The Association of Left Ventricular Mass Index with Metabolic Syndrome in Comparison to Hypertensive Patients.

BACKGROUND AND OBJECTIVES: The metabolic syndrome (MS) is a condition associated with the clustering of risk factors including high blood pressure (BP), abdominal obesity, glucose intolerance, and dyslipidemia; which increases cardiovascular morbidity and mortality. High burden of subclinical disease component of MS contributes to the increased risk by causing left ventricular (LV) hypertrophy, thereby affecting long-term prognosis. This cross-sectional study uncovers the role of LV hypertrophy (LVH) and LV mass index (LVMI) in patients with MS in comparison to hypertensive patients. SUBJECTS AND METHODS: A total of fifty North Indians, out of which 25 subjects were cases with the MS (obesity, dyslipidemia, glucose intolerance/diabetes with hypertension) and rest of the 25 subjects were control with hypertensive patients were included in the study and assessed for LVH and LVMI by two-dimensional echocardiography. Data were analyzed by SPSS version 21.0 based program.
RESULTS: MS cases had a significantly higher mean LVMI (49.60 ± 21.23 g/m2.7) (P < 0.05), also higher exposure rate of LVH with 11 cases (44%) and relative risk of 1.38 (odds ratio 1.67, 95% confidence interval 0.53-5.29) than controls with hypertensive patients. Among LVH patients, mean LVMI was highest in MS cases with males (50.31 ± 26.03 g/m2.7), high body mass index >30 kg/m2 (51.14 ± 22.08 g/m2.7), FBS ≤ 140 mg/dl (53.72 ± 27.91 g/m2.7), high TG > 150 mg/dl (50.00 ± 22.09 g/m2.7), and low HDL (male <40, female <50 mg/dl) (57.22 ± 27.23 g/m2.7) than controls with hypertension; respectively (P > 0.05, not significant).
CONCLUSION: MS, as a clustering of cardiovascular risk factors, is associated with higher LVM and prevalence of LVH. Therefore, high BP, increased waist circumference, dyslipidemia, and hyperglycemia separately and additively contributes to LVH suggesting that optimal BP control along with weight loss, lipid lowering agents, and euglycemic state may contribute to regression of LVH and LVM.

INTRODUCTION

Metabolic syndrome (MS) is a cluster of interrelated common clinical disorders, including obesity, insulin resistance, glucose intolerance, hypertension, and dyslipidemia, associated with a greater risk of atherosclerotic cardiovascular disease than any of its individual components.[1] MS represents a clustering of cardiovascular risk factors affecting 22% of the adult population in industrialized countries and over 40% of those ages 50 and older. Patients with MS having components, such as obesity, diabetes, hypertension and/or dyslipidemia, are also associated with increased left ventricular (LV) mass.[2] Asymptomatic LV systolic and diastolic dysfunction is correlated with MS and demonstrates that echocardiography is a useful tool to detect patients at high risk of heart failure. Echocardiography in asymptomatic patients with MS may lead to a therapy initiation at early stages to prevent future cardiovascular events and heart failure. Echocardiography can detect preclinical functional or structural myocardial abnormalities in asymptomatic subjects with two or more cardiovascular risks and without electrocardiogram (ECG) abnormalities, and can improve the prognostic impact in comparison to other settings (clinical, ECG). MS provides important risk information beyond that of established risk factors for heart failure.[1] The criteria for effects of MS components on cardiac structure and function have not been well studied. Even after controlling for age, sex, and 24-h systolic blood pressure (SBP); subjects with MS have significantly greater LV mass (LVM).[2] It is well documented nowadays the negative prognostic impact of LV hypertrophy (LVH) in terms of major cardiovascular events, including stroke and myocardial infarction and increased total mortality. Because of low sensitivity of ECG, it is crucial to identify LVH correctly by means of echocardiography.[3] The present cross-sectional study is undertaken to evaluate the association of LVH and LVM index (LVMI) in patients with MS (body mass index [BMI], lipid disorder, hyperglycemia with hypertension) in comparison to hypertensive patients.

