_08_KP_7_8_2021__Goracy
  • „ ORIGINAL ARTICLE

Key genetic variants in the renin-angiotensin system and left ventricular mass in a cohort of Polish patients with heart failure

Iwona Gorący1, Małgorzata Peregud-Pogorzelska2, Krzysztof Safranow3, Andrzej Ciechanowicz1

1Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland

2Clinic of Cardiology, Pomeranian Medical University, Szczecin, Poland

3Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland

Editorial

by Palmer,

see p. 728

Correspondence to:

Iwona Gorący, MD,

Department of Clinical and Molecular Biochemistry,

Pomeranian Medical University,

Powstańców Wlkp. 72, 70–111 Szczecin, Poland,

phone: +48 91 4661490,

e-mail: igor@pum.edu.pl

Copyright by the Author(s), 2021

Kardiol Pol. 2021; 79 (7–8): 765–772; DOI: 10.33963/KP.15989

Received: February 25, 2021

Revision accepted: April 26, 2021

Published online: April 29, 2021

 

ABSTRACT

Background: Heart failure (HF) is a complex disease that is under the control of different physiological systems. Left ventricular mass (LVM) is a strong predictor of HF. The renin-angiotensin system (RAS) may contribute to the pathogenesis of HF and LVM.

Aims: The aim of this study is to examine the association between RAS genetic variants and HF and LVM in the cohort of Polish patients with HF.

Methods: The study included 401 patients with HF. Two-dimensional M-mode echocardiography was used to assess LVM. Genomic DNA was extracted from blood, and genotyping of the angiotensin-converting enzyme (ACE) (rs4646994), angiotensinogen (AGT) (rs5051), and angiotensin II receptor type 1 (AGTR1) (rs5186) polymorphisms was carried out using polymerase chain reaction (PCR).

Results: A significant association was found between HF and the genotypes of G(–6)A AGT, and the homozygotes AA of AGT were significantly less common in the HF vs control group. The results of this study did not confirm the relationship between AGT, ACE and AT1R genetic variants with LVM in Polish patients with HF.

Conclusions: Our results suggested that AGT polymorphism may play a protective role in the development of HF.

Key words: genes, heart failure, left ventricular mass, renin-angiotensin system

Kardiol Pol 2021; 79, 78: 765772

WHAT’S NEW?

Heart failure (HF) is a major cause of morbidity and mortality in the world. The renin-angiotensin system (RAS) plays an important role in the pathophysiology of HF development and left ventricular dysfunction. Left ventricular mass (LVM) is a major contributor to the development of heart failure. The search for genetic variants that could act as prognostic markers that could be used to predict poor outcomes and assist in selecting appropriate therapy is still ongoing. To determine the relationship between the key RAS genetic variants: G(–6)A angiotensinogen (AGT), insertion/deletion polymorphism of angiotensin-converting enzyme (I/D ACE) or A1166C angiotensin II receptor type 1 (AGTR1), and HF or LVM, we studied 401 Polish patients with HF. Our results suggested that AGT polymorphism may play a protective role in the development of HF.

INTRODUCTION

Heart failure (HF) is a growing global health problem that is also responsible for high mortality. The most common causes of HF are ischemic heart disease (IHD), hypertension (HT), valvular heart disease (VD) or cardiomyopathy [1]. However, it is known that the etiology of HF is complex and researchers are still looking for factors that influence the development and progression of HF.

It is already known that the renin-angiotensin system (RAS) plays an important role in the pathophysiology of left ventricular (LV) dysfunction, left ventricular hypertrophy (LVH), regulation of arterial pressure, cardiovascular diseases, and thus, HF [2]. Angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin II receptor type 1 (AGTR1) are key components of RAS. So far, researchers have shown that AGT polymorphisms are mainly associated with the development of HT or IH [3, 4], while the correlations with HF remain inconsistent [5, 6]. However, some studies indicate a correlation between AGT gene polymorphism and increased left ventricular mass (LVM) [7, 8], and LVH is a strong predictor of HF [9].

The insertion/deletion polymorphism (I/D) of the ACE gene is the most extensively studied and has been shown to be correlated with HT, IHD and other cardiovascular intermediate phenotypes [1015]. Moreover, ACE has been known to have a crucial role in the development of cardiac remodeling by either angiotensin II or aldosterone [16]. There are some reports that suggest that this polymorphism is associated with increased LVM in normotensive and hypertensive patients or in patients with cardiomyopathy [17, 18], although there are studies that do not support this correlation [19, 20]. While the genetic determinants of LVM in patients with HF have not been so extensively studied, the role of the I/D ACE polymorphism in shaping LVM is not fully understood. There is no direct reporting targeting of genetic predisposition to increase LVM in patients with HF, and the role of I/D ACE polymorphism in LVM modulation may be significant, and thus, for HF may be of pivotal importance.

