State of Art Paper
 

3D Echocardiography:
“The Most Powerful Predictor Of Masked CVD In Metabolic Syndrome” 


H. K. Chopra, K. K. Aggarwal, Krishna C. K, Ravinder S.Sambi, S.K.Parashar, Rakesh Gupta,
R.R.Kasliwal, Sanjay Mittal, Manish Bansal, A.K.Gaur, V.Anand, A.K. Bali V. Langer,
A.Vermani, Jagadeesh.K.N Sundeep Mishra, Navin C Nanda, .

Department of Cardiology,
Moolchand Medcity, Metro Heart Institute, JROP Health Care, Apollo Hospital,
New Delhi; University of Alabama at Birmingham, USA.
Abstract

Aims & Objective: To evaluate the impact of the Metabolic Syndrome (MS) on various echo variables by 3D echocardiography.
Materials and methods: 100 patients of MS from indoor and outdoor patient departments were subjected to Echocardiographic and Carotid Doppler evaluation. They were divided into three groups: Group A, Group B and Group C on the basis of age < 40 yrs, 40-60 yrs and > 60 yrs respectively. The echo variables included left ventricular myocardial performance index (LVMPI), left ventricular mass index (LVMi), left ventricular diastolic dysfunction (LVDD), systolic function (LVEF), left atrial volume index (LAVi) and composite common carotid intima media thickness (CCIMT).
Results: The mean LVMPI was abnormal in all the groups and showed an increasing trend with prolonged LVMPI (> 0.4) in 74% of the total population. Prolonged LVMPI in Group A, Group B and Group C was 12.1%, 52.7 % and 35.1% respectively. There was also a strong correlation between LVMPI & LVDD (p-value < 0.0001).  The mean LVEF was normal in all the groups with only 9 % had systolic dysfunction (LVEF < 50%). 68% had abnormal diastolic function, of which 53 % had grade I LVDD, 12 % had grade II LVDD and 3 % had grade III diastolic dysfunction. None of our patients had grade IV diastolic dysfunction. The mean LAVi was normal in all the groups, but LAVi increased with worsening LVDD. The mean LVMI indexed to Body Surface Area (BSA) was normal in all the groups, but showed a statistically significant increasing trend from Group A to Group C (p-value < 0.05).  Statistically significant higher LVMI values were observed for males as compared to females (p value < 0.0001). On analysis of patients having left ventricular hypertrophy (LVH), 76% had concentric remodelling; only 11 % had concentric hypertrophy, but none had eccentric hypertrophy. Most of our patients in Group B & Group C had higher mean Composite CCIMT (0.73 ± 0.33 & 0.84 ± 0.42 respectively) which was statistically very significant (p-value <0.001)
Conclusion: Metabolic Syndrome is associated with masked CVD as evident by 3D Echo in our series of patients. LVMPI was an early indicator and most robust marker of early LVDD. Impaired relaxation was highly prevalent; while on the contrary LAVI was less robust predictor of LVDD in our series of patients. Concentric left ventricular remodeling was the most common pattern of LVH. Most of our series of patients had increased Composite CCIMT. Thus 3D Echocardiography has a great potential and is very useful for early detection and timely therapeutic interventions in patients with subclinical CVD in MS.
(Keywords: Metabolic Syndrome, 3D echocardiography, left ventricular myocardial performance index, left ventricular mass index, left ventricular hypertrophy, left ventricular diastolic dysfunction, systolic function, left atrial volume index  and composite common carotid intima media thickness.)

INTRODUCTION

The Metabolic syndrome (MS) is a condition that is associated with the clustering of risk factors including high blood pressure, abdominal obesity, glucose intolerance and dyslipidemias, that increases cardiovascular morbidity and

mortality 1-4.  Given the clustering of these risk factors that characterizes MS, it is likely that individuals with MS have a high burden of subclinical disease, which would contribute to the increased risk of overt cardiovascular disease (CVD) associated with MS. Several studies 5-15 have documented the increased

Correspondence: Dr. H.K. Chopra Senior Consultant, department of Cardiology, Moolchand Medcity, New Delhi - 110024, India.
Email:
[email protected]

