Study of carotid intimal medial thickness in essential hypertension with or without left ventricular hypertrophy.

INTRODUCTION: Hypertension and atherosclerosis though separate entities, are interrelated as hypertension plays an important role in the pathogenesis of atherosclerosis. This study was undertaken to study the association of carotid intimal medial thickness with left ventricular hypertrophy (LVH) in hypertensive patients.
MATERIALS AND METHODS: Hundred hypertensives (JNC-7, Stage 1 and 2) between 30 and 55 years were enrolled in this prospective observational study conducted at a tertiary care teaching institute of Punjab, India. Electrocardiogram, Carotid Doppler, and Echocardiography were carried out in addition to routine biochemical investigations.
RESULTS: Increased carotid intimal medial thickness (CIMT) had statistically significant association with age, duration of hypertension, high systolic and diastolic blood pressure (BP), left ventricular hypertrophy and left ventricular mass index but was not associated with body mass index, low-density lipoproteins, and total cholesterol.
CONCLUSIONS: LVH and arterial wall changes occur concurrently, and therefore, management of hypertension should not be limited just to control of BP but should also include therapy for carotid plaques and increased CIMT.

INTRODUCTION

Hypertension is one of the leading causes of global burden of disease.[1] It is an important public health challenge in both economically developing and developed countries.[2] Hypertension doubles the risk of cardiovascular diseases, including coronary heart disease, congestive heart failure, ischemic and hemorrhagic stroke, renal failure, and peripheral arterial disease.[3] Complications of hypertension are either due to sustained elevation of blood pressure (BP) (with consequent changes in the vasculature and heart) or due to atherosclerosis that accompanies it.[3] Hypertension and atherosclerosis are two distinguished entities, but hypertension plays an important role in the pathogenesis of atherosclerosis.[45] It has been demonstrated that wall shear stress; frictional force produced by circulating blood column plays an important role in the progression of atherosclerosis.[6] In patients with hypertension, concentric hypertrophy is most commonly observed. Reversal of the left ventricular hypertrophy (LVH) appears to improve the prognosis, and reduction in BP is an important component in the regression of LVH. Thus, early identification and initiation of treatment prove beneficial in cases of hypertension.[7] The aim of this study was to evaluate the association between carotid intimal medial thickness and LVH in hypertensive patients.

MATERIALS AND METHODS

Hundred hypertensive patients as per JNC7 criteria Stage 1 and 2 were enrolled in this study. This prospective observational study was conducted in a tertiary care teaching hospital of Punjab. After the informed consent, detailed history and clinical examination were carried out on all patients. Patients with primary hypertension between 30 and 55 years of age were included in the study and those with secondary hypertension, smokers, diabetes, coronary artery disease, stroke, peripheral vascular disease, and collagen vascular disorders were excluded from the study. BP was recorded using sphygmomanometer. In all the patients, two readings were taken at the same visit, in sitting position in the right arm with 10–15 min interval by the same investigator. Blood urea, fasting blood sugar and postprandial blood sugar, serum creatinine, and lipid profile were done using standard laboratory techniques. Height (in m) and weight (in kilograms) were measured, and body mass index (BMI) was calculated using the formula weight (kg)/height (m2).

Electrocardiogram

Twelve lead electrocardiogram (ECG) was done to exclude any major coronary artery disease and to evaluate for LVH as per the Romhilt and Estes point score system.[8] A score of 5 or more indicated LVH and correlated with increased ventricular mass.

Carotid ultrasonography

The intimal medial thickness of common carotid artery was determined by high-resolution B mode ultrasonography with a high frequency (7.5MHz) linear transducer on Philips Envisor. The common carotid was visualized at 1 cm proximal to its bifurcation, and common carotid intimal medial thickness was measured in the far wall. Three values were averaged to give mean common carotid intimal medial thickness value for each patient.

Echocardiography

Echocardiography was performed by harmonic imaging mode on Alpha Prosound 6-Aloka Doppler machine according to the standard protocol. M-mode tracings were quantified according to the recommendation of the American Society of Echocardiography. Left ventricular diastolic indices were assessed by echo-pulsed Doppler analysis. Left ventricular mass index (LVMI) >51 g/m2 was taken as the criteria for LVH.[9]

The data collected was analyzed statistically using Chi-square test and student t-test. P < 0.05 was considered as statistically significant.

