Journal Of Indian College Of Cardiology

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 9  |  Issue : 2  |  Page : 100--104

The relation between insulin resistance and left ventricular mass in hypertensive nondiabetic patients


Ahmed Shawky Shereef, Nader Talat Kandeel 
 Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Correspondence Address:
Dr. Ahmed Shawky Shereef
Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig
Egypt

Abstract

Background: Patients with essential hypertension (EH) are often associated with left ventricular (LV) hypertrophy (LVH) and insulin resistance (IR). Insulin may have a direct growth-promoting effect on cardiomyocytes. Hence, the aim of this work was to study the effect of IR on LV geometry in newly diagnosed arterial hypertensive nondiabetic patients not taking any antihypertensive medication. Methods: One hundred and eight patients were included in our study including 88 newly diagnosed hypertensive nondiabetic patients and 20 healthy controls. Fasting glucose, insulin levels, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol, and triglyceride levels were measured. Homeostasis Model Assessment (HOMA) index was calculated for the assessment of IR. Echocardiography measurements of LV dimensions such as LV mass (LVM) and LVM index (LVMI) were calculated. Results: Fasting blood insulin and HOMA index were significantly higher in patients with LVH than patients with normal LV dimensions and controls. We found highly significant positive correlations between insulin levels, LVM, and LVMI. In addition, we found highly significant positive correlations between HOMA index, LVM, and LVMI. Conclusion: We conclude that cardiac changes in hypertensive patients including those with increased wall thickness, LVM, and LVMI are mediated, at least in part, by increased insulin levels and the HOMA index.



How to cite this article:
Shereef AS, Kandeel NT. The relation between insulin resistance and left ventricular mass in hypertensive nondiabetic patients.J Indian coll cardiol 2019;9:100-104


How to cite this URL:
Shereef AS, Kandeel NT. The relation between insulin resistance and left ventricular mass in hypertensive nondiabetic patients. J Indian coll cardiol [serial online] 2019 [cited 2019 Nov 13 ];9:100-104
Available from: http://www.joicc.org/text.asp?2019/9/2/100/267492


Full Text



 Introduction



Both left ventricular (LV) hypertrophy (LVH) and hyperinsulinemia/insulin resistance (IR) are known independent cardiovascular risk factors.[1],[2] A wide variety of LV geometry has been found in general population samples and in patients with essential hypertension (EH).[2]

In obese patients, arterial hypertension contributes significantly to LV diastolic dysfunction before detecting structural changes by echocardiography.[3]

Hypertension is an essential stimulus for the development of LVH. However, LV mass (LVM) increases in some hypertensive patients, whereas it remains within normal limits in others.[4] On the other hand, some nonhemodynamic factors such as genetic, environmental, and metabolic factors have also been suggested to affect LVM and geometry.[5],[6]

The metabolic factors include the presence of IR which has been found to be associated with LV growth.[7] Homeostasis Model Assessment (HOMA) is a method that allows an easy and inexpensive assessment of IR.[8]

 Aim of the Work



The aim of the work was to examine the effect of IR on LV geometry in newly diagnosed arterial hypertensive (NDAH) nondiabetic patients not taking any antihypertensive medication.

 Methods



This study had been carried out in the Cardiology Department of Zagazig University Hospitals during the period between January, 2016, and August, 2017.

One hundred and eight patients (66 males and 42 females) with a mean age of 48.9 ± 4.67 years were enrolled in the study including 88 newly diagnosed hypertensive patients (54 males and 34 females) and 20 healthy controls.

All the patients were newly diagnosed hypertensive patients. Hypertension was defined as elevation of blood pressure ≥140 mmHg for systolic and/or ≥90 mmHg for diastolic blood pressure as the mean of three different measurements in at least three different visits at 1-week interval.[9]

Exclusion criteria were a family history of diabetes, obesity (body mass index must be <30 kg/m2), coronary artery disease, congestive heart failure, valvular heart disease, impaired glucose tolerance, and diabetes mellitus. All patients were free from cardiac medications and drugs known to interfere with glucose metabolism.

