Hypertension and Diabetes Mellitus: How Do They Affect the Right Ventricular Functions Individually and Together?

CONTEXT: The right ventricle (RV) is neglected in clinical practice although the RV function is the primary determinant of prognosis and effort tolerance in many groups of patients. AIM: The effects of type two diabetes mellitus and hypertension solitary and together were studied on right ventricular systolic and diastolic function by echo-Doppler and tissue Doppler echocardiography. SETTINGS AND
DESIGN: A cohort of 300 consecutive patients with echocardiographic right ventricular (RV) diastolic dysfunction as determined by Doppler echocardiography were included in this study. METHODS AND MATERIAL: Patients were divided in four groups, patients who were neither diabetic nor hypertensive, hypertensive patients, diabetic patients and those patients suffering from both hypertension and diabetes mellitus. Parameters of right ventricular systolic and diastolic function were compared. STATISTICAL ANALYSIS USED: Analyses were performed with SPSS version 12.0 statistical package (SPSS Inc., Chicago, IL, USA).
RESULTS: There was significant statistical difference between the four groups as regards E wave, E/A ratio and deceleration time measured by Doppler echocardiography. By pulsed wave tissue Doppler, S, E' and E/E' showed significant statistical difference between the four groups. All of these parameters were significantly different between the group suffering from both diseases and the group who had neither of them.
CONCLUSIONS: The combined effect of both, diabetes mellitus and hypertension on right ventricular function is stronger than the effect of one of them alone.

INTRODUCTION

Many studies were performed on the effect of hypertension (HTN) on the right ventricular (RV) systolic and diastolic functions.[12] Risk stratification of symptomatic heart failure can be achieved by assessing RV systolic and diastolic functions.[3] RV function plays a pivotal role in the coarse of heart failure,[4] atrial fibrillation,[5] ventricular arrhythmias, and sudden death.[6] However, only limited information is present on RV diastolic function in diabetic patients. Diabetic patients suffer from multiple causes of death; the most common is cardiovascular disease. Consequences of heart failure are more severe in diabetic patients than nondiabetics.[7]

For a long time, right ventricle remained underestimated and was assumed to be mainly a conduit, ignoring the hemodynamic importance of its contractile performance. The importance of the right ventricle in keeping normal cardiac physiology in many cardiovascular disorders has been recognized since the early 1950s. An increase in diastolic RV and right atrial pressures occurs as a result of RV dysfunction which impairs RV filling. As a consequence of this fluid retention, congestive hepatopathy occurs and cardiac cirrhosis can take place in more advanced cases. Significant tricuspid regurge which may occur due to RV failure may increase RV overload and decrease cardiac output.[8]

The aim of this study was to determine the effects of the presence of diabetes mellitus (DM) superadded on HTN on RV functions assessed by conventional echo-Doppler and tissue Doppler echocardiography and to compare the effects of the each of the individual diseases with the combination and absence of both HTN and DM on RV functions.

PATIENTS AND METHODS

Patients selection

A cohort of 300 consecutive patients with echocardiographic RV diastolic dysfunction (DD)[9] was included throughout the period from January 2015 to January 2016. To be eligible, patients needed to be in sinus rhythm. We excluded patients with significant valvular or congenital heart disease, congestive heart failure, cardiomyopathy, left ventricular systolic dysfunction (defined by an ejection fraction (EF) <40%), ischemic heart disease, advanced lung disease, pulmonary HTN, bundle branch block, pericarditis, and those receiving antiarrhythmic drugs or suffering from Type I DM.

Before inclusion, informed written consent was obtained from each patient after full explanation of the study protocol, and the protocol was reviewed and approved by our Institutional Human Research Committee as it conforms to the ethical guidelines of 1975, the Declaration of Helsinki, as revised in 2013.

Four groups were compared, patients who were neither diabetic nor hypertensive, hypertensive patients, diabetic patients, and those patients suffering from both HTN and DM as regards parameters of RV function.

Definition of risk factors

The presence of HTN was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, previously recorded by repeated noninvasive office measurements, which lead to life-style modification or antihypertensive drug therapy.[10] DM was defined according to the diagnostic criteria described by the American Diabetes Association as fasting plasma glucose ≥126 mg/dl, and/or 2-h postload glucose ≥200 mg/dl, or specific antidiabetic drug therapy.[1112]

Echocardiography

This was performed to all subjects according to the same protocol with the use of GE Medical system Vivid 7 ultrasound machine equipped with 2–4 MHz sector transducer probe. Routine echocardiography with the standard projections was done initially and followed by Doppler flow tracing registration at the level of mitral and tricuspid valves. All echo-Doppler measurements were analyzed by the average of three cardiac cycles, to minimize difference during the breath cycles.