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prevalence of subclinical CVD in MS, but the syndrome or its components are also associated with pathological changes in cardiac structure and function.
By the widespread application of echocardiography and carotid doppler in clinical practice, clinical research, and epidemiology, opportunities to understand pathological alterations in cardiac structure and function in MS have been greatly enhanced. Echocardiography has become the primary imaging tool in the diagnosis and assessment of cardiac structure and function, as it is noninvasive, portable, reproducible, safe with high accuracy and efficacy in providing detailed anatomic, hemodynamic and physiologic information about the cardiovascular system. Three dimensional (3D) echocardiography offers the ability to improve and expand the diagnostic capabilities of cardiac ultrasound. Hence, echocardiography can be used successfully to provide mechanistic insights on diagnostic, therapeutic and prognostic outcomes and in some cases to measure functional and structural changes that are considered to be of therapeutic importance.
The MS is also a strong risk factor for premature increase in IMT leading to carotid atherosclerosis. From several epidemiological studies it has became clear that the measurement of carotid intima media thickness (IMT) can be applied as a marker for generalized atherosclerosis and as an indicator of cardiovascular risk 16-22. Therefore carotid artery imaging has emerged as a superior, noninvasive adjunct to a standard CVD evaluation and enhances aggressive preventive strategies in MS. However, the long term CVD morbidity and mortality relationship to MS, evaluated by echocardiography including carotid artery imaging may help in predicting premature CVD. Our Study evaluated various echo variables in a hospital based population, to detect presence of occult CVD, which contributes to the increased risk of overt CVD associated with MS.
The main objective of this study was to evaluate echocardiographic and carotid colour Doppler variables in patients with MS. We studied the prevalence of various echo variables and composite common carotid intima media thickness (CCIMT) in all the patients with MS and also compared and correlated them in different age groups.


MATERIALS AND METHODS
Our study population consisted of 100 adult patients above the age of 20 years attending Medicine Outdoor Patient Department (OPD) or admitted in medical wards - Indoor Patient Department (IPD) were divided into three groups: Group A, Group B and Group C on the basis of age < 40 yrs, 40-60 yrs and > 60 yrs respectively. On the basis of history, physical examination and biochemical parameters, MetS was

 

was diagnosed according to the modified National Cholesterol Eradication Program (NCEP) Adult Treatment Panel (ATP) III 23 guidelines in individuals meeting three or more of the following criteria: (a) Increased waist circumference >90 cm in males and >80 cm in females. (b) Hypertriglyceridemia ≥150 mg/dl, (c) Decreased HDL cholesterol: < 40 mg /dl in men and < 50 mg/dl in women, (d) High blood pressure ≥130/85 mmHg and (e) high fasting glucose (impaired glucose tolerance) > 110 mg/dl.
Patients with documented endocrinal disorders such as hypothyroidism, cushing syndrome, acromegaly, pheochromocytoma, or other concomitant cardiac disorders such as valvular heart disease, congenital heart disease, acute congestive heart failure, or cerebrovascular disease, hepatic failure and respiratory failure or acute infection or a history of recent infection during last three weeks and patients with poor echo window were excluded from the study.
All the patients diagnosed as MS were then subjected to Echocardiographic and Carotid Doppler evaluation. The various echo variables included left ventricular myocardial performance index (LVMPI), left ventricular mass index (LVMi), left ventricular diastolic dysfunction (LVDD), systolic function (LVEF), left atrial volume index (LAVi) and composite common carotid intima media thickness (CCIMT).

Statistical Analysis
The data were analyzed using software computer statistical package ‘SPSS 10’. For each variable, the average values and standard deviation were estimated for both patient and control groups. Using multivariate analysis of ‘SPSS 10’, correlations between each variable was defined.  Methods for Statistical Analysis Mean and standard deviation (SD) of the numerical variables with unpaired Student t-test and Chi-square test were used for group comparisons. The Pearson correlation was used for correlation analysis. A probability value of < 0.05 was considered as significant.

 3D ECHOCARDIOGRAPHY

All patients underwent 3 dimensional (3D) echocardiogram performed on Philips iE33, in left lateral decubitus position using 5 to 10 MHz transducer, by a consultant cardiologist experienced in echocardiography.

Assessment of Left Ventricular Myocardial Performance (LVMPI)

LVMPI was calculated as summation of iso-volumetric contraction time (IVCT) and iso-volumetric relaxation time (IVRT) divided by ejection time (ET). The IVCT, IVRT & ET were calculated at the mitral annulus. LVMPI = (ICT+IRT)/ET, was obtained by subtracting ET from the interval between cessation and onset of the mitral inflow velocity
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to give the sum of ICT and IRT. The normal value for LVMPI in the adult population is between 0.34 and 0.40, with some age dependency .