SUBJECTS AND METHODS

Of 50 North Indians, 25 cases were of MS according to International Diabetes Federation (IDF) (2006) definition and 25 controls were essential hypertensive patients that do not fulfill IDF criterion of MS.[4] All subjects who had evidence of cardiovascular disease, including heart failure symptoms or systolic dysfunction (LV ejection fraction [LVEF] <55%), coronary artery disease (CAD), congenital heart disease, significant valvular heart disease (greater than mild valvular insufficiency or stenosis) and/or hypertrophic cardiomyopathy; pregnancy or lactating; and/or major systemic illness, were excluded from the study.

The IDF definition of the MS:[4] Central obesity (defined as waist circumference [WC] with ethnicity-specific values) for South Asians (male ≥90 cm and female ≥80 cm) and any two of the following:

Raised triglycerides (TGs): >150 mg/dl (1.7 mmol/L) or specific treatment for this lipid abnormality

Reduced high-density lipoprotein (HDL) cholesterol: <40 mg/dl (1.03 mmol/L) in males, <50 mg/dl (1.29 mmol/L) in females or specific treatment for this lipid abnormality

Raised BP: SBP > 130 or diastolic BP (DBP) >85 mmHg or treatment of previously diagnosed hypertension

Raised fasting plasma glucose (FPG): >100 mg/dl (>5.6 mmol/L) or previously diagnosed Type 2 diabetes. If FPG > 5.6 mmol/L or 100 mg/dl, oral glucose tolerance test is strongly recommended but is not necessary to define the presence of the syndrome (random blood sugar to assess glucose intolerance).

If BMI is >30 kg/m2, central obesity can be assumed, and WC does not need to be measured.

Echocardiography (LVH and LVM): Echocardiography was performed in harmonic imaging mode by use of a 3.5 MHz transducer and commercial ultrasound system (HD11XE Philips). The widely used Devereux formula treats the left ventricle as a cube so that the myocardial volume is the difference between the outer margin of the left ventricle and the cavity.[5] The cavity diameter is the LV end-diastolic dimension (LVIDd), and the outer diameter is the LVIDd plus the septal width (IVSWTd) plus the posterior wall width (PWTd) at end diastole. Mass is derived from volume after multiplying by the density of cardiac muscle, 1.04 g/cm3. By correlating calculated LVM with angiographic and postmortem findings, Krauser and Devereux derived a correction factor of 13.6 g, giving the formula LVM = 0.8 (1.04 [(LVID + IVSWTd + PWTd)3 − (LVIDd)3]) +0.6 g. Internal dimensions left ventricle wall thickness and LVEF were measured end diastole according to published recommendations.[5] The estimation of LVM was derived from LV measurements obtained by two-dimensional echocardiography.[6] LVM was normalized to height to allometric power of 2.7 to obtain LVMI. LVH was defined as LVMI equal to or higher than 51 g/m2.7 in men and 47 g/m2.7 in women.[7]

Systemic hypertension was recorded according to Joint National Committee VIII criteria, as BP ≥ 140/≥90 mmHg and/or current antihypertensive therapy.[8] Overweight and obesity were defined as a BMI between 25–30 kg/m2 and >30 kg/m2, respectively.[9] Glucose enzymatic colorimetric (glucose oxidase/peroxidase) method for fasting blood sugar (FBS) and enzymatic colorimetric cholesterol (cholesterol oxidase/peroxidase aminophenazone) method for serum lipid profile used. TG and HDL were detected by kit method from Merck (Merck category 15,760 and 14,210), respectively. Diabetes and impaired blood glucose was defined according to revised American Diabetes Association criteria, as random blood sugar test.[3] The data collected was analyzed by SPSS Version 21.0 (IBM, Armonk, New York, United States) based program.