RESULTS

Of the hundred patients, 52 were males and 48 were females. The mean age of the patients was 49.7 years. Out of hundred patients, sixty-one patients were in Stage 1 and thirty-nine patients were in Stage 2. Thirty-four patients had hypertension of ≤5 years duration, thirty-eight patients of 6–10 years, and twenty-eight patients of more than 10 years. Low-density lipoprotein (LDL) was found to be more than 130 mg/dl in twenty-eight patients and the remaining seventy-two, the levels were normal. Total cholesterol (TC) was found to be elevated in thirty-nine patients out of hundred. BMI of more than 25 kg/m2 was found in fifty-four patients, and the remaining forty-six were found to have BMI of <25 kg/m2. ECG score of more than or equal to 5 suggestive of LVH was observed in thirty-one patients out of hundred and similarly LVMI of more than 51 g/m2.7 was present in thirty patients. Carotid intimal medial thickness of more than 0.8 mm was present in sixty-one patients and the remaining thirty-nine; it was <0.8 mm. Twenty-one patients were found to have plaques in the carotid arteries [Table 1].

Table 1

Baseline characteristics

Parameters	Present (number of subjects)	Absent (number of subjects)
LDL (>130 mg/dl)	28	72
TC (>200 mg/dl)	39	61
BMI (≥25 kg/m2)	54	46
ECG (RH score ≥5)	31	69
LVMI (>51 g/m2.7)	30	70
CIMT (>0.8 mm)	61	39
Plaque	21	79

LDL=Low-density lipoprotein, TC=Total cholesterol, BMI=Body mass index, LVMI=Left ventricular mass index, CIMT=Carotid intimal medial thickness, ECG=Electrocardiogram, RH=Romhilt-Estes point score system

The increased CIMT had statistically significant association with age (mean age 49.7 ± 4.7 years), duration of hypertension (mean 9.5 ± 3.9 years), high systolic BP (mean 157 ± 8.7 mmHg), high diastolic BP (mean 94 ± 6 mmHg), and LVMI (mean 50.9 ± 20 g/2.7). Increased CIMT was not found to have any statistically significant relation with BMI (mean 25.6 ± 2.5 kg/m2), LDL (mean 119.8 ± 37.9 mg/dl), and TC (mean 192.7 ± 41.4 mg/dl). Furthermore, it was found that LVH had statistically significant association with higher age (mean age 50.8 ± 4.2 years), increasing the duration of hypertension (mean 10.8 ± 3.8 years), high systolic BP (mean 160.2 ± 7.9 mmHg), and high diastolic BP (mean 96 ± 6.9 mmHg), and increased CIMT (mean 1.07 ± 0.24 mm). LVH was not found to have any statistically significant relation with BMI (mean 25.8 ± 2 kg/m2), LDL (mean 113 ± 31 mg/dl), and TC (mean 186.2 ± 42.7 mg/dl) [Tables 2 and 3].

Table 2

Mean parameters in subjects with and without left ventricular hypertrophy

Parameters	LVH		P
	Present	Absent
Age (years)	50.8±4.2	45.4±7.1	<0.001
Duration of hypertension (years)	10.8±3.8	6.8±4	<0.001
Systolic BP (mmHg)	160.2±7.9	151±9.1	<0.001
Diastolic BP (mmHg)	96±6.9	90±5.4	<0.001
BMI (kg/m2)	25.8±2	25±2.5	0.076
LDL (mg/dl)	113±31	116±46.5	0.699
TC (mg/dl)	186.2±42.7	195.2±62	0.403
CIMT (mm)	1.07±0.24	0.8±0.11	<0.001

LDL=Low-density lipoprotein, TC=Total cholesterol, BMI=Body mass index, CIMT=Carotid intimal medial thickness, BP=Blood pressure, LVH=Left ventricular hypertrophy

Table 3

Mean parameters in subjects with and without increased carotid intimal medial thickness (>0.8 mm)