Figure 1: Measurement of myocardial performance index (MPI) using pulsed-Doppler echocardiography with sample volume placed in the left ventricular outflow tract. ‘a’ is the time interval between two consecutive mitral inflow signals and ‘b’ is the ejection time. MPI is calculated as (a-b)/b. In the above example, MPI is 0.49.

 

Assessment of Left Ventricular Hypertrophy

LVH was calculated by determining Left ventricular mass (LVM), Body surface area (BSA), Left ventricular mass index (LVMI) and Relative wall thickness (RWT). Left Ventricular Mass (LVM) was estimated by 3D data sets using Simpson’s method27. A 3D system was developed that automatically integrated 2D echocardiographic images and their positions in real time and calculated left ventricular mass directly from traced endocardial contours without geometric assumptions. The components of LV mass including LV internal dimension (LVID), interventricular septal thickness (IVST), and posterior wall thickness (PWT) were all also measured at end-diastole (d). LV mass estimates were
 
Figure 2: Estimation of left ventricular mass using three-dimensional echocardiography.
 

divided by BSA to create an LV mass index. BSA was calculated using the formula of Dubois and Dubois, (BSA = 0.007184 x W0.425 x H0.725 - Where W is weight in Kg and H is height in cm). LVH was defined in absolute terms as LVMI more than 131 g/m2 in men and more than 100 g/m2 in women28. LVM was also indexed to BMI and height. RWT was assessed to characterize LVH into concentric remodeling, concentric and eccentric hypertrophy28,29. RWT of the LV was expressed as the ratio of twice the posterior wall thickness to the end-diastolic cavity dimension30 i.e. [(2 x PWd ) / LVIDd]. Concentric remodeling was defined as RWT ≥ 0.45 in the absence of LVH. Concentric hypertrophy was defined as RWT ≥ 0.45 in the presence of LVH. Eccentric hypertrophy was defined as RWT < 0.45 in the presence of LVH.

Assessment of systolic function

Left ventricular ejection fraction (LVEF) was taken as the measure of Left Ventricular Systolic function. LVEF was calculated from the 3D data sets by use of Simpson's method31 as mentioned above. A 3D system was developed that automatically integrated 2D echocardiographic images and their positions in real time and calculated left ventricular ejection fraction directly from traced endocardial contours without geometric assumptions. The mean EF in normal population is taken as 59.2 ± 6%32. Systolic dysfunction was defined as EF < 50%.

 

Figure 3: Estimation of left ventricular ejection fraction using three-dimensional chocardiography.

 

Assessment of Diastolic Function

Diastolic function is determined by pulsed-wave Doppler examination of mitral (before and with Valsalva maneuver) and pulmonary venous inflow as well as Doppler tissue imaging of the mitral annulus.

Pulsed-wave Doppler (PWD) derived transmitral inflow velocities were obtained in the apical 4-chamber view with the sample volume placed at the mitral valve leaflet tips33. Measurements
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included the transmitral early diastolic (E-wave) and atrial (A-wave) velocities to calculate E/A ratio, mitral ‘E’ wave deceleration time (MEDT), and the isovolumic relaxation time (IVRT)33. In pulmonary veins (PV) Doppler recordings34 three distinct velocity components were measured: a systolic velocity (PVs), a diastolic velocity (PVd) and atrial flow reversal (PVa) along with the duration of pulmonary vein atrial flow reversal (a-dur). Tissue Doppler imaging (TDI) was used to obtain LV myocardial velocities with a sample volume placed at the mitral annulus35, i.e. to assess early diastolic peak velocity within the septal mitral annulus (e’) to calculate E/E’ ratio.

The grading for diastolic dysfunction was performed using the Galderisi Cardiovascular Ultrasound2005 recommendations36 The mitral inflow early filling velocity
 
 

Figure 4: Estimation of left ventricular filling pressure from mitral inflow and mitral annular tissue velocities. 4a- Mitral inflow early diastolic velocity (E) measured using pulsed-Doppler imaging with sample volume placed at the mitral leaflet tips; 4b- Early diastolic mitral annular tissue velocity (E’) measured at medial annulus using pulsed-Doppler tissue velocity imaging. The ratio of E/E’ in this example is 10.3 which is in the normal range.

