Assessment of Left Ventricular Function in Patients with Metabolic Syndrome: A Strain Imaging Study

Abstract

Background:

Metabolic syndrome (MS) prevalence remains linked to elevated risk for cardiovascular morbidity and mortality, making it a critical public health issue. Two-dimensional speckle-tracking echocardiography (2D-STE) facilitates early detection of subclinical left ventricular (LV) dysfunction, enabling preventing or postponing cardiovascular disease development.

Objective:

The objective of this study was to assess LV systolic function among MS cases by 2D-STE.

Patients and Methods:

Our case–control study included 80 cases of both genders, aged between 30 and 56 years, divided into two groups: patient group (n = 50): cases Developing MS characteristics and control group (n = 30): healthy volunteers. All subjects underwent conventional echocardiographic examination and assessment of LV systolic function utilizing 2D-STE.

Results:

LV systolic function, assessed by global longitudinal strain (GLS), showed significant impairment in MS cases compared to normal subjects (−12.9 to −20.8 vs. −17 to 23.3, P < .001), with a higher proportion of females exhibiting impaired GLS than males (31 cases, 70.4% vs. 8 cases, 18.8%) and a dose-dependent correlation between an increased number of MS components and LV systolic dysfunction. Furthermore, the prevalence of LV diastolic dysfunction showed an increase within the MS group as opposed to control subjects. There was a clear strong negative correlation between global strain and waist circumference and triglyceride level (P < 0.05).

Conclusions:

There is a correlation between MS and impaired LV systolic and diastolic function among middle-aged adults who do not exhibit any prevalent heart conditions that could be detected by speckle-tracking echocardiography.

INTRODUCTION

Metabolic syndrome (MS) stands as a cardiovascular risk factor, comprising abdominal obesity, hypertension, impaired glucose tolerance, insulin resistance, and elevated triglycerides (TGs), along with reduced high-density lipoprotein cholesterol (HDL) levels. It affects approximately 25% of the adult population and may contribute to heart failure, diabetes, myocardial infarction, as well as stroke.[1]

MS has been linked to both systolic and diastolic dysfunction (DD) as detected utilizing tissue Doppler imaging (TDI); nevertheless, ejection fraction (EF), the predominant parameter for assessing systolic function, exhibits limited sensitivity in evaluating early cardiac contractility dysfunction.[2]

The newly introduced echocardiographic techniques, involving global longitudinal strain (GLS) employing two-dimensional speckle-tracking echocardiography (2D-STE), facilitate the evaluation of subclinical left ventricular (LV) dysfunction through quantitatively analyzing myocardial deformation.[3,4]

PATIENTS AND METHODS

Our team designed a case–control study including 80 cases, with ages falling between 30 and 56 years, both genders. We categorized participants into two groups: the patient group (n = 50), consisting of individuals who meet the MS criteria based on IDF guidelines, and the control group. MS is diagnosed when at least three out of five defined components are present:

1. Specific gender and ethnicity: Waist circumference standards for individuals of European ethnicity were established at ≥94 cm for men while ≥80 cm for females. For Asian populations, except the Japanese, the thresholds were established at 90 cm or more for men while 80 cm or greater for females; conversely, regarding the Japanese, the thresholds were set at 85 cm or greater for men while 90 cm or greater for females

2. Reduced HDL (below 40 mg/dl [1.03 mmol/l] among males while below 50 mg/dl [1.29 mmol/l] among females or lipid-lowering medication)

3. Hypertriglyceridemia (≥150 mg/dl or lipid abnormality treatment).

4. Hypertension (≥130/85 mmHg or hypertension treatment)

5. Hyperglycemia (fasting plasma glucose equal to or more than 100 mg/dl, diagnosed with type 2 diabetes mellitus [T2DM]).

and control group (n = 30): healthy control subjects who did not exhibit any cardiovascular risk factors.

We conducted this research within a timeframe between June 2022 and December 2023 after being approved by the Ethical Committee Menoufia University Hospitals (Approval code:3/2018CARD1), Menoufia, Egypt. Our team gathered signed informed consent from all participants.

Our team excluded cases developing overt ischemic heart disease, those who were previously diagnosed with coronary artery disease, the existence or absence of pathologic Q waves within a minimum of two adjacent leads on resting 12-lead electrocardiogram (ECG), LVEF of below 55%, bundle branch block in ECG, valvular heart disease, congenital heart disease, cardiomyopathies, chronic kidney disease as well as cases who disagreed to take part in the research.