RESULTS

Mean SBP (151.36 ± 14.33 mmHg; 160.24 ± 18.05 mmHg) as well as mean DBP (94.24 ± 7.73 mmHg; 99.44 ± 7.78 mmHg) was insignificantly decreased in cases than controls; respectively (P > 0.05). Mean BMI, WC and FBS were significantly increased in cases (32.30 ± 2.31 kg/m2, 92.72 ± 5.54 cm, 152.68 ± 32.64 mg%) than controls (25.92 ± 2.32 kg/m2, 80.42 ± 5.87 cm, 114.56 ± 9.53 mg%), respectively (P < 0.001) (P < 0.001) (P < 0.001). Mean serum TG was significantly increased in cases (172.00 ± 17.85 mg%) than controls (129.24 ± 18.64 mg%) while serum HDL was significantly lower in cases (48.96 ± 8.09 mg/dl) than controls (55.12 ± 5.10 mg/dl) (P < 0.001, P < 0.01) [Table 1].

Table 1

Baseline subjects characteristics and their comparison in both groups

Parameter	Mean±SD		P value significance (two-tailed)
	Metabolic syndrome (n=25)	Hypertension (n=25)
Age (years)	58.72±11.92	56.32±8.98	>0.05 (NS)
SBP (mmHg)	151.36±14.33	160.24±18.05	>0.05 (NS)
DBP (mmHg)	94.24±7.73	99.44±7.78	>0.05 (NS)
BMI (kg/m2)	32.30±2.31	25.92±2.32	<0.001
WC (cm)	92.72±5.54	80.42±5.87	<0.001
FBS (mg/dl)	152.68±32.64	114.56±9.53	<0.001
TG (mg/dl)	172.00±17.85	129.24±18.64	<0.001
HDL (mg/dl)	48.96±8.09	55.12±5.10	<0.010
LVM (g)	188.40±87.59	171.64±62.52	<0.05
LVMI (g/m2.7)	49.60±21.23	40.48±14.13	<0.05

SD=Standard deviation, SBP=Systolic blood pressure, DBP=Diastolic blood pressure, BMI=Body mass index, WC=Waist circumference, FBS=Fasting blood sugar, TG=Triglyceride, HDL=High density lipoprotein, LVM=Left ventricular mass, LVMI=Left ventricular mass index, NS=Not significant

The mean LVM and LVMI was affected in cases (188.40 ± 87.59 g, 49.60 ± 21.23 g/m2.7) significantly higher than controls (171.64 ± 62.52 g, 40.48 ± 14.13 g/m2.7); respectively (P < 0.05) [Table 1]. Exposure rate (ER) of LVH was higher with 11 cases in MS (44%) and relative risk (RR) of 1.38 (odds ratio [OR] 1.67, 95% confidence interval [CI] 0.53–5.29) than 8 controls of hypertensive patients (32%) [Table 2] and [Figure 1].

Table 2

Left ventricular hypertrophy distribution between patients with metabolic syndrome and hypertension

	Metabolic syndrome (n=25)	Hypertension (n=25)	RR	OR	95% CI
LVH	11	8	1.38	1.67	0.53-5.29
No LVH	14	17
ER (%)	44	32

LVH=Left ventricular hypertrophy, ER=Exposure rate, RR=Relative risk, OR=Odds ratio, CI=Confidence interval

Figure 1

Left ventricular hypertrophy distribution between patients with metabolic syndrome and hypertension

Mean LVMI was highest in MS cases with males (50.31 ± 26.03 g/m2.7), high BMI > 30 kg/m2 (51.14 ± 22.08 g/m2.7), FBS ≤ 140 mg/dl (53.72 ± 27.91 g/m2.7), high TG > 150 mg/dl (50.00 ± 22.09 g/m2.7), and low HDL (male < 40, female < 50 mg/dl) (57.22 ± 27.23 g/m2.7) than controls with hypertension; respectively (P > 0.05, not significant) [Table 3].