(E) to atrial filling velocity (A) ratio was used for initial categorization. If the E/A was <1, grade I DD (impaired relaxation) was present. If the E/A ratio was in the normal range (1-2) and the deceleration time was >150 ms, then the other Doppler indexes were used to determine if filling was normal (normal diastolic function) or "pseudonormal" (grade II DD). If there were two other Doppler indexes suggestive of elevated filling pressures (change in E/A with Valsalva of > 0.50; pulmonary venous systolic [S] velocity less than diastolic [D] velocity; pulmonary venous atrial reversal duration greater than mitral A duration > 35 ms; or ratio of E to the velocity of early mitral annular ascent [E'] of >10), then grade II DD was considered to be present. If the E/A ratio was >2 and the deceleration time was <150 ms, and at least one other Doppler index suggestive of elevated filling pressures was present, the subject was considered to have restrictive pattern grade III DD (if the change in E/A with Valsalva was > 0.50) or grade IV DD (if the change in E/A with Valsalva was < 0.50). These groups (grades III and IV) were combined for the purposes of analysis

Assessment of Left Atrial Volume Index

End-systolic left atrial volumes were measured using real-time 3-dimensional echocardiography images (LAV-3D). Reference ranges for ratio of LAV to body surface area with LAVi >95th percentile was used to define LA enlargement (≥ 30 ml/m2 for women and ≥ 33 ml/m2 for men)37

Figure 5: Estimation of left atrial volume using three-dimensional echocardiography.

CAROTID DOPPLER

Carotid atherosclerosis assessment

Common carotid arteries were examined on both sides, in supine position, with the head turned 45 degrees away from the side being scanned on Philips iE33 machine using 10MHz high resolution linear array transducer and the distance
 
3D Echo as Predictor of masked CVD in MS
 

Figure 6: Measurement of carotid intima-media thickness (CIMT). 6a- Carotid bifurcation with color Doppler; 6b- CIMT measurement using automated edge-detection software with ECG gating. Measurement is performed at the far wall of the distal common carotid artery.

 

between two echogenic lines (the inner line representing the lumen intima interface and the outer line representing the media-adventitia interface) was taken as the intima-media thickness (IMT) in millimetres (mm). Composite CCIMT was calculated as a mean of IMT in the common carotid artery on the right and left sides. An IMT of more than 0.7 mm was considered to represent early changes of atherosclerosis (38).

RESULTS & OBSERVATIONS

The clinical characteristics of the individuals in the three groups are shown in Table.1. There was equal distribution of sexes between the three groups (p-value 0.228).

Table 1: Baseline Characteristics total study population in the three groups
 
 
Variable

 

Group A (n= 13)

 

Group B (n= 57)

 

Group C (n= 30)

Age (yrs)

33.8 ± 5.53

51.98 ± 5.59

71.2 ± 7.3

Male gender

46.2%

61.4%

43.3%

Female gender

53.8%

38.6%

56.7%

Height (cm)

163.08 ± 11.74

163.61 ± 8.01

159.6 ± 9.8

Weight (kg)

89.69 ± 17.04

73.53 ± 13.85

66.5 ±11.8

Body Surface Area (kg/cm2)

1.94 ± 0.21

1.79 ± 0.17

1.69 ± 0.17

Hypertension

15.2%

45.6%

66.6%

Diabetes Mellitus

38.4%

31.6%

36.6%

Abdominal  waist (cm)

106.84 ± 14.02

98.36 ± 9.46

95.04 ± 15.2

Systolic blood pressure (mmHg)

126.92 ± 25.62

146.56 ± 22.82

145.20 ± 24.39

Diastolic blood pressure (mmHg)

80.77 ± 15.53

90.89 ± 12.24

85.3 ± 11.6

HDL cholesterol (mg/dl)

31.32 ± 11.60

31.91 ± 17.07

33.6 ± 13.6

Triglycerides (mg/dl)

181.31 ± 58.66

160.58 ± 69.81

143.4 ± 76.2

Fasting Blood Sugar (mg/dl)

132.77 ± 53.68

131.28 ± 46.73

136.9 ± 48.1

 

Echocardiographic assessment

Left Ventricular Myocardial Performance Index (LVMPI)