Blood samples were taken after 10 h of overnight fasting to measure both fasting glucose and insulin levels. Fasting insulin concentrations were measured by radioimmunoassay. In the same sitting, serum samples were withdrawn to determine fasting total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels. HOMA was calculated for the assessment of IR. The HOMA index was calculated according to the formula developed by Matthews, et al.[8] as follows:

Fasting blood glucose (mg/dl) × fasting insulin (μ/ml)/405

Echocardiographic studies were performed on each patient using a commercially available Hewlett Packard 5500 (HP 5500, Sonos 5500, Boston, MA, USA) echo-set using a 2.5 MHz transducer. Two-dimensional guided M-mode measurements of LV end-diastolic dimension (LVEDD), interventricular septum thickness (IVST), posterior wall thickness (PWT), left atrial diameter, fraction of shortening (FS), and ejection fraction were performed as recommended by the American Society of Echocardiography.[9]

LVM was calculated according to the equation of Devereux et al. as follows:[10]

0.80× ([1.04× [LVEDD + IVST + PWT] 3 – [LVEDD] 3) +0.6 g

LVM was indexed by body surface area; LVH was defined as an LVM index (LVMI) of 125 g/m2 in men and 110 g/m2 in women.[11]

According to LVMI, hypertensive patients were classified into two groups: normal and LVH. Hence, we had the following three groups in our study:

Hypertensive patients with normal LV dimensions: this group included 46 patients (28 males and 18 females) with a mean age of 48.6 ± 3.55 yearsHypertensive patients with LVH: this group included 42 patients (26 males and 16 females) with a mean age of 49.8 ± 3.72 yearsHealthy controls: This group included 20 controls (12 males and 8 females) with a mean age of 47.7 ± 7.74 years.

Statistical analysis

All statistics were analyzed using the SPSS (SPSS 11.0 for windows Student version) 11.5 package program. Differences among the study groups were analyzed by Student's t-test and Chi-square test. The correlations among the HOMA index, insulin levels, and LV measurements were investigated by Pearson's correlation analysis. P <0.05 was regarded as being statistically significant.

 Results



We enrolled 108 individuals (66 females and 42 males) in this study; among them, 20 were healthy controls and 88 were patients with untreated newly diagnosed mild-to-moderate hypertension (151.5 ± 5.37 mmHg for systolic and 97.8 ± 3.78 mmHg for diastolic blood pressure).

As shown in [Table 1], there was no significant difference among the study groups concerning the clinical data, except for a highly significantly systolic and diastolic blood pressure in normal and LVH groups than control group.{Table 1}

Metabolic data are shown in [Table 2]. Fasting blood insulin and HOMA index were significantly higher in patients with LVH than in patients with normal LV dimensions and controls. Other metabolic data showed no significant difference among the study groups.{Table 2}

Echocardiographic data are shown in [Table 3]. As shown, PWT, IVST, LVM, and LVMI were significantly higher in patients with LVH than in patients with normal LV dimensions and controls. Other measures showed no significant difference among the study groups.{Table 3}

Pearson's correlation analysis performed among the insulin levels and echocardiographic measurements showed highly significant positive correlations between insulin levels and IVS (r = 0.35, P = 0.00083), PWT (r = 0.338, P = 0.00128), LVM (r = 0.367, P = 0.00044), and LVMI (r = 0.374, P = 0.00033), as shown in [Table 4].{Table 4}

Again, Pearson's correlation analysis was performed among the HOMA index and echocardiographic measurements, which revealed highly significant positive correlations with IVS (r = 0.759, P < 0.00001), PWT (r = 0.783, P < 0.00001), LVM (r = 0.702, P < 0.00001), and LVMI (r = 0.79, P < 0.00001) as shown in [Table 4].

Correlations of HOMA index with LVM and LVMI are shown in [Figure 1]a and [Figure 1]b.{Figure 1}

There was no significant correlation between insulin level or HOMA index and other echocardiographic parameters.

 Discussion



Both LVH and hyperinsulinemia/IR are known independent risk factors for cardiovascular diseases[1],[2] and have often been found in patients with EH. A wide variety of LV geometry has been found in general population samples and in patients with EH.[2]

Our study confirms that there is an association between insulin action and degree of LVM and also shows that patients with a normal LV pattern have a significantly better insulin action (lower fasting insulin levels and lower HOMA index) compared with those with abnormal LV geometry. Our study also shows significant positive correlations between IVST, PWT, LVM, LVMI (echocardiographic parameters of LVH), and IR, measured with fasting plasma insulin levels and the HOMA index (which is an IR parameter) in hypertensive patients.