Table 3

Mean left ventricular mass index distribution in relation to risk factors between patients with metabolic syndrome and hypertension

Mean LVMI (g/m2.7) mean±SD	Metabolic syndrome (n=25)	Hypertension (n=25)	P value significance (two-tailed)
Male	50.31±26.03 (15)	40.99±13.85 (20)	>0.05 (NS)
Female	48.54±12.08 (10)	38.44±16.71 (5)
BMI (kg/m2)
>30	51.14±22.08 (22)	38.86 (1)	>0.05 (NS)
≤30	38.35±8.52 (3)	40.55±14.43 (24)
FBS (mg/dl)
>140	46.86±15.87 (15)	- (0)	>0.05 (NS)
≤140	53.72±27.91 (10)	40.48±14.13 (25)
TG (mg/dl)
>150	50.00±22.09 (23)	40.59±13.35 (3)	>0.05 (NS)
≤150	45.05±5.93 (2)	40.46±14.53 (22)
HDL (mg/dl)
Male <40, female <50	57.22±27.23 (10)	- (0)	>0.05 (NS)
Male ≥40, female ≥50	44.52±15.07 (15)	40.48±14.13 (25)

SD=Standard deviation, LVMI=Left ventricular mass index, BMI=Body mass index, FBS=Fasting blood sugar, TG=Triglyceride, HDL=High density lipoprotein, NS=Not significant

Among 19 LVH subjects, ER was higher for males with 6 cases in MS (54.5%, RR 0.72, OR 0.4, 95% CI 0.05–2.9), for high BMI (>30 kg/m2) with 11 cases in MS (100%, RR 17.3, OR 391, 95% CI 7.0–21757.5), for high FBS (>140 mg/dl) with 5 cases in MS (45.5%, RR 8.3, OR 14.4, 95% CI 0.7–309.9), for high TG (>150 mg/dl) with 10 cases in MS (90.9%, RR 7.3%, OR 70, 95% CI 3.7–1317.9) and for low HDL (male < 40, female < 50 mg/dl) with 5 cases in MS (45.5%, RR 8.25, OR 14.4, 95% CI 0.7–309.9) than controls with hypertension [Table 4] and [Figure 2].

Table 4

Left ventricular hypertrophy distribution in relation to risk factors between patients with metabolic syndrome and hypertension

LVH	Metabolic syndrome (n=11)	Hypertension (n=8)	ER (%)	RR	OR	95%CI
Male	6	6	54.5	0.72	0.4	0.05-2.9
Female	5	2
BMI (kg/m2)
>30	11	0	100	17.3	391	7.0-21757.5
≤30	0	8
FBS (mg/dl)
>140	5	0	45.5	8.3	14.4	0.7-309.9
≤140	6	8
TG (mg/dl)
>150	10	1	90.9	7.3	70	3.7-1317.9
≤150	1	7
HDL (mg/dl)
Male <40, female <50	5	0	45.5	8.25	14.4	0.7-309.9
Male ≥40, female ≥50	6	8

LVH=Left ventricular hypertrophy, BMI=Body mass index, FBS=Fasting blood sugar, TG=Triglyceride, HDL=High density lipoprotein, ER=Exposure rate, RR=Relative risk, OR=Odds ratio, CI=Confidence interval

Figure 2

Left ventricular hypertrophy distribution in relation to risk factors between patients with metabolic syndrome and hypertension

DISCUSSION

Cardiovascular risk factors in MS have been shown to act synergistically, via mechanisms poorly defined, to increase the risk of adverse cardiovascular events, including CAD and congestive heart failure, also associated with high cardiovascular morbidity and mortality. Although studies have shown that hypertension, diabetes mellitus, and obesity adversely affect cardiac structure and function, the extent to which individual and clustering components of the MS predict subclinical LV systolic and/or diastolic dysfunction has not been well characterized. LVH is a maladaptive response to chronic pressure overload and an important risk factor for atrial fibrillation, diastolic heart failure, systolic heart failure, and sudden death in patients with hypertension. LVH imparts increased risk of cardiovascular morbidity and mortality, including the development of systolic and diastolic dysfunction and progression to heart failure.[101112] LVH is one of the complications and is, in turn, an important risk factor for myocardial infarction, heart failure, stroke, and cardiac sudden death.[13] Complications of LVH include atrial fibrillation, diastolic/systolic heart failure, and sudden death. Both earlier recognition and improved understanding of cardiac hypertrophy may lead to more effective therapeutic strategies for this cardiovascular risk factor.[14]