The effect of AGTR1 on the regulation of LVM was also demonstrated, as it was found to influence the regulation of blood volume and stimulate the growth and proliferation of heart cells, which causes the development of HF [21]. However, the results of available studies remain controversial and other studies were not able to detect any influence of RAS gene polymorphisms on LVM [22, 23]. Although the potential role of the RAS system in structure and heart disorders is relatively well understood, these molecular mechanisms involved in LVM in patients with HF continue to be studied. Especially, RAS genetic polymorphisms involved in HF pathophysiology are of particular interest as the plausible candidates may play a role in modifying LVM.

Therefore, the aim of our study was to analyze the association between the G(–6)A AGT (rs5051), I/D ACE (rs4646994) and A1166C AGTR1 (rs5186) genetic variants and both HF and the LVM in a cohort of Polish patients with HF.

METHODS

Patients

This study was conducted in accordance with the Declaration of Helsinki and was approved by the local bioethics committee at the Pomeranian Medical University (PMU) in Szczecin, Poland. Written informed consent was obtained from study participants.

This was a case-control study of patients with a diagnosis of HF from Department of Cardiac Surgery and Cardiology Department of PMU. A total of 401 patients (293 men, 108 women) included in the study had symptomatic HF, defined as New York Heart Association (NYHA) functional class IIV. The study group with HF included patients with IHD (n = 245; 192 men, 53 women), patients with VD (n = 68; 37 men, 31 women), and patients with combined disease, IHD and VD (n = 88; 64 men, 24 women). Among these HF patients were 195 patients with reduced ejection fraction <50% (HF with reduced ejection fraction [HfrEF] subgroup). Doppler echocardiography was used to examine LV dysfunction.

Demographic data and medical history of patients were collected from their medical chart records. The control group was consisted of 120 volunteers (43 men, 77 women) without history of cardiac disease.

Echocardiography

Transthoracic echocardiography was performed using an Acuson Sequoia 512 unit (Siemens, Munich, Germany) equipped with a 24 MHz imaging transducer, according to the recommendations of the American Society of Echocardiography (ASE). Measurements of LV end-diastolic diameter (LVEDD), LV septal wall thickness diameter (IVTd) and posterior wall thickness diameter (PWTd) were obtained in the M-mode parasternal long-axis view. An average of values after three image acquisitions was calculated. In cases with suboptimal M-mode acquisition, measurements in two-dimensional views were obtained instead. LVM was calculated with the ASE-recommended formula [24]: LVM (g) = 0.8 × {1.04 [(LVEDD + PWTd + IVTd)3 – (LVEDD)3]} + 0.6 g. Body surface area was calculated using the Mosteller formula {square root [height (cm) × weight (kg)]/3600} and LVM was indexed to the body surface area. LVH was defined as LV mass index (LVMI) >115 g/m2 in men and >95 g/m2 in women [24].

Genotyping

Genomic DNA was isolated from whole blood collected into ethylenediaminetetraacetic acid tubes using the QIAamp Blood DNA Mini Kit (QIAGEN, Hilden, Germany).

For the analysis, a polymerase chain reaction and polymerase chain reaction/restriction fragments length polymorphism (PCR/RFLP) method were applied. Genotyping of the G(–6)A AGT (rs5051), I/D ACE (rs4646994) and A1166C AGTR1 (rs5186) polymorphisms were carried out as previously described [25].

