Associations between circulating components of the renin-angiotensin-aldosterone system and left ventricular mass.

Schunkert, Heribert; Hense, Hans‐Werner; Muscholl, M.; Luchner, Andreas; Kürzinger, Susanne; Danser, A.H. Jan; Riegger, Günter A.J.

doi:10.1136/hrt.77.1.24

Cited by 112 publications

(68 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5 Significant positive correlations have been observed between serum aldosterone and measures of heart size in humans. 6 Furthermore, aldosterone has direct cardiac cellular effects, including stimulation of fibroblast proliferation and collagen deposition by activation of local mineralocorticoid receptors. 7 The direct effects of aldosterone on cardiac structure, coupled with the association of CYP11B2 gene variants with plasma aldosterone levels, has led to the hypothesis that common polymorphisms in the CYP11B2 gene may influence cardiac size.…”

Section: Introductionmentioning

confidence: 99%

Measured haplotype analysis of the aldosterone synthase gene and heart size

et al. 2003

View full text Add to dashboard Cite

Gene-association studies of heart size and the aldosterone synthase (CYP11B2) gene have produced inconsistent results, possibly because of limitations in the sample size and/or the number and location of the polymorphisms. An analysis of six polymorphisms spanning 6 kb of the CYP11B2 gene in Caucasian British families revealed a limited number of haplotypes because of strong linkage disequilibrium over this small region. The genotype and haplotype information was used in an association study involving 955 members of 229 families phenotyped for echocardiographic measures of heart size. In a mixed effects linear modelling analysis, the G5937C polymorphism was associated with cardiac wall thickness (P ¼ 0.02), and the intron conversion and A4550C polymorphisms were associated with left ventricular cavity size (P ¼ 0.02 and 0.002, respectively). Measured haplotype analyses confirmed the association of alleles at the intron conversion and G5937C polymorphisms with cardiac wall thickness (P ¼ 0.02), and alleles at the intron conversion polymorphism with left ventricular cavity size (P ¼ 0.04). The polymorphisms contributed to 2.0 -3.4% of the variability in these traits. In summary, genetic polymorphisms at the CYP11B2 gene make a small contribution to quantitative variation in echocardiographic measures of heart size. These results point to the importance of analysing the full extent of genetic variation that captures the haplotype structure of a locus in gene association studies.

show abstract

Section: Introductionmentioning

confidence: 99%

Measured haplotype analysis of the aldosterone synthase gene and heart size

et al. 2003

View full text Add to dashboard Cite

show abstract

“…[24][25][26] It has been suggested that hypertensive incidents and organ damage in humans may occur even at plasma aldosterone levels within the normal physiological range. 24,[27][28][29] Therefore, targeting aldosterone synthesis and release may be clinically important in preventing cardiovascular disease. Ca 2+ ions are conveyed through the T-type Ca channel to the mitochondria, where they activate aldosterone synthesis, which in turn stimulates T-type Ca channel expression, 30,31 creating a positive feedback loop of aldosterone biosynthesis in adrenal cells.…”

Section: Discussionmentioning

confidence: 99%

Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria

et al. 2010

View full text Add to dashboard Cite

Benidipine inhibits both L-and T-type Ca channels, and has been shown to dilate the efferent arterioles as effectively as the afferent arterioles. In this study, we conducted an open-label and randomized trial to compare the effects of benidipine with those of amlodipine on blood pressure (BP), albuminuria and aldosterone concentration in hypertensive patients with mild-tomoderate stage chronic kidney disease (CKD). Patients with BPX130/80 mm Hg, with estimated glomerular filtration rate (eGFR) of 30-90 ml min À1 per 1.73 m 2 , and with albuminuria430 mg per g creatinine (Cr), despite treatment with the maximum recommended dose of angiotensin II receptor blockers (ARBs) were randomly assigned to two groups. Patients received either of the following two treatment regimens: 2 mg per day benidipine, which was increased up to a dose of 8 mg per day (n¼52), or 2.5 mg per day amlodipine, which was increased up to a dose of 10 mg per day (n¼52). After 6 months of treatment, a significant and comparable reduction in the systolic and diastolic BP was observed in both groups. The decrease in the urinary albumin to Cr ratio in the benidipine group was significantly lower than that in the amlodipine group. Although plasma renin activity was not different in the two groups, plasma aldosterone levels were significantly decreased in the benidipine group. Moreover, urinary Na/K ratio was significantly decreased in the benidipine group but remained unchanged in the serum. It may be concluded that benidipine results in a greater reduction of plasma aldosterone and albuminuria than amlodipine, and that these effects are independent of BP reduction.

show abstract

“…21 Aldosterone has been shown to promote cardiac fibrosis in various experimental models 22,23 and to promote adverse ventricular remodeling in humans. 4,5 Furthermore, aldosterone antagonism has been reported to reduce perivascular and interstitial fibrosis and to improve myocardial compliance. 24 Although no direct measurement of ventricular remodeling was made in RALES, indirect evidence for an improvement in left ventricular remodeling comes from a substudy of collagen formation.…”

mentioning

confidence: 99%

Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure

et al. 2003

View full text Add to dashboard Cite

MD; for the Valsartan Heart Failure Trial InvestigatorsBackground-Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure. Methods and Results-Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150Ϯ160 pg/mL, meanϮSD; nϭ2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137Ϯ124 pg/mL, meanϮSD; nϭ2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8Ϯ3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8Ϯ3.0 pg/mL (SEM) (Ϫ17.4%) in the valsartan group (PϽ0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor ␤-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs. Conclusions-Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure. Key Words: heart failure Ⅲ angiotensin Ⅲ trials D espite the remarkable success of ACE inhibitors (ACE-I) in reducing the mortality and morbidity from heart failure (HF), the addition of the aldosterone inhibitor spironolactone was shown to cause an additional 30% decrease in mortality in the Randomized Aldactone Evaluation Study (RALES). 1 Although ACE-I might be expected to reduce aldosterone levels by reducing the stimulating effect of angiotensin II on aldosterone production, recent studies have demonstrated that neither angiotensin II nor aldosterone plasma levels are suppressed chronically by clinically prescribed doses of ACE-I. 2,3 Aldosterone has been implicated as a contributor to structural remodeling of the left ventricle, 4 -6 and the beneficial effects of spironolactone on mortality have been attributed to inhibition of the collagen-generating influence of aldosterone. 7,8 Aldosterone secretion is stimulated by several factors in addition to angiotensin II, and these alternate mechanisms may be important determinants of aldosterone production and its levels in the plasma and tissues in patients with HF. In...

show abstract

Associations between circulating components of the renin-angiotensin-aldosterone system and left ventricular mass.

Cited by 112 publications

References 59 publications

Measured haplotype analysis of the aldosterone synthase gene and heart size

Measured haplotype analysis of the aldosterone synthase gene and heart size

Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria

Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure

Contact Info

Product

Resources

About