It is now appreciated that LVH is mediated not only by the mechanical stress of pressure overload but also by various neurohormonal substances that independently exert trophic effects on myocytes and nonmyocytes in the heart.[15] BP is the main determinant of the hemodynamic workload for the left ventricle and in turn, of LVM although both hemodynamic and nonhemodynamic factors are involved in the complex pathogenesis of LVH.[16]

Since not all patients with hypertension develop LVH, there are clinical findings that should be kept in mind that may alert the physician to the presence of LVH so a more definitive evaluation can be performed using an echocardiogram or cardiovascular magnetic resonance imaging.[13] The lack of a linear association between LVM and BP suggests other factors such as insulin resistance and hyperinsulinemia, sodium retention, sympathetic activation, and adipose tissue peptides such as leptin may be responsible in patients with MS.

In this cross-sectional study, total 50 North Indians, in which 25 cases of MS and 25 controls of hypertensive patients were compared for LVH and LVMI. Patients with MS shows significantly higher mean LVM and LVMI (188.40 ± 87.59 g, 49.60 ± 21.23 g/m2.7) than hypertensive patients (171.64 ± 62.52 g, 40.48 ± 14.13 g/m2.7); respectively (P < 0.05) [Table 1].

Left ventricular mass index with hypertension

This study showed that patients with MS have higher ER of LVH with 11 cases (44%) and RR of 1.38 (OR 1.67, 95% CI 0.53–5.29) than hypertensive patients with 8 controls (32%) only [Table 2] and [Figure 1]. It also points to mean SBP for hypertensive patients is higher (160.24 ± 18.05 mmHg) than patients having MS. Hypertension is commonly associated with the LVH since Lokhandwala and Damle found that out of 86 Indian patients recruited, 21 (24.4%) had LVH.[17]

Left ventricular mass index with gender

This study has showed that among MS patients males have highest mean LVMI (50.31 ± 26.03 g/m2.7) than females (48.54 ± 12.08 g/m2.7) and among hypertensive patients lesser in males (40.99 ± 13.85 g/m2.7) than least in females (38.44 ± 16.71 g/m2.7) [Table 3]. Among LVH subjects, ER was higher for males with 6 cases in MS (54.5%, RR 0.72, OR 0.4, 95% CI 0.05–2.9) than females (ER 45.5%). Similarly, Cuspidi et al. Has shown a gender-related difference, in terms of a slight, nonsignificant higher prevalence of LVH in women 47.4% and men 45.6%, moreover in overweight and obese women than men.[7]

Left ventricular mass index with body mass index

Obesity is a worsening epidemic in Western and developing countries, leading to increasing morbidity and mortality. Obesity promotes hemodynamic changes, i.e., increased cardiac output and lower peripheral vascular resistance, in the absence of overt hypertension. Increased cardiac output, with little changes of heart rate, leads to LV remodeling.[3] Super obesity is associated with insulin resistance, with a worse impact on cardiac remodeling and LV diastolic function than morbid obesity.[1] Obese patients are 30% more likely to develop heart failure and each 1 kg/m2 rise of BMI increases the risk of heart failure by 5% for men and by 7% for women. Long-term obesity is associated with early diastolic dysfunction, LVH, and LV dilatation, resulting finally in cardiac failure. Potential mechanism that might contribute to the pathogenesis of cardiac dysfunction in obesity includes accommodation of lipid in or around myocytes producing lipotoxicity, insulin resistance, and neuroendocrine activation. Ventricular remodeling is common, with LV eccentric hypertrophy developing in response to the expanded intravascular volume present in obesity. After the load is elevated due to elevated vascular resistance caused by excess adipose tissue and higher artery stiffness.[18] This study has showed that high BMI increases LVMI since MS patients with BMI > 30 had highest mean LVMI (51.14 ± 22.08 g/m2.7) than MS patients with BMI < 30 had least (38.35 ± 8.52 g/m2.7) [Table 3]. Schirmer et al. have showed that weight reduction is a relevant measure for treatment and possibly prevention of LVH in a substantial part of the general population and concluded that BMI is the culprit factor for risk of LVH.[19] Okpara et al. have demonstrated that obesity is associated with increased LV wall thickness (lVS WTd and PWTd), increased LV internal diameter (LVIDd), increased LVM and LVH.[20] The mechanism of cardiac hypertrophy in obesity involves both hemodynamic and metabolic factors. Obesity produces an increase in total blood volume and cardiac output caused by the increased metabolic demand induced by excess body weight. This leads to ventricular chamber dilation, increase in wall stress, myocardial mass, and LVH.