Our team also gathered a comprehensive medical history from all participants, then we carried out clinical examination as well as laboratory testing (total lipid profile, fasting blood suger [FBS], glycated hemoglobin [HbA1C], and liver and renal and hepatic function testing) as well as radiological investigations (electrocardiogram [ECG], conventional echocardiography, TDI, as well as 2D-STE). Measuring body weight was conducted in kilograms while height was in meters. Using these measurements, we calculated body mass index (BMI) following this formula (BMI = weight [kg]/height² [m]). Measuring the waist circumference was conducted at the midpoint between the rib cage’s bottom edge and the iliac crest while the individual was in upright position utilizing a flexible tape. Assessment of systemic blood pressure as well as heart rate was also carried out.

Echocardiography

A conventional echocardiographic investigation, together with TDI and 2D speckle tracking, was carried out employing the Philips HD 11 ultrasound equipment. All participants were assessed at the left lateral decubitus posture in accordance with the guidelines of the European Society of Echocardiography and then were attached to a single-lead ECG.

Conventional Echo involving. Measurements of M-mode Echo. were obtained at the end diastole utilizing the widest LV cavity diameter, while the narrowest LV cavity diameter was at the end-systole. The acquired M-mode assessments, interventricular septum end-diastolic thickness (IVSD), posterior wall end-diastolic thickness (PWD), left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), left atrial dimensions (LA), and aortic root dimensions (AO). Assessing systolic function, measuring LV EF % as well as LV fractional shortening (FS %) was conducted for evaluating LV systolic function. Utilizing 2D echo, our team measured LV end-diastolic volume as well as LV end-systolic volume from the apical two- and four-chamber views employing a modified biplane Simpson’s method. In addition, we calculated EF % as percentage change of LV chamber volumes between diastole as well as systole. Doppler flow measures: our team assessed mitral valve flow employing pulsed wave Doppler, thus measuring early and late diastolic mitral flow along with their ratio (E-velocity, A-velocity, and E/A ratio, respectively). Furthermore, we utilized continuous wave Doppler for assessing flow over tricuspid as well as aortic valves. Color flow Doppler: Our team utilized color Doppler while assessing flow over the cardiac valves. Pulsed-wave Tissue Doppler Imaging (TDI) was used to assess the mitral annulus systolic velocity (S’), early diastolic velocity (e’), and late diastolic velocity (a’) in the apical four-chamber view at both the septal and lateral annulus. We utilized the mean of septal along with lateral e’ for E/e’ ratio calculation.

Two-dimensional speckle-tracking echocardiography

Our team obtained longitudinal strain images from the apical four-chamber, three-chamber, and two-chamber views, recording three consecutive cardiac cycles for each view while ensuring a stable and clear ECG signal during end-expiratory breath hold. The software employs speckle tracking at the endocardial border throughout the cardiac cycle. Peak LS underwent an automatic calculation, producing regional data from six segments together with an average value for each view.

Statistical analysis

Our team conducted statistical analysis utilizing SPSS v26 (IBM Inc., Chicago, IL, USA). Quantitative variables were illustrated as mean and standard deviation (SD), and a comparison was carried out among both the groups employing an unpaired Student’s t-test. Qualitative variables were showcased as frequency and percentage (%), and analysis was conducted employing the Chi-square or Fisher’s exact test when appropriate. Assessing the associations among different variables was carried out employing the Pearson moment correlation equation. A two-tailed P value of below 0.05 was deemed statistically significant.

RESULTS

Increased age, female sex, weight, BMI, waist circumference, DM, and HTN showed significantly greater values among the MS group as opposed to the control group (P < 0.001) [Table 1].

Table 1.

Demographic, clinical data, and risk factors of the groups

	MS group (n=50)	Control group B (n=30)	P
Demographic and clinical data
Age (years)	45.98±5.74	39.4±7.89	<0.001*
Sex
Male	19 (38.0)	16 (53.33)	<0.001*
Female	31 (62.0)	14 (46.67)
Weight (kg)	98.98±15.61	74.33±16.82	<0.001*
Height (m)	1.71±0.11	1.72±0.13	0.900
BMI (kg/m2)	33.93±6	24.93±3.24	<0.001*
Waist circumference (cm)	110.52±9.66	85.73±5.87	<0.001*
Clinical and risk factors
Smoking	18 (36.0)	6 (20.0)	0.131
DM	28 (56.0)	0	<0.001*
HTN	28 (56.0)	4 (13.33)	<0.001*

*Significant P<0.05. Data are presented as mean±SD or frequency (%). BMI=Body mass index, DM=Diabetes mellitus, HTN=Hypertension, MS=Metabolic syndrome, SD=Standard deviation

ALT, AST and TG, HbA1C, FBG, IVSD, LVIDs, LVPWD, LA dimension, aortic root diameter, LV mass, MV Am, E/E’, LA volume index, and TR jet velocity showed a significant increase within Group A as opposed to Group B (P < 0.001). HDL, MV Em as well as MVE. A showed a significant reduction within Group A as opposed to Group B (P < 0.001). Serum creatinine, LVIDD, EF as well as FS showed an insignificant variance among the two groups [Table 2].

