Left Ventricular Mass in Relation to Genetic Variation in Angiotensin II Receptors, Renin System Genes, and Sodium Excretion

Kuznetsova, Tatiana; Staessen, Jan A.; Thijs, Lutgarde; Kunath, Christiane; Olszanecka, Agnieszka; Ryabikov, A.; Tikhonoff, Valérie; Stolarz, Katarzyna; Bianchi, Giuseppe; Casíglia, Edoardo; Fagard, Robert; Brand-Herrmann, Stefan-Martin; Kawecka‐Jaszcz, Kalina; Malyutina, Sofia; Nikitin, Yu. P.; Brand, Eva

doi:10.1161/01.cir.0000145541.63406.ba

Cited by 65 publications

(61 citation statements)

References 31 publications

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“…Our statistical methods also included single and multiple linear regressions. We included in our models covariables with known physiological relevance 12,20 for left ventricular structure. We additionally searched for possible covariables, using stepwise multiple regressions with the probability value for independent variables to enter and stay in the model set at 0.15.…”

Section: Methodsmentioning

confidence: 99%

Independent Relations of Left Ventricular Structure With the 24-Hour Urinary Excretion of Sodium and Aldosterone

et al. 2009

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Abstract-Previous studies reported on the association of left ventricular mass index (LVMI) with urinary sodium or with circulating or urinary aldosterone. We investigated the independent associations of LVMI with the urinary excretion of both sodium and aldosterone. We randomly recruited 317 untreated subjects from a white population (45.1% women; mean age 48.2 years). Measurements included echocardiographic left ventricular (LV) properties, the 24-hour urinary excretion of sodium and aldosterone, plasma renin activity (PRA), and proximal (RNa prox ) and distal (RNa dist ) renal sodium reabsorption, assessed from the endogenous lithium clearance. In multivariable-adjusted models, we expressed changes in LVMI per 1-SD increase in the explanatory variables, while accounting for sex, age, systolic blood pressure, and the waist-to-hip ratio. LVMI increased independently with the urinary excretion of both sodium (ϩ2.48 g/m 2 ; Pϭ0.005) and aldosterone (ϩ2.63 g/m 2 ; Pϭ0.004). Higher sodium excretion was associated with increased mean wall thickness (MWT: ϩ0.126 mm, Pϭ0.054), but with no change in LV end-diastolic diameter (LVID: ϩ0.12 mm, Pϭ0.64). In contrast, higher aldosterone excretion was associated with higher LVID (ϩ0.54 mm; Pϭ0.017), but with no change in MWT (ϩ0.070 mm; Pϭ0.28). Higher RNa dist was associated with lower relative wall thickness (Ϫ0.81ϫ10 Ϫ2 , Pϭ0.017), because of opposite trends in LVID (ϩ0.33 mm; Pϭ0.13) and MWT (Ϫ0.130 mm; Pϭ0.040). LVMI was not associated with PRA or RNa prox. In conclusion, LVMI independently increased with both urinary sodium and aldosterone excretion. Increased MWT explained the association of LVMI with urinary sodium and increased LVID the association of LVMI with urinary aldosterone. Key Words: aldosterone Ⅲ left ventricle Ⅲ plasma renin activity Ⅲ population science Ⅲ renal sodium handling E xperimental research in rats supports the hypothesis that dietary sodium intake might play a role in the pathogenesis of left ventricular hypertrophy. [1][2][3] Most, 4 -6 albeit not all, 7 studies in hypertensive patients noticed a significant association between left ventricular mass (LVM) and the urinary sodium excretion. However, in the Framingham Heart Study, 8 the association between LVM and the urinary sodium concentration indexed to creatinine was not significant. Furthermore, several studies in hypertensive patients 9 -11 or in populations 12,13 observed a positive association between LVM and either circulating 9 -13 or urinary 14 aldosterone. To our knowledge, none of the previous studies addressed the association between LVM and aldosterone, while accounting for urinary sodium excretion as index of salt intake, or vice versa.Measuring the clearance of endogenous lithium allows estimating sodium handling in the proximal and postproximal nephron. 15,16 In an attempt to address the aforementioned inconsistencies between studies in hypertensive patients and populations, and to gain further insight in the association between LVM and aldosterone, we studied in a random sa...

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Section: Methodsmentioning

confidence: 99%

Independent Relations of Left Ventricular Structure With the 24-Hour Urinary Excretion of Sodium and Aldosterone

et al. 2009

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“…In seven European countries, investigators randomly enrolled nuclear and extended families of White Caucasian ethnicity. Four centers took part in the substudy on echocardiography 10,11 and together enrolled 1522 subjects in Kraków (Poland; n¼325), Novosibirsk (Russian Federation; n¼301), Mirano (Italy; n¼345) and Hechtel-Eksel (Belgium; n¼551). The overall response rate was 67.8%.…”

Section: Study Populationmentioning

confidence: 99%

“…10,11 With subjects in left decubitus and breathing normally, the observers obtained Mmode echocardiograms of the left ventricle from the parasternal long-axis view under control of the two-dimensional image. They positioned the ultrasound beam just below the mitral valve at the level of the posterior chordae tendineae.…”