Left ventricular mass index with hyperglycemia

The role of insulin resistance, as an important risk factor for the development of hypertension, atherosclerotic heart disease, LVH and heart failure reflecting that a disturbance of glucose metabolism may potentially worsen metabolic efficiency of both skeletal muscle and cardiac muscle. Insulin resistance might be promoted by a symptomatic nervous system overactivity, characterizing chronic heart failure and that this neurohormonal disregulation could be potentiated by obesity and MS.[1] In uncomplicated asymptomatic diabetic patients, the presence of first-degree obesity plays an incremental role in adversely affecting LV function and remodeling. The longitudinal subendocardial fibers dysfunction in diabetes/obese patients could be derived by the complex interaction between metabolic (diabetes) and hemodynamic/endocrine abnormalities.[18] In the present study, hyperglycemia has shown to increase the LVMI since MS patients with mean FBS ≤ 140 mg/dl had highest mean LVMI (53.72 ± 27.91 g/m2.7) than hypertensive patients (40.48 ± 14.13 g/m2.7) [Table 3]. Grossman et al. found that DM accelerates the development of LVH in patients with essential hypertension independent of arterial pressure and therefore, may contribute to the increased cardiovascular morbidity and mortality in patients with hypertension.[21]

Left ventricular mass index with lipid disorder

In this study, dyslipidemia has shown to increase the LVMI since MS patients with hypertriglyceridemia (>150 mg/dl) and low HDL (male < 40, female < 50 mg/dl) had highest mean LVMI (50.00 ± 22.09 g/m2.7, 57.22 ± 27.23 g/m2.7) than hypertensive patients with normal TG (≤150 mg/dl) and HDL (male ≥ 40, female ≥ 50 mg/dl) had least mean LVMI (40.46 ± 14.53 g/m2.7, 40.48 ± 14.13 g/m−2.7); respectively [Table 3]. Dyslipidemia, as well as hypertension, may be important in the origin of LVH.[22] Sundström et al. in prospective longitudinal cohort study has found that dyslipidemia, indices of a low dietary intake of linoleic acid and high intake of saturated and monounsaturated fats as well as hypertension and obesity at age fifty predicted the prevalence of LVH 20 years later, thereby suggesting that lipids may be important in the origin of LVH.[22]

However, limitations of this study are a small number of subjects, single center data, and retrospective screening only. This area of research needs further attention of physicians and cardiologists, looking to the highly prevalent MS in Indian community as a cluster of risk factors and its impact on LVMI, therefore; a large, prospective, double-blind study can be planned at various centers.

CONCLUSION

The combination of various components of MS is associated with higher LVMI and prevalence of LVH. Therefore, MS with dominant dyslipidemia, glucose intolerance, and obesity along with hypertension play an important role in causation of increased LVMI. High BP, increased WC, dyslipidemia and hyperglycemia separately and additively contributes to LVH suggesting that optimal BP control along with weight loss, lipid lowering agents, and euglycemic state may contribute to regression of LVH and LVMI.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.