Table 2.

Laboratory and radiological investigations of the groups

	MS group (n=50)	Control group (n=30)	P
HbA1C (%)	6.9±1.38	5.05±0.2	<0.001*
FBG (mg/dL)	128.96±32.89	89.4±11.95	<0.001*
ALT (U/L)	28.58±10.33	19±7.21	<0.001*
AST (U/L)	31.68±9.63	19.93±3.49	<0.001*
TG (mg/dL)	205.44±38.42	113.07±15.75	<0.001*
HDL (mg/dL)	44.1±8.99	57±8.56	<0.001*
Serum creatinine (mg/dL)	0.88±0.09	0.85±0.13	0.300
IVSD (cm)	1.09±0.13	0.91±0.22	<0.001*
LVIDd (cm)	4.81±0.4	4.42±1.43	0.069
LVIDs (cm)	3.15±0.35	2.83±0.43	<0.001*
LVPWD (cm)	1.11±0.15	0.94±0.14	<0.001*
EF (%)	65.38±3.92	66.4±3.21	0.233
FS (%)	34.46±2.98	35.2±1.71	0.218
Aortic diameter (cm)	3.54±0.38	3.15±0.39	<0.001*
LA diameter (cm)	3.91±0.23	3.51±0.47	<0.001*
LV mass (g)	197.36±40.41	140.9±66.56	<0.001*
MV Em (cm)	63.9±11.09	81.93±12.05	<0.001*
MV Am (cm)	65.9±17.14	57.07±9.34	0.011*
MVE.A (m/s)	1±0.31	1.35±0.22	<0.001*
E/e’	9.54±1.77	6.06±0.74	<0.001*
LA volume index (mL/m2)	37±3.73	27.82±2.46	<0.001*
TR jet velocity (m/s)	3.19±3.59	2.16±0.24	0.044*

*Significant P<0.05. Data are presented as mean±SD. HbA1C=Glycated hemoglobin, FBG=Fasting blood glucose, LA=Left atrium, LV=Left ventricular, ALT=Alanine transaminase, AST=Aspartate aminotransferase, TG=Triglyceride, HDL=High-density lipoprotein, IVSD=Interventricular septum of diastole, LVIDD=LV internal diameter at end-diastole, LVIDs=LV internal diameter at end-systole, LVPWD=LV posterior wall diastole, EF=Ejection fraction, FS=Fractional shortening, MS=Metabolic syndrome, TR=Tricuspid regurgitation, E: Peak Early diastolic transmital flow, A: Peak late diastolic transmital flow, e’: Early diastolic mitral annular velocity

The apical 2-chamber (A2C), apical 4-chamber (A4C), and apical long-axis (LAX) views, and global strain showed a significant reduction within MS group as opposed to controls (P < 0.001). The patients’ number with impaired systolic function showed a significant increase within the MS group as opposed to controls (P < 0.001) [Table 3].

Table 3.

Global longitudinal left ventricular strain and impaired systolic function of the groups

	MS group (n=50)	Control group (n=30)	P
Longitudinal strain apical 2	17.73±3.17	21.91±1.64	<0.001*
Longitudinal strain apical 4	17.97±2.68	21.97±1.66	<0.001*
Apical long axis	16.01±2.33	21.26±1.69	<0.001*
Global strain	16.68±1.77	20.79±1.96	<0.001*
Impaired systolic function	39 (78.0)	5 (16.67)	<0.001*

*Significant P<0.05. Data are presented as mean±SD or frequency (%). MS=Metabolic syndrome

As regards the patient group, a positive association was documented among global strain and HDL, MVEM, MVEA, LS apical 2, LS apical 4, and apical long axis (P < 0.001). Furthermore, a negative association was documented between global strain and age, weight, BMI, waist circumference, smoking, DM, HTN, number of risk factors, HbA1c, FBG, ALT, AST, TG, LVIDs, aortic diameter, LA diameter, LV mass, E/E’, and LA volume index (P < 0.05). Waist circumference and TG were the factors having a strong negative correlation with global strain [Figure 1].