The mean LVMPI was abnormal in all the groups and showed an increasing trend with the lowest value in Group A (0.46 ± 0.18), followed by the Group B (0.49 ± 0.18), and highest for the Group C (0.53 ± 0.19) (Fig. 7a). Of the total population 74% had abnormal LVMPI > 0.4, out of which 12.1% in Group A, 52.7 % in Group B, 35.1% in Group C (Fig. 7b). We graded our patients according to prolongation of LVMPI (Chopra’s grading of LVMPI prolongation in MS) – Grade 1 (0.4 – 0.6), Grade 2 (0.61 – 0.8), Grade 3 (> 0.8), (Table.2). We found that most of our patients with prolonged LVMPI had impaired LV diastolic function but normal LV systolic function. There was a strong correlation between LVMPI & LVDD (p-value < 0.0001). It was also found that patients with left ventricular diastolic dysfunction (LVDD) of grade II and above had LVMPI > 0.62. Of the 54 males, 74% had increased LVMPI > 0.4, with a mean LVMPI of 0.49 ± 0.16. Of the 46 females, 73.9% had increased LVMPI > 0.4, with a mean LVMPI of 0.51 ± 0.20.

Fig.7a Mean LVMPI in the three groups of patients with MS

 

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Fig.7b Prevalence of prolonged LVMPI in the three groups of patients with MS

 

Table 2: Chopra’s grading of LVMPI prolongation in MS

Chopra’s grading of
prolonged LVMPI

LVMPI

% of patients with
prolonged LVMPI

Grade I

0.41 – 0.60

75%

Grade II

0.61 – 0.80

16.6%

Grade III

>0.81

8.4%

Left Ventricular function (LVEF and LVDD)

The mean LV ejection fraction was within normal range in all the groups; 59.1 ± 4.0 in Group A, 59.5 ± 6.8 in Group B, and 58.2 ± 8.4 in Group C. Of the total population 9 % had LV systolic dysfunction of which 8.8% in Group B, 13.3% in Group C.
Of the total population 68% had impaired diastolic dysfunction, out of which 53 % had grade I LVDD, 12 % patients had grade II LVDD and 3 % had grade III diastolic dysfunction which was statistically significant (p-value < 0.05). None of our patients had grade IV diastolic dysfunction. While in Group A, 38.5% had grade I LVDD and 30.8% patients had grade II LVDD. None had grade III diastolic dysfunction. When compared with Group C, it was statistically significant (p value < 0.05). Whereas in Group B, 42.1% had grade I LVDD, 12.3% patient had grade II LVDD and 1.8% had grade III LVDD. Whereas in Group C, 76.7% had grade I LVDD, 3.3% patient had grade II LVDD and 6.7% had grade III LVDD, (Fig.8a). The mean E/A ratio showed a decreasing trend with the highest value for the Group A and lowest for the Group C while an increasing trend was seen with E/E’ ratio with lowest value in Group A and highest value in Group C, (Fig.8b).
Of the 54 males 35.2% of them had normal LVDD, 48.1% had grade I LVDD and 14.8 % had grade II LVDD and 1.9% had grade III diastolic dysfunction. Of the 46 females 13 28.3 % of them had normal LVDD, 58.7 % had grade I LVDD and 8.7 % had grade II LVDD and 4.3 % had grade III diastolic dysfunction.

Fig.8a: Prevalence of grades of LVDD in the three groups of patients with MS

 
 

Fig. 8b: E/A & E/Ea in the three groups of patients with MS.

Left Ventricular Hypertrophy
Fig.9a shows the LV mass and adjusted indexes {LV mass/body surface (LVMi), LV mass/ height (LVMi-1) and LV mass/BMI (LVMI-2)} in the three groups. The mean LV mass and LV mass adjusted indexes for body surface, and BMI showed an increasing trend, with the lowest value in Group A (80.9 ± 21.3, 96.6 28.9, 4.7 ± 1.4), followed by Group B (98.1 ± 24.5, 107.1 26.6, 6.5 ± 1.9) and maximum value in Group C (105.5 ± 21.6, 111.2 ± 22.6, 7.0 ± 2.1) respectively. When comparing LV mass and its adjusted indexes to body surface, height and BMI between the groups especially group A with group B & C, p-value was statistically significant (p value < 0.05). The relative wall thickness (RWT) also showed an increasing trend from Group A to Group C, but was statistically insignificant.

Mean LV mass and LV mass adjusted indexes for body surface, and BMI were increased in males (193.5 ± 45.6, 106.3 ± 25.0, 115.6 ± 27, 67.4 ± 1.8) as compared to females (151.01 ± 31.0, 88.5 ± 19.4, 96.8 ± 19.6, 5.2 ± 1.5), and this difference was statistically highly significant (p value < 0.0001).