Parameters obtained through parasternal approaches in the M-mode projection were analyzed: left ventricular end diastolic diameter, left ventricular end systolic diameter, interventricular septum, left ventricular posterior wall (PW) thickness, aortic root dimension, and left atrial diameter.

The assessment of the left ventricular systolic function consisted of fraction shortening %, left ventricular EF% obtained according to Simpson's formula.[13]

RV global systolic function was assessed as tricuspid annular plane systolic excursion (TAPSE), by two-dimensional difference of end-diastolic and end-systolic lines (in mm) traced between the center of the ultrasound fan origin and the junction of RV lateral tricuspid annulus, in apical four-chamber view.[1415] The following measurements of RV global filling were determined: E and A peak velocities (m/s), E/A ratio, and E wave deceleration time.[16]

Tricuspid annular velocity by Doppler tissue imaging

We used the same GE Vivid Seven machine using a commercially available imaging system equipped with a 2–4 MHz transducer and secondary harmonic imaging to optimize endocardial border visualization. The spectral pulsed Doppler signal filters were adjusted until a Nyquist limit of 15–20 cm/s and the minimal optimal gain was used. From the apical four chamber view, the longitudinal tricuspid annular velocities were recorded from lateral RV site using PW-Doppler tissue imaging. The values from the above site were used to assess global systolic and diastolic function. Three major velocities were taken into account: The positive peak systolic velocity when the tricuspid ring moved toward the cardiac apex due to longitudinal contraction of the RV (S) and two negative diastolic velocities when the tricuspid annulus moved toward the base away from the apex, one during the early phase of diastole (E’) and the other in the late phase of diastole (A’). A mean of three consecutive cycles was used to calculate all echo-Doppler parameters. RV DD was graded according to tricuspid E/A ratio, E/E’, and deceleration time.[9]

Statistical analysis

Data are presented as mean ± standard deviation. The Chi-square test was used to compare differences between proportions. The analysis of variance test was used for the analysis of continuous data. Post hoc test was performed for comparison between each two of the four variables. A probability value of P < 0.05 was considered statistically significant. Analyses were performed with SPSS version 12.0 statistical package (SPSS Inc., Chicago, IL, USA). Differences were considered significant if the null hypothesis could be rejected at the. 05 probability level.

RESULTS

Baseline clinical characteristics

The mean age of the whole cohort was 56.03 ± 10.04 years; 50.7% were male. Both systolic and diastolic blood pressure were measured, 36.7% of the studied patients were hypertensive, and 35.3% were diabetic. The other baseline clinical characteristics are shown in Tables 1 and 2.

Table 1

Frequency distribution of the studied patients according to their demographic characteristics

Patient demographic characteristics	n (%)
Gender
Male	152 (50.7)
Female	148 (49.3)
HTN
No	190 (63.3)
Yes	110 (36.7)
Diabetes
No	194 (64.7)
Yes	106 (35.3)
Smoking
No	160 (53.3)
Yes	140 (46.7)
Total	300 (100.0)

HTN=Hypertension

Table 2

Descriptive statistics of patient characteristics

Patient characteristics	Minimum	Maximum	Mean±SD
Age (years)	40.00	85.00	56.0315±10.03546
HT (cm)	150.00	190.00	166.3583±8.94613
WT (kg)	55.00	130.00	86.8504±12.97372
BMI (kg/cm2)	18.50	44.90	31.6044±5.15820
SBP (mmHg)	100.00	180.00	140.2362±20.20995
DBP (mmHg)	60.00	110.00	87.0079±11.17167
Pulse (bpm)	60.00	100.00	76.4764±7.47152

HT=Height, WT=Weight, BMI=Body mass index, SBP=Systolic blood pressure, DBP=Diastolic blood pressure, SD=Standard deviation

Echocardiographic data

Echocardiographic data of the left ventricular assessment are shown in Table 3. Left ventricular dimensions and thickness were measured. EF was calculated. Table 4 shows RV diastolic function parameters assessed by Doppler and pulsed-wave tissue Doppler. Four groups were compared, patients who were neither diabetic or hypertensive, hypertensive patients, diabetic patients and those patients suffering from both HTN and DM. There was significant statistical difference between the four groups as regards E wave, E/A ratio, and deceleration time measured by Doppler echocardiography. By pulsed-wave tissue Doppler, S, E’, and E/E’ showed significant statistical difference between the four groups.