Statistical analysis

The distributions of all quantitative variables, except age, were significantly different from normal distribution (P <0.05, Shapiro-Wilk’s test). Therefore, quantitative variables were presented as the median with lower quartile and upper quartile, and analyzed using the non-parametric Kruskal-Wallis or the Mann-Whitney U test. Qualitative variables were presented as number with corresponding percentage and compared between groups with the chi-square or the Fisher exact test. Concordance of genotype distribution with Hardy-Weinberg equilibrium was performed with the exact test. Strength of association of qualitative variables with genotypes and alleles was described as odds ratio (OR) with 95% confidence interval (95% CI). Multivariable logistic regression analysis adjusted for age and sex was performed to verify whether the associations of genetic polymorphisms with HF are independent of these demographic factors. P <0.05 was considered statistically significant without correction for multiple tests. Bonferroni-corrected P-value thresholds were calculated as follows: for the study of associations between HF and each of the 3 polymorphisms in 4 models of inheritance (dominant, recessive or additive mode for minor allele as well as comparison of wild-type homozygotes with mutated ones), 3 × 4 = 12 tests were performed, so the corrected P-value threshold was 0.05/12 = 0.0042; for the study of associations between LVMI and each of the 3 polymorphisms in 4 aforementioned models of inheritance in the whole group of HF patients and in the subgroups with arterial hypertension or with HFrEF, 3 × 4 × 3 = 36 tests were performed, so the corrected P-value threshold was 0.05/36 = 0.0014. Calculations were performed with Statistica 13 software (Statistica, Dell Inc. [2016], version 13, software.dell.com).

RESULTS

The baseline characteristics of the HF subjects is shown in Table 1. T

Table 1. Clinical and echocardiographic characteristics of patients with HF and control group

Characteristics

HF cases (n = 401)

Control (n = 120)

P-valuea

Age, years

66.0 (61.0–71.0)

56.0 (49.0–63.0)

<0.0001

BMI, kg/m2

29.0 (25.8–31.7)

27.3 (24.8–29.4)

<0.0001

Males

293 (73)

77 (64)

0.077

Smoking

126 (31)

24 (20)

0.021

Diabetes mellitus

258 (64)

9 (7)

<0.0001

Hypertension

337 (84)

24 (20)

<0.0001

Echocardiographic parameters

 

 

IVT, cm

1.25 (1.10–1.40)

0.97 (0.95–1.00)

<0.0001

PWT, cm

1.10 (1.00–1.25)

1.05 (1.00–1.10)

<0.0001

LVEDD, cm

5.00 (4.61–5.50)

4.75 (4.31–5.05)

<0.0001

EF, %

50.0 (40.0–55.0)

64.0 (62.0–67.2)

<0.0001

LVM, g

241.8 (195.9–293.8)

171.5 (147.9–190.3)

<0.0001

LVMI, g/m2

125.7 (99.3–149.5)

88.8 (76.0–102.5)

<0.0001

Quantitative variables are presented as median (IQR) and qualitative data are presented as a number with corresponding percentage.

aThe Fisher exact test for qualitative variables and the Mann-Whitney U test for quantitative variables.

Abbreviations: BMI, body mass index; EF, ejection fraction; HF, heart failure; IVT, left ventricular septal wall thickness; LVEDD, left ventricular end-diastolic diameter; LVM, left ventricular mass; LVMI, left ventricular mass index; PWT, posterior wall thickness

he BMI and age proved to be significantly higher in the HF group, when compared to controls. Similarly, smoking, diabetes, and HT were more common among HF patients than controls. Significant differences in all echocardiographic parameters were noted between HF patients and controls (higher IVT, PWT, LVM, LVMI, LVEDD and lower ejection fraction [EF] values in the HF group) (Table 1).

The G(–6)A AGT, I/D ACE and A1166C AGT1R gene polymorphism genotypes were found to be in Hardy-Weinberg equilibrium both in the HF and control group (P >0.1). We observed a significant association between HF and genotypes of G(–6)A AGT (Table 2).

Table 2. Genotype frequencies for G(–6)A AGT, I/D ACE, A1166C AGT1R in patients with HF and control group

Polymorphism

HF group

(n = 401)

Control group

(n = 120)

P-valuea

Compared genotypes or alleles

OR (95% CI)

P-valueb

AGT genotype

 

GG

108

26.9%

31

25.8%

0.042

AA + GA vs GG

0.945 (0.594–1.504)

0.811

GA

215

53.6%

53

44.2%

AA vs GA + GG

0.564 (0.355–0.895)

0.014c

AA

78

19.6%

36

30.0%

AA vs GG

0.622 (0.355–1.091)

0.096

AGT allele

 

G

431

53.7%

115

47.9%

A vs G

0.792 (0.593–1.057)

0.113

A

371

46.3%

125

52.1%

ACE genotype

 

II

92

22.9%

27

22.5%

0.99

DD + ID vs II

0.975 (0.599–1.588)

0.919

ID

207

51.6%

62

51.7%

DD vs ID + II

0.979 (0.614–1.562)

0.930

DD

77

25.5%

31

25.8%

DD vs II

0.966 (0.536–1.738)

0.907

ACE allele

 

I

391

48.8%

116

48.3%

 

D vs I

0.983 (0.737–1.312)