Fig.9b depicts the number of patients with Left Ventricular Hypertrophy (LVH) in the three groups along with pattern of hypertrophy. Of the total population 13 (13%) had no LV hypertrophy, 76 (76%) had concentric remodeling, of which 11 (85 %) in Group A, 45 (79%) in
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Group B and 20 (67%) in Group C. 11 (11%) had concentric hypertrophy of which 2 (15 %) in Group A, 4 (7 %) in Group B, 5 (17%) in Group C and none of the patients had eccentric hypertrophy.

Of the 54 males 5 (9.3%) had no LV hypertrophy, 42 (77.8%) had concentric remodeling, 7 (13.0%) had concentric hypertrophy and none of the males had eccentric hypertrophy. Of the 46 females 9 (19.6%) had no LV hypertrophy, 33 (71.7%) had concentric remodeling, 4 (8.7%) had concentric hypertrophy and none of the males had eccentric hypertrophy.

Fig.9a: Mean LVMI indexed to BSA, Ht & BMI in the three groups of patients with MS.

Fig.9b: Prevalence of patterns of LVH in the three groups of patients of MS.

Left Atrial Volume

Fig.10 shows Mean and Prevalence of LAVI in the three groups. The mean LAVI was abnormal in all the groups and showed an increasing trend with the lowest value in Group A (22.0 ± 3.6), followed by the Group B (23.5 ± 5.0), and highest for the Group C (25.5 ± 6.0). Of the total population 9 (9.0%) had abnormal LAVi, of which 5 (8.7%) in Group B, 9 (9.0%) in Group C. none of them had abnormal LAVi in Group A.

Of the 54 males, 5 (9.3%) had increased LAVi > 33 with a mean LAVi of 24.0 ± 5.5. Of the 46 females, 4 (8.7%) had increased LAVi > 30 with a mean LAVi of 23.8 ± 5.0.

Fig.10: Mean LAVi in the three groups of patients with MS.

 

Composite Initima Media Thickness

Fig.11a shows Mean and Prevalence of Composite IMT in the three groups. The Composite IMT showed an increasing trend with the lowest value in Group A (0.52 ± 0.09), followed by the Group B (0.73 ± 0.33), and highest for the Group C (0.81 ± 0.36). Of the total population 35% had abnormal Composite IMT, of which 19 (33.3%) in Group B, 16 (53.3%) in Group C. None of them had abnormal Composite IMT in Group A (Fig 11b).

Of the 54 males, 20 (37.0%) had increased

Fig.11a. Composite CCIMT in the three groups of patients with MS.

 

Fig. 11b: Prevalance of Composite CCIMT in the three groups with MS.

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Composite IMT with a mean IMT of 0.76 ± 0.39. Of the 46 females, 19 (41.3%) had increased Composite IMT with a mean IMT of 0.70 ± 0.23.

DISCUSSION

There is limited data regarding prevalence and prognostic significance of subclinical CVD in individuals with MS. Framingham Offspring Study39 investigated prevalence of subclinical CVD in 1,945 participants using electrocardiography, echocardiography, carotid ultrasound, ankle-brachial blood pressure, and urinary albumin excretion. They prospectively evaluated the incidence of CVD associated with MS and diabetes according to presence versus absence of subclinical disease. Cross-sectionally, 51% of 581 participants with MS had subclinical disease in at least one test, a frequency higher than individuals without MS (multivariable-adjusted odds ratio 2.06 [95% CI 1.67–2.55]; P < 0.0001). On follow-up (mean 7.2 years), 139 individuals developed overt CVD, including 59 with MS (10.2%). Overall, MS was associated with increased CVD risk (multivariable-adjusted hazards ratio [HR] 1.61 [95% CI 1.12–2.33]). Participants with MS and subclinical disease experienced increased risk of overt CVD (2.67 [1.62–4.41] compared with those without MS, diabetes, or subclinical disease), whereas the association of MS with CVD risk was attenuated in absence of subclinical disease (HR 1.59 [95% CI 0.87–2.90]). Individuals with MS were also found to have a high prevalence of subclinical atherosclerosis that contributes to the increased risk of overt CVD associated with the condition.
Various diagnostic modalities both invasive and non-invasive such as electrocardiography, echocardiography and radionuclide scans are utilized for diagnosing presence of subclinical CVD or target organ damage (as evidenced by left ventricular hypertrophy [LVH]40,41 LV dysfunction or atrial enlargement)
Our study evaluated echocardiographically derived measurements of LV structure and function in 100 subjects with MS, divided into three groups on the basis of age < 40 yrs, 40-60 yrs, and > 60 yrs respectively.
Metabolic syndrome and Left Ventricular Myocardial Performance Index