Table 3

Descriptive statistics of the left ventricular functions

LV functions	Minimum	Maximum	Mean±SD
LVEDD (cm)	3.30	5.70	4.8425±0.54083
LVESD (cm)	2.00	4.00	3.0894±0.41933
PWT (cm)	0.60	1.50	1.0394±0.16641
Sept (cm)	0.60	1.50	1.0882±0.19321
FS (%)	26.00	49.00	34.8268±4.77078
EF (%)	50.00	80.00	65.3622±6.09434
LA (cm)	2.50	5.10	3.8665±0.53769
AO root (cm)	2.10	4.50	3.1764±0.45544

LVEDD=Left ventricular end diastolic diameter, LVESD=Left ventricular end systolic diameter, PWT=Posterior wall thickness, Sept=Interventricular septum, FS=Fractional shortening, EF=Ejection fraction, LA=Left atrium, AO=Aortic, SD=Standard deviation

Table 4

Comparison between the four studied groups as regards right ventricular function by conventional echo-Doppler echocardiography and pulsed-wave tissue Doppler by the analysis of variance test

Parameter	Negative	HTN	Diabetes	Both	P
E (cm/s)	47.82±10.61	51.42±13.55	45.14±9.47	62.61±14.83	0.000
A (cm/s)	54.33±16.48	58.71±14.59	54.29±11.71	61.16±15.24	0.039
E/A	0.92±0.24	0.91±0.26	0.86±0.20	1.08±0.35	0.001
DT (m)	214.81±53.23	223.84±71.56	239.00±76.20	186.19±8.99	0.002
TAPSE (mm)	2.47±0.32	2.57±0.33	2.61±0.34	2.58±0.35	0.113
S (cm/s)	15.02±5.25	12.71±4.51	12.90±3.74	11.47±4.49	0.000
E’ (cm/s)	12.46±3.39	10.98±3.41	11.33±2.39	9.25±1.96	0.000
A’ (cm/s)	13.89±3.28	13.08±3.90	13.90±3.16	12.25±4.15	0.058
E/E’	4.06±1.20	5.05±1.85	4.27±1.70	7.04±1.99	0.000
E’/A’	0.93±0.29	0.90±0.30	0.83±0.18	0.81±0.23	0.051

Negative=Patients who are not suffering from HTN or DM, Both=Patients who are suffering from both HTN and DM, E=Peak velocity of the early E-wave, A=Peak velocity of late A-wave, E/A=E/A ratio, DT=Deceleration time of the early diastolic flow, TAPSE=Tricuspid annular plane systolic excursion, S=Positive peak systolic velocity measured by Doppler tissue imaging at tricuspid valve annulus, É=Early diastolic negative velocity measured by Doppler tissue imaging at tricuspid valve annulus, Á=Late diastolic negative diastolic velocity measured by Doppler tissue imaging at tricuspid valve annulus, HTN=Hypertension, DM=Diabetes mellitus

Table 5 shows post hoc test to detect the exact site of significance; it was found that the most powerful effect on RV function was by the combined effect of DM and HTN. HTN effects were clear by tissue Doppler imaging. When post hoc test was performed to the parameters which showed nonsignificant statistical difference between the four studied groups, A’ and E’/A’ showed significant statistical difference only between the group who had neither DM nor HTN and those who suffer from both diseases.

Table 5

Comparison between the four studied groups as regards right ventricular function by conventional echo-Doppler echocardiography and pulsed-wave tissue Doppler by post hoc test (P value)

Parameter	Negative versus HTN	Negative versus DM	Negative versus both	HTN versus DM	HTN versus both	DM versus both
E (cm/s)	0.061	0.386	0.000	0.042	0.000	0.000
A (cm/s)	0.057	0.991	0.009	0.230	0.342	0.078
E/A	0.666	0.291	0.001	0.427	0.000	0.002
DT (m)	0.362	0.131	0.011	0.340	0.001	0.002
TAPSE (mm)	0.053	0.093	0.056	0.627	0.829	0.750
S (cm/s)	0.001	0.066	0.000	0.868	0.120	0.235
E’ (cm/s)	0.002	0.132	0.000	0.632	0.001	0.008
A’ (cm/s)	0.146	0.991	0.010	0.358	0.186	0.081
E/E’	0.000	0.616	0.000	0.057	0.000	0.000
E’/A’	0.324	0.161	0.008	0.425	0.066	0.645