0.909

D

411

51.2%

124

51.7%

AGTR1 genotype

 

AA

219

54.6%

61

50.8%

0.73

CC + AC vs AA

0.859 (0.571–1.293)

0.466

AC

154

38.4%

49

40.8%

CC vs AC + AA

0.826 (0.389–1.753)

0.618

CC

28

7.0%

10

8.4%

CC vs AA

0.780 (0.359–1.694)

0.529

AGTR1 allele

 

A

592

73.8%

171

71.3%

C vs A

0.879 (0.638–1.212)

0.431

C

210

26.2%

69

28.8%

aThe Chi-square test for difference in frequencies of 3 genotypes. bThe Chi-square test for difference in frequencies of 2 genotypes, genotype groups or alleles. cOR, 0.427; 95%CI, 0.245–0.742; P = 0.0025 in multivariable logistic regression model adjusted for age and sex.

Abbreviations: ACE, angiotensin-converting enzyme; AGT, angiotensinogen; AGTR1, angiotensin II receptor type 1; CI, confidence interval; HF, heart failure; I/D, insertion/deletion; OR, odds ratio

Analyses revealed that homozygotes AA of AGT are significantly less common in the HF group than in the control group (P = 0.014). The negative association between AA AGT genotype and HF was even stronger in multivariable logistic regression model adjusted for age and sex (OR, 0.427; 95% CI, 0.2450.742; P = 0.0025), reaching the Bonferroni-corrected P-value threshold (<0.0042). No association was found between I/D ACE or A1166C AGT1R gene polymorphism and HF, both in univariable and multivariable analyses (P >0.3).

The results of association of the G(–6)A AGT, I/D ACE and A1166C AGT1R polymorphisms with LVMI in HF patients are summarized in Table 3.

Table 3. Association of G(–6)A AGT, I/D ACE, A1166C AGTR1 genotypes and LVMI in HF patients (n = 401)

Polymorphism

LVMI, g/m2

P-valuea

Compared genotypes

P-valueb

AGT genotype

 

GG

126.2 (94.6–153.6)

0.268

AA + GA vs GG

0.953

GA

121.3 (98.3–146.1)

AA vs GA + GG

0.126

AA

132.8 (103.2–152.9)

AA vs GG

0.315

ACE genotype

 

II

126.1 (99.3–150.0)

0.290

DD + ID vs II

0.689

ID

126.1 (101.5–152.8)

DD vs ID + II

0.116

DD

118.8 (96.2–141.0)

DD vs II

0.233

AGTR1 genotype

 

AA

121.4 (100.7–145.4)

0.241

CC + AC vs AA

0.284

AC

132.5 (99.8–155.6)

CC vs AC + AA

0.357

CC

116.9 (88.0–142.8)

CC vs AA

0.516

LVMI is presented as median (IQR).

aThe Kruskal-Wallis test. bThe Mann-Whitney U test.

Abbreviations: see Table 1 and Table 2

We did not detect any significant correlations. The results of these tests on the effects of G(–6)A AGT, I/D ACE and A1166C AGT1R polymorphisms with LVH defined as LVMI >115 g/m2 in men and >95 g/m2 in women are presented in Table 4.

Table 4. Association of G(–6)A AGT, I/D ACE, A1166C AGTR1 genotypes and LVH in HF patient group (n = 401)

Polymorphism

Patients with LVH

(n = 262)

Patients without LVH

(n = 139)

P-valuea

Compared genotypes or alleles

OR (95% CI)

P-valueb

AGT genotype

GG

71

27.1%

37

26.6%

0.23

AA + GA vs GG

0.976 (0.613–1.553)

0.918

GA

134

51.6 %

81

58.3%

AA vs GA + GG

1.562 (0.902–2.706)

0.109

AA

57

21.8 %

21

15.1%

AA vs GG

1.414 (0.747–2.680)

0.287

AGT allele

G

276

52.7%

155

55.8%

A vs G

1.132 (0.845–1.517)

0.405

A

248

47.3%

123

44.2%

ACE genotype

II

62

23.7%

30

21.6%

0.28

DD + ID vs II

0.888 (0.542–1.456)

0.637

ID

140

53.5%

67

48.2%

DD vs ID + II

0.686 (0.432–1.090)

0.109

DD

60

22.9%

42

30.2%

DD vs II

0.828 (0.619–1.109)

0.205

ACE allele

I

264

50.4%

127

45.7%

D vs I

0.828 (0.619–1.109)