The Doppler-derived myocardial performance index (MPI) is a nongeometric and noninvasive assessment of global cardiac function including components from both systole and diastole. In our study we found mean LVMPI was prolonged in all the groups and showed an increasing trend from Group A to

Group C. Of the total study group, 74% had prolonged LVMPI with highest value in Group B (52.7 %). Majority of our patients with prolonged LVMPI had impaired LV diastolic function but normal LV systolic function. We found that there was a strong correlation between LVMPI & LVDD (p-value < 0.0001), which in turn shows LVMPI is the most robust marker of LVDD in patients with metabolic syndrome. And as all our patients with LVMPI value of greater than 0.62 had either grade II or grade III LVDD, indicating that this value can be used as the criterion for diagnosing the pseudonormal / restrictive mitral flow with normal systolic function and the sensitivity, specificity, and accuracy were  82%, 96%, and 91%, respectively.
LVMPI derived by 3D echocardiography can be used as a single-parameter indicator to describe a combined systolic-diastolic index for categorizing patients by disease state and possibly, severity and can be applicable in most echocardiographic laboratories as routine clinical practice. It is simple, easy-to-perform, noninvasive method that is not dependent on heart rate, preload, afterload, ventricular form, or movement. It provides a novel, objective parameter for detecting abnormal cardiac function at an early stage in patients with MS and may offer useful information about prognosis and therapeutic implications.

Metabolic syndrome and Left Ventricular hypertrophy

Metabolic syndrome (MS) is associated with increased prevalence of echocardiographic LV hypertrophy (LVH), a potent and independent predictor of cardiovascular (CV) outcome and identifies patients at high risk of future morbid events. The Strong Heart Study42 revealed that LVH is a strong predictor of composite 8-year fatal and non-fatal CV events either in the presence or in the absence of MS and accounts for a substantial portion of the high CV risk associated with MS. Gubbio Study43 results showed that MS is associated with increase in left ventricular mass and waist circumference, BP and blood glucose were the components of the syndrome with stronger impact on cardiac mass. Mamedov et al44 a russian study concluded that patients with MS had thicker left ventricular posterior wall and interventricular septum what was associated with increased end-systolic and end-diastolic dimensions as well as myocardial mass of the left ventricle and was associated with concentric left ventricular hypertrophy. But in our study we found that the mean LV mass adjusted indexes for body surface were normal in all the groups with an increasing trend from Group A to Group C and the comparison of LV mass indexes between the Group A vs Group B and the Group A vs Group C were statistically significant (p value < 0.05). Similar results were found with LVMI indexed to height and BMI. And males had higher LV mass as compared to females
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with very high statistical significance (p value < 0.0001). It is possible that these differences are due to the demographic characteristics which distinguish the population under study, such as age, sex, race, height, degree, type of distribution and duration of obesity or even the definition criteria for echocardiographic LV hypertrophy. LV mass is related to many factors like Rasooly et al45 have found that LV hypertrophy is more related to the waist or waist/hip ratio than BMI. In contrast, Bella et al42 have shown that LV mass is more strongly related to free fat mass by bioelectric impedance than other indexes such as BMI, height or waist/hip ratio. Sasson et al46 have described that LV mass was strongly associated with the degree of insulin resistance assessed using an index derived from intravenous glucose tolerance test, independent of BMI and blood pressure.
The pattern of LV hypertrophy observed in our study was concentric remodeling type, since there was no increase of LV mass but with increase in relative wall thickness. These results are similar to Sundstrom et al.47 which showed that MS was related to thick LV walls (increased RWT) and concentric remodeling but less to LV hypertrophy. These findings were somewhat unexpected, because some other studies have shown LVH to be related to MS 48,50. However, other studies have shown MS to be related to left ventricular concentric remodeling rather than to LVH49, 51-53  in accordance with the present study.
In summary, this report identified a strong relationship between metabolic syndrome abnormalities and LV mass, as measured by the echocardiogram, in middle-aged to elderly women and men. This relationship appeared to be equally strong in women and men. These findings are consistent with a possible influence of underlying factors such as insulin resistance and a hemodynamic or vascular process on myocardial thickening.

