Coll Cardiol. 2007; 49: 403-414Abstract Full Text Full Text PDF PubMed Scopus (1419) Google Scholar Further, we found that age acts as an effect modifier, such that differences in diastolic function in participants with and without MS were more pronounced at younger ages. This may be because of bigger differences in subclinical cardiovascular disease at younger ages, which attenuate with increasing age and the development of other co-morbidities. The presence of preclinical diastolic dysfunction at younger ages highlights the importance of future studies focused on early risk factor modification and preventive strategies in MS.Our results are consistent with previous studies showing an association of MS and increased LV mass.13Burchfiel C.M. Skelton T.N. Andrew M.E. Garrison R.J. Arnett D.K. Jones D.W. Taylor Jr., H.A. Metabolic syndrome and echocardiographic left ventricular mass in blacks: the Atherosclerosis Risk in Communities (ARIC) Study.Circulation. 2005; 112: 819-827Crossref PubMed Scopus (75) Google Scholar, 14Chinali M. Devereux R.B. Howard B.V. Roman M.J. Bella J.N. Liu J.E. Resnick H.E. Lee E.T. Best L.G. de Simone G. Comparison of cardiac structure and function in American Indians with and without the metabolic syndrome (the Strong Heart Study).Am J Cardiol. 2004; 93: 40-44Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar, 15de Simone G. Devereux R.B. Chinali M. Roman M.J. Lee E.T. Resnick H.E. Howard B.V. Metabolic syndrome and left ventricular hypertrophy in the prediction of cardiovascular events: the Strong Heart Study.Nutr Metab Cardiovasc Dis. 2009; 19: 98-104Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar Although elevated blood pressure is one of the important components of MS, and hypertension is known to lead to increases in LV mass,16Lorell B.H. Carabello B.A. Left ventricular hypertrophy: pathogenesis, detection, and prognosis.Circulation. 2000; 102: 470-479Crossref PubMed Scopus (829) Google Scholar we found that the association of MS and increased LV mass was independent of blood pressure. Further, in exploratory analyses, we show that measurements of obesity and lower high-density lipoprotein cholesterol influence LV mass in patients with MS. These results showing the association of metabolic disease and increased LV mass are consistent with previous studies looking at MS or its risk factors that have linked increases in LV mass with dyslipidemia17Horio T. Miyazato J. Kamide K. Takiuchi S. Kawano Y. Influence of low high-density lipoprotein cholesterol on left ventricular hypertrophy and diastolic function in essential hypertension.Am J Hypertens. 2003; 16: 938-944Crossref PubMed Scopus (74) Google Scholar and obesity.18Guerra F. Mancinelli L. Angelini L. Fortunati M. Rappelli A. Dessi-Fulgheri P. Sarzani R. The association of left ventricular hypertrophy with metabolic syndrome is dependent on body mass index in hypertensive overweight or obese patients.PLoS One. 2011; 6: e16630Crossref PubMed Scopus (43) Google ScholarA number of previous studies have demonstrated subclinical cardiac remodeling in MS1de las Fuentes L. Brown A.L. Mathews S.J. Waggoner A.D. Soto P.F. Gropler R.J. Davila-Roman V.G. Metabolic syndrome is associated with abnormal left ventricular diastolic function independent of left ventricular mass.Eur Heart J. 2007; 28: 553-559Crossref PubMed Scopus (135) Google Scholar, 19Masugata H. Senda S. Goda F. Yoshihara Y. Yoshikawa K. Fujita N. Daikuhara H. Nakamura H. Taoka T. Kohno M. Left ventricular diastolic dysfunction as assessed by echocardiography in metabolic syndrome.Hy" @default.
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• W2054570956 title "Preclinical Left Ventricular Diastolic Dysfunction in Metabolic Syndrome" @default.
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