0.205

D

260

49.6%

151

54.3%

AGTR1 genotype

AA

139

53.1%

80

57.6%

0.49

CC + AC vs AA

1.200 (0.793–1.817)

0.389

AC

106

40.5%

48

34.5%

CC vs AC + AA

0.807 (0.367–1.775)

0.594

CC

17

6.5%

11

7.9%

CC vs AA

0.890 (0.397–1.993)

0.776

AGTR1 allele

A

384

73.2%

70

25.2%

C vs A

1.083 (0.777–1.511)

0.637

C

140

26.7%

208

74.82%

aThe Chi-square test for difference in frequencies of three genotypes. bThe Chi-square test for difference in frequencies of two genotypes, genotype groups or alleles.

Abbreviations: see Table 1 and Table 2

We did not find any significant correlations.

We also found no relationship between the studied polymorphisms and LVMI in the subgroup of patients with HF and arterial hypertension (n = 309; P >0.1; data not shown).

Subsequently, we conducted an analysis of the effect of G(–6)A AGT, I/D ACE and A1166C AGT1R genotypes on LVH in a subgroup of HF patients with HFrEF <50% (Table 5). The presence of the DD ACE genotype was significantly associated with a lower prevalence of LVH in patients with HFrEF (OR, 0.450 [95%CI 0.2260.895]; P = 0.021). However, this association did not reach Bonferroni-corrected P-value threshold (<0.0014).

Table 5. Association of G(–6)A AGT, I/D ACE, A1166C AGTR1 genotypes and LVH in HF patients with reduced ejection fraction (n = 195)

Polymorphism

HFrEF patients with LVH (n = 138)

HFrEF patients without LVH (n = 57)

P-valuea

Compared genotypes or alleles

OR (95% CI)

P-valueb

AGT genotype

 

GG

36

26.1%

13

22.8%

0.889

AA + GA vs GG

0.837 (0.405–1.730)

0.631

GA

77

55.8%

33

57.9%

AA vs GA + GG

0.925 (0.421–2.034)

0.847

AA

25

18.1%

11

19.3%

AA vs GG

0.821 (0.317–2.125)

0.684

AGT allele

 

G

149

54.0%

59

51.8%

A vs G

0.914 (0.591–1.416)

0.688

A

127

46.0%

55

48.3%

ACE genotype

 

II

38

27.5%

11

19.3%

0.063

DD + ID vs II

0.629 (0.295–1.341)

0.228

ID

73

52.9%

26

45.6%

DD vs ID + II

0.450 (0.226–0.895)

0.021

DD

27

19.6%

20

35.1%

DD vs II

0.391 (0.161–0.948)

0.035

ACE allele

 

I

149

54.0%

48

42.1%

D vs I

0.620 (0.399–0.963)

0.033

D

127

46.0%

66

57.9%

AGTR1 genotype

 

AA

72

52.2%

33

57.9%

0.632

CC + AC vs AA

1.260 (0.676–2.350)

0.466

AC

54

39.1%

21

36.8%

CC vs AC + AA

1.714 (0.465–6.320)

0.413

CC

12

8.7%

3

5.3%

CC vs AA

1.833 (0.486–9.360)

0.366

AGTR1 allele

 

A

198

71.7%

87

76.3%

C vs A

1.269 (0.766–2.103)

0.354

C

78

28.3%

27

23.7%

aThe Chi-square test for difference in frequencies of three genotypes. bThe Chi-square test for difference in frequencies of two genotypes, genotype groups or alleles.

Abbreviations: HFrEF, HF patients with reduced ejection fraction; LVH, left ventricular hypertrophy; other, see Table 1 and Table 2

 

DISCUSSION

This study evaluated the role of the G(–6)A AGT, I/D ACE and A1166C AGTR1 polymorphisms with HF and LVM in patients with HF. Although the association between the RAS polymorphisms and cardiovascular disease has been demonstrated in many previous studies, this relationship is still controversial. The importance of RAS polymorphisms in relation to HF has not been fully explained and is still widely discussed, and reports on these issues are contradictory. To our knowledge, this is the first cohort study that examined the association of the key RAS gene polymorphisms and HF and LVM in Polish patients. The present study demonstrated a correlation between HF and the AA genotype of the AGT gene.