Figure 1.

Correlation between global longitudinal strain and all studied parameters in metabolic syndrome group

The multivariate regression analysis identifies waist circumference (P = 0.002, 95% CI: 1.167 to 1.989), IVSD (P = 0.001, 95% CI: 36.975 to 6440153.594), LV mass (P = 0.014, 95% CI: 1.004 to 1.040), LVIDs (P = 0.014, 95% CI: 1.575 to 58.771), and longitudinal strain in apical 2-chamber (P = 0.003, 95% CI: 0.344 to 0.813) and apical 4-chamber (P = 0.001, 95% CI: 0.377 to 0.780) as significant predictors of metabolic syndrome (P ≤ 0.05) [Table 4].

Table 4.

Multivariate regression of variables versus metabolic syndrome

	Multivariate
	OR	95% CI	P
Age (years)	1.1297	0.839–1.520	0.420
Weight (kg)	1.0600	0.918–1.222	0.424
BMI (kg/m2)	1.0908	0.690–1.722	0.709
Waist circumference (cm)	1.5241	1.167–1.989	0.002*
HbA1C (%)	1318.4515	0.042–40,505,241.984	0.173
ALT (U/L)	1.1525	0.712–1.865	0.563
AST (U/L)	6.4105	0.636–64.542	0.114
Aortic diameter (cm)	1.4827	0.112–19.466	0.764
LA volume index (mL/m2)	0.2827	0.145–0.548	<0.001*
LA diameter (cm)	17.7066	0.803–390.415	0.068
IVSD (cm)	15,431.8106	36.975–6,440,153.594	0.001*
LV mass (g)	1.0221	1.004–1.040	0.014*
LVIDs (cm)	9.6226	1.575–58.771	0.014*
LVPWD (cm)	0.0156	0.000–27.656	0.275
Longitudinal strain apical 2	0.5291	0.344–0.813	0.003*
Longitudinal strain apical 4	0.5425	0.3770–0.780	0.001*
MV Am (cm)	0.8662	0.6195–1.211	0.400
MVE.A (m/s)	56,210.1588	4.4418–711.310	0.673
MV Em (cm)	0.5902	0.170–2.040	0.404
E/e’	6458.8828	0.0009–45.8	0.275

*Significant as P≤0.05. CI=Confidence interval, OR=Odd ratio, BMI=Body mass index, HbA1C=Glycated hemoglobin, ALT=Alanine transaminase, AST=Aspartate aminotransferase, LA=Left atrium, LV=Left ventricular, IVSD=Interventricular septum of diastole, LVIDD=LV internal diameter at end-diastole, LVIDs=LV internal diameter at end-systole, E: Peak Early diastolic transmital flow, A: Peak late diastolic transmital flow, e’: Early diastolic mitral annular velocity

DISCUSSION

Various studies have indicated that the prevalence of MS differs among ethnic groups. For example, certain populations such as Hispanic/Latino and African American individuals have been found to have higher rates of metabolic syndrome compared to Caucasian populations.[5,6] Regions with lower socioeconomic status may experience higher rates of obesity and MS due to limited access to healthy foods, safe places for physical activity, and healthcare services.[7]

MS constitutes a group of metabolic anomalies, involving central obesity, dyslipidemia, hypertension, as well as insulin resistance, which is linked to greater cardiovascular disease risks and other metabolic conditions.[8]

A possible cardiovascular consequence of metabolic syndrome is LV dysfunction, which may present as impaired LV GLS. GLS serves as a sensitive indicator of subclinical LV dysfunction, measured utilizing STE.[9]

Our research was aimed at investigating the correlation between MS and its components with impaired LV GLS employing various GLS cutoffs within middle-aged adults who did not exhibit any prevalent cardiovascular conditions.

As regards our research, advancing age, female gender, weight, BMI, as well as waist circumference exhibited a significant rise within the MS group as opposed to controls.

Our research also indicated that MS cases were older, with ages ranging from 30 to 56 years, compared to 25 to 50 years in the control group. Supporting our findings, Ford et al.[10] addressed that MS cases were older as opposed to the control group. Conversely, Abagre et al.[11] did not address any association between MS and advancing age.