Negative=Patients who are not suffering from HTN or DM, Both=Patients who are suffering from both HTN and DM, E=Peak velocity of the early E-wave, A=Peak velocity of late A-wave, E/A=E/A ratio, DT=Deceleration time of the early diastolic flow, TAPSE=Tricuspid annular plane systolic excursion, S=Positive peak systolic velocity measured by Doppler tissue imaging at tricuspid valve annulus, É=Early diastolic negative velocity measured by Doppler tissue imaging at tricuspid valve annulus, Á=Late diastolic negative diastolic velocity measured by Doppler tissue imaging at tricuspid valve annulus, HTN=Hypertension, DM=Diabetes mellitus

DISCUSSION

This study describes the effect of DM and HTN individually and together on RV function assessed by both conventional echocardiography and pulsed-wave tissue Doppler echocardiography. The parameters used to assess systolic function of the RV were TAPSE[1415] and S wave of pulsed-wave tissue Doppler while all diastolic parameters of tricuspid valve Doppler were measured relying mainly on E/A ratio, E/E’ and deceleration time.[9]

Cardiac morbidity and mortality in numerous diseases can be predicted by RV dysfunction as one of the powerful items to be considered. This has been found in heart failure with preserved function[17] and ST-segment elevation myocardial infarction.[181920] One of the main findings of this study was that there was significant statistical difference between the studied groups regarding the RV systolic function as indicated by S wave velocity measured by pulsed-wave tissue Doppler while TAPSE showed no difference between the four studied group.

In concordance with the results of this study, the previous studies showed that TAPSE which is a good parameter for systolic RV systolic function was not affected in hypertensive patients.[2] The longitudinal displacement of the tricuspid annulus can be measured by TAPSE and S’ by two different methods. S’ is correlated to RV EF estimated by magnetic resonance imaging than TAPSE.[21] The ability of tissue Doppler echocardiography to detect abnormalities in a specific region of interest in the myocardium while the rest of the chamber is normal has been illustrated by the previous studies.[22]

Regarding the diastolic function, the significant statistical difference between the four studied groups was present in E and A wave velocities and E/A ratio estimated by Doppler echocardiography. Comparing the parameters of pulsed-wave tissue Doppler S wave, E’ wave, and E/E’ showed significant statistical difference between the hypertensives, diabetics, those suffering from both disease (both) and those not suffering from any of them (negative).

RV diastolic function measured by pulsed-wave tissue Doppler has been proven to be affected hypertensive patients[2] which agrees with this study. In another study, they also found that RV DD could be the earliest index of RV affectation in HTN.[23] The previous studies have studied the effect of HTN in nonobese and never-treated patients on the right ventricle. They found deterioration in systolic and diastolic functions of the right ventricle even in slightly increased blood pressure.[24]

The effects of antihypertensive drugs on the diastolic function of the left ventricle and pulmonary artery pressure had been studied by several authors. Prevention of smooth muscle proliferation and vascular remodeling together with the improvement of endothelial dysfunction are among neurohumoral inhibitory actions of angiotensin converting enzymes and angiotensin receptor blockers. This occurs in addition to their action as effective vasodilators. These are some of the modes of antihypertensive drugs.[2526] In our study, the patients received several antihypertensive drugs 15% of the hypertensive patients received angiotensin receptor blockers, 18% of them received angiotensin converting enzymes inhibitors and 14% of them received calcium channel blockers (data not shown). The effects of these drugs were not studied, but this point needs further studies.

The results showed that the difference between all the studied items of systolic and diastolic functions of the right ventricle was statistically significant between the two groups, those who suffered from both DM together with HTN and those who were free from both diseases.

Unlike previous studies, DM alone did not show effects on the RV function. This can be explained by the fact that previous studies focused on the inclusion of those who suffer from diabetic cardiovascular complications when they studied the effect of diabetes on RV diastolic function or inclusion of type one DM.

The present study has some limitations. Patients suffering from Type I DM were not included in the study, and hypertensive patients were not divided into grades. The results were not validated against MRI, which is regarded as the gold standard for RV function assessment. The effect of both diseases with their various types is variable and needs further studies on a larger scale.

CONCLUSION

RV function is affected by HTN which was evident by tissue Doppler imaging. The combined effect of both, DM and HTN on RV function is more evident in all parameters than the effect of one of them alone.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.