Excessive circulating and tissue angiotensin II and aldosterone levels have been shown to lead to a profibrotic, proinflammatory, and prohypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues [26]. Therefore, molecular variants of RAS are considered to be important for LVM, and thus, HF. To date, the relationship of M235T AGT polymorphism and HF was the most studied. It has been demonstrated that the concentration of AGT in blood increases with the number of T235 alleles [27]. Some studies demonstrate that this single nucleotide polymorphism (SNP) of AGT may be associated with HF in different populations [27, 28], whereas some studies did not find associations between M235T AGT and HF [7, 29]. In our study, we examined the association between the G(–6)A AGT polymorphism with HF, and this polymorphism remains in very tight linkage disequilibrium with T235 AGT and marks the original form of the gene. The functionality of (–6G) AGT variants was demonstrated by their influence on the basal transcription rate [30]. In this study, we found association between G(–6)A of AGT and HF in our population, the analysis revealed the protective role of the homozygotes AA for HF. Additionally, we noted the lack of association of the I/D ACE and A1166C AGTR1 polymorphisms. The obtained result of the correlation of (–6) AGT polymorphism with HF may result from the different concentration of AGT. Given the important role of AGT in regulating RAS, it is likely that the AGT polymorphism may modulate the risk of developing HF in the Polish population. However, these findings still need to be clarified.

The association between RAS polymorphisms and LVH has been demonstrated in numerous published studies [31, 32]. However, the relationship between these polymorphisms and LVM and HF is still not fully understood, and better understanding of the complexity of RAS should help modulate this system and consequently improve quality of life. As it is known, in the course of HF during pressure overload, there is myocardial remodeling, which leads to myocardial hypertrophy, as the result of adaptation to mechanical workload demands. However, under pathological conditions of the onset of HF, myocardial remodeling reactions often become maladjusted, leading to myocardial decompensation. This phenomenon is associated with increased wall stress, insufficient or inappropriate cardiomyocyte hyperplasia, apoptosis or increased fibrosis [26].

In our study, we did not demonstrate any relationship between the RAS genes studied and LVM.

This relatively weak influence of genetic factors on LVM in our patients with HF may be due to a strong influence of risk factors of HF. In the Polish population, traditional risk factors for cardiovascular diseases (e.g., obesity, HT, diabetes mellitus, smoking, etc.) are still widespread, and as presented by Favé at al. [33], local environment directly influences disease-risk phenotypes and genetic variation, including fewer common variants, and can also modulate individual responses to environmental challenges. Previously, we presented a study in which we showed that ACE, AT1R and MTHFR gene polymorphisms do not predispose to a greater LVM in Polish patients with myocardial infarction [34].

Furthermore, it should be noted that the patients in our program were treated for HF (mainly with ACE inhibitors, angiotensin receptor antagonists, calcium inhibitors, etc.), especially with drugs from the group of which RAS inhibitors may modulate LVM, which may have affected our results. It has been proven in numerous studies that the inhibition of the RAS as a result of the use of drugs from the group of ACE inhibitors influences the course of disease processes [35, 36].

Moreover, another study demonstrated a genetic influence of antihypertensive treatment and the effect of RAS blockers on the regression of LVH [37]. It is known that ACE inhibitors are among the basic drugs used in the treatment of patients with HF and asymptomatic left ventricular dysfunction, as they prevent disease progression, have protective effects of LVH, and reduce mortality and the frequency of hospitalization [35].

Although RAS is an important contributor to LVM modulation, the contribution and serious consequences of HT should be considered. In our study, we did not observe the influence of the studied genes on LVM in patients with HF who also had HT. We believe this finding can only confirm that proper treatment of HT can protect patients against myocardial hypertrophy. Many studies have shown that appropriate treatment of the effects of HT is associated with the regression of LVH [37, 38]; especially antihypertensive treatment with ACE inhibitors in patients with the DD genotype of the ACE gene presenting the best response to LVH regression [39].

The limitation of this study is the relatively small study group. Moreover, the etiology of HF in the study group is diverse, which may affect the obtained results.

HF is a complex disease and the genetic components involved in its development are based on the action of many genes. Of particular note is LVH in the course of HF, which is the main factor influencing the advancement of the disease process, and the exact mechanism of which is still not fully clear. As a result, the search for genes that can act as prognostic markers that could be used to predict poor outcomes and aid in selecting the appropriate therapeutic intervention is still ongoing. Further study on this complex system is necessary to improve medical therapies for cardiovascular diseases, allowing us to more adeptly modulate this system and improve clinical outcomes.

CONCLUSIONS

Our results suggested that polymorphism G(–6)A of the AGT gene may play a protective role in the development of HF in Polish patients. However, further multi-center studies of ethnically diverse populations are needed to confirm this finding in the future.

Article information

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