Section: Echocardiographic Measurementsmentioning

confidence: 99%

“…Lewontin's disequilibrium coefficient D' was 1.00 (Po0.0001). Population-based association study As in earlier analyses, 10,11 we adjusted the left ventricular phenotypes for center, sex, age, systolic blood pressure, body weight and height, waist-to-hip ratio, pulse rate, use of antihypertensive drugs and lifestyle factors, including smoking and alcohol consumption in excess of 5 g per day. Models with LVMI as the dependent variable were not adjusted for body weight and body height.…”

Section: Genotype Frequenciesmentioning

confidence: 99%

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Left ventricular structure in relation to the human SAH gene in the European Project on Genes in Hypertension

et al. 2009

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Earlier studies showed association of the human SAH (Spontaneously hypertensive rat-clone A-Hypertension associated) gene with hypertension and obesity. Left ventricular mass index (LVMI) increases with blood pressure and body mass index. In a family-based population study (54.5% women; mean age, 43.1 years), we measured LVMI, mean wall thickness (MWT) and the left ventricular internal diameter (LVID) at end-diastole in 699 non-Slavic and 493 Slavic participants. In multivariable-adjusted analyses, we investigated phenotype-genotype associations (SAH GÀ1606A and À962ins/del polymorphisms), while accounting for confounders and relatedness. Non-Slavic À1606GG homozygotes had a slightly greater LVID than À1606A allele carriers (48.6 vs. 48.0 mm; P¼0.08). However, the between-family component of the variance in LVID was significant (P¼0.005), suggesting that population stratification might explain the latter finding. Non-Slavic À962del carriers had higher LVMI (91.1 vs. 88.5 g m À2 ; P¼0.03) and MWT (9.61 vs. 9.44 mm; P¼0.03) than À962ins homozygotes. Transmission of the À962del to non-Slavic offspring was also associated with higher MWT (P¼0.03). In Slavic participants, in the absence of population stratification (PX0.69), À1606GG homozygotes had lower LVMI (96.5 vs. 102.3 g m À2 ; P¼0.004) and lower MWT (10.1 vs. 10.5 mm; P¼0.003) than À1606A carriers. Sensitivity analyses showed that the latter associations were confined to founders. Transmission of the À962del allele to Slavic offspring was associated with lower MWT (P¼0.007). In conclusion, LVMI and MWT, two phenotypes that are jointly influenced by blood pressure and obesity, might be related to variation in the human SAH gene.

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“…L191L is a synonymous base substitution in exon5 and Zhu et al ( 2003) found that it was associated with EH in AAs. A few studies assessed the association of A1166C with LVM, with negative findings in white subjects (Castellano et al, 1996;Kuznetsova et al, 2004).…”

Section: Effects Of Angiotensinogen and Angiotensin II Type I Receptomentioning

confidence: 99%

Effects of Angiotensinogen and Angiotensin II Type I Receptor Genes on Blood Pressure and Left Ventricular Mass Trajectories in Multiethnic Youth

et al. 2006

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T he objective of this study was to evaluate the impact of variations of the angiotensinogen (AGT) and angiotensin II type I receptor (AGTR1) genes on progression of blood pressure (BP) and left ventricular mass (LVM) in multiethnic youth. The study was longitudinal involving 581 European American (EA) and African American (AA) youth with 12 assessments over a 15-year period. AGT M235T and three AGTR1 polymorphisms (C-521T, L191L and A1166C) were genotyped and individual growth curve modeling analyses were conducted. Single nucleotide polymorphism (SNP) analyses found a significant 3-way interaction between M235T, ethnicity and gender on BP levels. Systolic BP (SBP) levels were 5.8 mmHg (p = .00003) and diastolic BP (DBP) levels were 2.6 mmHg (p = .005) lower in carriers versus noncarriers of the M235 allele in AA males only. Furthermore, the AGTR1 L191 allele showed a SBP lowering effect in subjects with a high socioeconomic status (SES; p = .048) and a DBP lowering effect in AAs (p = .038). Haplotype analyses identified a protective haplotype (C-521, 191L and A1166) for LVM levels (p = .03). LVM in individuals homozygous for this haplotype was 12.9 g lower than those homozygous for the most common haplotype (-521T, 191L and A1166). No significant interactions were found between the AGT M235T polymorphism and any of the single SNPs or haplotypes of the AGTR1 gene. Our results in multiethnic youth uncover an ethnicity and gender-specific effect of the AGT M235T polymorphism and a SES or ethnicity-specific effect of the AGTR1 L191L polymorphism on the progression of hypertension risk. A protective AGTR1 haplotype for LVM was also identified.

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Left Ventricular Mass in Relation to Genetic Variation in Angiotensin II Receptors, Renin System Genes, and Sodium Excretion

Cited by 65 publications

References 31 publications

Independent Relations of Left Ventricular Structure With the 24-Hour Urinary Excretion of Sodium and Aldosterone

Independent Relations of Left Ventricular Structure With the 24-Hour Urinary Excretion of Sodium and Aldosterone

Left ventricular structure in relation to the human SAH gene in the European Project on Genes in Hypertension

Effects of Angiotensinogen and Angiotensin II Type I Receptor Genes on Blood Pressure and Left Ventricular Mass Trajectories in Multiethnic Youth

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