Metabolic syndrome and LV dysfunction

Results of the present study are consistent with those of prior studies that have evaluated the relationship between metabolic syndrome and echocardiographically derived measures of LV structure and function 15, 54-56. Lisa et al57. showed that individuals with metabolic syndrome had normal LV systolic function but frequently show abnormalities in LV diastolic function (i.e. impaired relaxation). Hisashi Masugata et al58 results revealed that patients with metabolic syndrome can have cardiac diastolic dysfunction even if they have neither LV hypertrophy nor systolic dysfunction. In the Strong Heart Study, those with metabolic syndrome had significantly lower E/A ratio. Azevedo A, et al59 showed that measures of left-ventricular diastolic dysfunction increased significantly with increasing numbers of metabolic syndrome features but, left ventricular systolic function was preserved. In the present study, in majority of the patients with MS, LV systolic function was preserved as the mean LVEF was normal in all the groups.

But 68% had impaired diastolic function of which majority of them had impaired LV relaxation (53%). None of the patients had grade IV diastolic dysfunction. We also found an inverse relationship between E/A ratio and E/E’ ratio. So our series of individuals with metabolic syndrome have normal LV systolic function but frequently showed abnormalities in LV diastolic function (i.e. impaired relaxation). These functional abnormalities may partially explain the increased cardiovascular morbidity and mortality associated with metabolic syndrome.
Metabolic syndrome and Left Atrial Volume index
As it is known that LAVi is a robust marker of atrial fibrillation, stroke, post-MI survival, CHF60-62 and has also been suggested as a marker of the severity and duration of diastolic dysfunction (DD)63. However, in our study group, mean LAVi was within normal limits and we found that although LAVi increased with worsening DD and was highly sensitive and specific for the detection of severe (grade III or IV) DD, it was not a robust marker of mild or moderate DD, which is common in majority of our patients. We speculate that chronic and severe elevation of filling pressures is needed to induce significant atrial remodeling and that the minimal or milder degree of atrial pressure elevation likely associated with grade I or II DD is insufficient to induce clearly abnormal LA volume. In contrast, severe elevation of atrial pressures indicated by advanced (grade III or IV) DD is more likely to have induced significant atrial remodeling making LA volume relatively sensitive for the detection of advanced DD. Thus, we can say that LAVi is a less robust marker of LVDD as compared to LVMPI as seen in our series of patients with MS.
Metabolic syndrome and Composite CCIMT

Carotid intima-media thickness (IMT) is a useful surrogate marker of cardiovascular disease. Studies have shown that subjects with MS are at increased risk for progressive carotid atherosclerosis62.  Kawamoto et al.63 showed that carotid IMT increased with increasing numbers of metabolic syndrome components (p value for trend < 0.001). J. K. Olijhoek et al65 showed that patients with MS had an increased mean IMT and an increase in the number of components of the metabolic syndrome was associated with an increase in mean IMT. Our study investigated the association between MS and carotid atherosclerosis and we found that the Composite CCIMT showed an increasing trend from Group A to Group C (p value for trend < 0.0001) and of the total patients 35% had increased Composite CCIMT. Our results also confirmed the known association
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between age and atherosclerosis. In all the analyses performed in the present study, age was significantly and markedly associated with presence and extent of carotid atherosclerosis and MS seemed to play a role in accelerating this age-associated process67.  The impact of the components of MS on carotid IMT differs between men and women. Iglseder et al68. showed that the effect of MS on early atherosclerosis is more pronounced in females. Our study demonstrated similar findings the increase being greater in men, but prevalence of increased composite CCIMT was more pronounced in females (p value < 0.0001)
Limitations
The present study has certain limitations. It is not a prospective cohort study and there was no long term follow up of the patients. There was no interobserver or intraobserver variability in our study. Since this was a hospital-based study, most of the patients were already on anti-hypertensives, oral hypoglycemic agents or on insulin therapy and on statin therapy.

Conclusion
Thus 3D echo has been recommended as the most promising and useful tool to predict occult CVD in patients of Metabolic Syndrome. It may therefore help us for early detection and timely effective therapeutic intervention to reduce CVD morbidity and mortality


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