Parameters	CIMT		P
	>0.8 mm	≤0.8 mm
Age (years)	49.7±4.7	42.8±7.4	<0.001
Duration of hypertension (years)	9.5±3.9	5.5±3.7	<0.001
Systolic BP (mmHg)	157±8.7	148±8.8	<0.001
Diastolic BP (mmHg)	94±6	89±4.8	<0.001
BMI (kg/m2)	25.6±2.5	24.7±2.3	0.06
LDL (mg/dl)	119.8±37.9	107.9±48.2	0.10
TC (mg/dl)	192.7±41.4	192.1±75.5	0.96
LVMI (g/m2.7)	50.9±20	32±9.9	<0.001

LDL=Low-density lipoprotein, TC=Total cholesterol, BMI=Body mass index, LVMI=Left ventricular mass index, CIMT=Carotid intimal medial thickness, BP=Blood pressure

DISCUSSION

The present study showed slightly male preponderance consisting of 52% males and 48% females. The prevalence of hypertension increased with age as maximum number of patients belonged to age group of 41–55 years. It was also found that 54% of the patients were obese with BMI more than 25 kg/m2. Similar findings were reported by Das et al.[10] and Kokiwar et al.[11]

The present study showed a statistically significant association between increased carotid intimal medial thickness with increasing age, being 87.5% cases in the age group of 51–55 years as compared to 26.3% in the age group of 31–40 years. Gender had no significant effect of CIMT, and these observations were consistent with the previous studies.[1213141516]

The present study showed that increased CIMT was associated with increased duration of hypertension (P < 0.001) and stage of hypertension (P < 0.002). Similar results were observed in the studies conducted by Nand et al.,[12] Heiss et al.,[13] and Zanchetti et al.[17]

In this study, there was a positive association of CIMT and high diastolic BP (P < 0.001), however, the work done by Zanchetti et al.[17] and Nand et al.[12] concluded a significant association of CIMT with systolic BP but no significant association with diastolic BP.

The present study revealed a positive association of LVH with increasing age (P < 0.003), stage of hypertension (P < 0.005), and duration of hypertension (P < 0.001). The results were consistent with a study conducted by Conrady et al.[18] Plaques were present in 27.9% of the cases with increased CIMT with statistically significant P = 0.035. This observation was in agreement with a study conducted by Bonithon-Kopp et al.[19] which also observed that plaques developed more frequently in women with increased CIMT rather than in women with normal CIMT. Previous observational studies conducted by Zanchetti et al.,[17] Heiss et al.[13] and Bonithon-Kopp et al.[19] revealed a positive association between increased CIMT and increased LDL, TC and increased BMI but in our study, it was seen that increased CIMT was neither associated with LDL and TC levels nor with increased BMI. This is probably because the absolute and mean values of both LDL and TC were in the normal range. The present study showed that 43.3% of the cases with LVH had plaques while 11.4% of the cases without LVH had plaques, which is similar to the study results of Roman et al.[20] that showed LVH was twice as likely to have carotid atheromas (35% vs. 18%, P < 0.01).

It was found in the studies conducted by Zanchetti et al.,[17] Heiss et al.[13] and Bonithon-Kopp et al.[19] that there is a positive association between increased CIMT and increased LDL and TC and increased BMI (≥25 kg/m2) but in our study, it was seen that increased CIMT (>0.8 mm) was not associated with LDL and TC levels and increased BMI (≥25 kg/m2). Cuspidi et al.[21] also found that TC has the greatest impact on IM thickening.

A positive association between the carotid intimal thickness and LVH was obtained by echocardiography. Out of sixty-one patients with increased carotid intimal thickness, LVH was present in twenty-eight patients (45.9%) with P < 0.001, and in patients with a normal carotid intimal thickness, only two (5.1%) patients had LVH. The mean CIMT in patients with LVH was 1.07 ± 0.24 mm and in those without LVH was 0.8 ± 0.11 mm. This showed that there was a significant increase in the mean carotid intimal thickness in patients with LVH. The P value for the same was <0.001 which is highly significant. Previous studies conducted by Cuspidi et al.,[21] Di Bello et al.,[22] Vaudo et al.[23] also observed a positive association between LVMI and increased CIMT.

CONCLUSIONS

Increased CIMT and LVH had a significant association with increased age, stage, and duration of hypertension, and presence of plaques. CIMT shows a significant increase in patients with LVH with P < 0.001. There is no significant correlation between BMI, LDL, and TC levels in patients with increased CIMT.

Limitation of the study

A relatively small sample size has limited the evaluation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.