The disparity in the prevalence of MS among females can be attributed to a complex interplay of hormonal, genetic, and lifestyle factors.[12] Estrogen has protective effects on cardiovascular health and metabolism. It helps regulate fat distribution and improves insulin sensitivity. After menopause, estrogen levels decline, leading to increased visceral fat accumulation and insulin resistance, which can elevate the risk of developing MS. The perimenopausal phase is often accompanied by significant hormonal fluctuations and increased insulin resistance, which can contribute to weight gain, particularly in the abdominal region. This can subsequently raise the risk of MS.[13]

As regards our research, the gender distribution among 50 MS cases was 19 males and 31 female females. This supports Abagre et al.[11] addressed that women exhibited greater chances for being diagnosed with MS in comparison to males. In contrast to our findings, Hathur et al.[14] addressed greater odds of MS among males in comparison to females.

The obesity prevalence was evident at higher rates within the study sample, accounting for 62% of women while 48% of males, thus explaining the greater rate (55%) of MS within our research. Aligned with our research, Ford et al.[10] addressed that MS cases exhibited higher levels of BMI as opposed to those without MS.

In our research, a significant rise was documented among the MS group as opposed to controls as regards diabetes, which supports Abagre et al.[11] indicated that MS was prevalent (68.6%) among T2DM cases attending routine clinics in suburban hospitals in the middle-belt region of Ghana.

In our research, a significant rise was documented within the MS group as opposed to controls as regards HTN. Supporting our findings, Abd Elaziz et al.[15] addressed that 76.6% of HTN cases developed MetS.

As regards our research, significant variances were documented among the MS and control groups as regards TG, HbA1C, fasting blood sugar, ALT, and AST, indicating significantly greater values within the MS group. HDL showed a significant reduction within the MS group. Aligned with our findings, Abagre et al.[11] addressed lower HDL-cholesterol among the three principal MS components.

In the current research, when assessing LV diastolic function utilizing conventional as well as Doppler echo, we observed a correlation between MS and LVDD, evidenced by elevated LA volume index mL/m², reduced E/A ratio, TR jet velocity >2.8 m/sec, and lower e\ septal and lateral wave along with elevated average E/e\ ratio as opposed to controls. Such findings support Nir et al.[16] addressed an association between MS and increased LA volume index d, elevated LV mass, reduced E/A ratio, as well as diminished mean e\.

When assessing LV systolic function utilizing conventional echocardiography, it was shown that conventional echocardiography did not identify early LV systolic function abnormalities since no significant variance was documented among the MS group as well as controls as regards LV EF and FS. Whereas 2D STE demonstrated greater sensitivity than conventional echocardiography in detecting reduced intrinsic myocardial contractility, indicated by global longitudinal strain impairment, the number of patients with impaired systolic function was significantly higher in the MS group.

Cases who exhibited reduced global longitudinal peak systolic strain were 39 patients representing about (78%) of Group 1, while there were 5 individuals representing about 16% of Group B – control group. Such findings supported Wang et al.[17] addressed no significant variances among both the groups regarding LV EF as well as FS. Furthermore, in agreement with us Almeida et al.[18] reported that using STE analysis, longitudinal myocardial functions were reduced, as indicated by lower GLS in participants developing MS as opposed to others without MS.

In this research, when assessing LV systolic and diastolic function utilizing conventional and 2D-STE, there were five individuals in Group II or the control group with DD grade I and decreased GLS despite being metabolically healthy individuals which means that there could be a significant association between obesity and increased risks for subclinical LV systolic dysfunction. Supporting our research, Almeida et al.[18] found that when all five components of MS and all possible interactions between terms were analyzed on MLR analysis, only increased WC remained significantly associated with decreased GLS on STE. In agreement with us also Burroughs Peña et al.[19] demonstrated that high waist circumference and elevated TGs were linked to decreased LV systolic function as assessed utilizing LS.

The research limitations involved modest sample size. We also included cases with varying onset, and severity, as well as treatment strategies of MS components. Other clinical risk factors related to LV dysfunction, involving indicators of inflammation, were excluded from our investigation. All participants exhibited no anginal indications or symptoms and showed normal results on both the ECG as well as 2D echocardiogram; nevertheless, we could not entirely rule out asymptomatic coronary artery disease. We employed a standardized cutoff value without including age as a criterion for LV dysfunction diagnosis.

CONCLUSIONS

There is a correlation between MS and impaired LV systolic and DD among middle-aged adults who did not show any prevalent heart conditions. This could be attributed to underlying metabolic and cardiovascular abnormalities. The results emphasize the need of early identification as well as intervention for MS, thus delaying or preventing the emergence of cardiovascular disease and its associated negative consequences among populations at risk.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.