There was no significant correlation between insulin level or HOMA index and LVEDD.

The correlations between measures of IR and LV structure have been studied in different populations with varying results. Significant relationships between IR and LVM have been reported in hypertensive populations.[12]

However, other investigators have only found a weak correlation between these parameters[13] or no association at all[14] after adjustments for covariates.

Furthermore, a change in the echocardiographic patterns from normal to concentric hypertrophy, including concentric remodeling, is associated with a trend toward IR.[4]

Previous studies have concluded that LVH has a bad prognosis for hypertension. In fact, patients with increased LVM have a greater risk of cardiovascular and all-cause mortality than those with lower LVM.[1] Krumholz et al.[15] have demonstrated a high risk of cardiovascular adverse events in patients with concentric LVH and a low risk in those with normal LV geometry, and this difference widened progressively over a 10-year follow-up, despite conventional antihypertensive therapy.

Epidemiological studies have shown that high fasting insulin levels are associated with an adverse cardiovascular outcome, independent of other risk factors,[2] and this could be explained in part by a remodeling effect by insulin on LV structure.

It has been proposed that insulin may affect cardiac geometry by acting as a growth-promoting factor, and its trophic effects on myocardial tissue have been demonstrated in cell cultures and animal models.[16]

Moreover, it has been suggested that hyperinsulinemia stimulates sympathetic nervous system (SNS) activity[17] which may affect ventricular structure directly due to growth-stimulating effects, or, indirectly, by the increment in both heart rate and blood pressure levels.

Such data support the hypothesis that the reason for the increase in wall thickness, which is a sign of myocardial structural change, and in part LVH itself in hypertensive patients, might be the increased fasting insulin levels and HOMA index, which is an indicator of IR. Many pathophysiologic factors could be behind such an association, and an insulin-mediated overdrive in SNS activity should be considered.[17]

Kaftan et al.[3] found that the positive correlation between insulin levels and the HOMA index was substantially stronger with the sum of wall thickness and relative wall thickness than the LVMI, and they concluded that insulin acts through increases in wall thicknesses, rather than an increase in LVED during the LV geometric change process in hypertensive patients, although recent studies reported that abnormalities of LV filling precede detectable structural changes and impairment of systolic function. They are considered one of the earliest signs of cardiac involvement in the presence of different cardiovascular risk factors.[18] NDAH also plays an important role in LV diastolic dysfunction pathogenesis.[19]

Another hypothesis is SNS overdrive is responsible for both IR and development of LVH.[20] In fact, hypertensive patients with LVH had higher plasma catecholamine concentrations than hypertensive patients without LVH and controls.[17]

On the other hand, our findings suggest that IR exerts its influence directly on myocardial walls, independently of LVED. Hyperinsulinemia might increase LVM through its growth-stimulating effect. In fact, insulin can bind and activate the insulin-like growth factor-1 receptor, leading to increased DNA and protein synthesis as well as cell proliferation in many tissues.[21] In particular, it has been demonstrated that insulin stimulates both proliferation of vascular smooth cells and cardiomyocyte hypertrophy by increasing mRNA levels for muscle-specific genes (myosin light chain, O-actin, and troponin I) and stimulating protein synthesis.[21]

Therefore, it is plausible that hyperinsulinemia in hypertension could stimulate SNS activity, which may, in turn, affect ventricular structure directly, due to growth-stimulating effects, or, indirectly, by contributing to increases in heart rate and blood pressure levels.

However, further studies are required in order to demonstrate the association between IR, compensatory hyperinsulinemia, and alteration in cardiovascular structure.

 Conclusion



The increased insulin levels and the HOMA index appear, at least in part, to mediate the concentric LV geometry in hypertensive patients.

Hence, the present results indicate that measurement of serum insulin levels and calculation of the HOMA index could provide a clue into the pathogenesis of different LV geometries in patients with mild-to-moderate EH.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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