Lack of regression of left ventricular hypertrophy is associated with higher incidence of revascularization in hypertension: The LIFE Study

Søraas, Camilla Lund; Wachtell, Kristian; Okin, Peter M.; Dahlöf, Björn; Devereux, Richard B.; Tønnessen, Theis; Kjeldsen, Sverre E.; Olsen, Michael Hecht

doi:10.3109/08037051.2010.481812

Cited by 2 publications

(3 citation statements)

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“…Of the modifiable risk factors, elevated BP is the strongest contributor to cardiovascular events. 2,15 The SPRINT study (Systolic Blood Pressure Intervention Trial) and meta-analysis including 44 989 participants have demonstrated additional benefits from more intensive BP lowering in populations at high risk of vascular disease. 6,7 Up until now, data on outcomes in hypertension-treated patients with PAD have been lacking.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Outcomes in Hypertension-Treated Patients With Peripheral Artery Disease: The VALUE Trial

Vrsalovic,

Heimark,

Søraas

et al. 2024

Hypertension

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BACKGROUND: Systolic blood pressure (BP) is a key predictor of cardiovascular events, but patients with peripheral artery disease (PAD) are rarely included in hypertension trials. The VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation) investigated the long-term effects of valsartan- or amlodipine-based treatments on cardiovascular outcomes in patients with hypertension with a high cardiovascular risk. The aim of this subanalysis was to clarify the relationship between achieved BP on treatment and cardiovascular outcomes in patients with hypertension with PAD. METHODS: Patients were followed for 4 to 6 years, and BP was measured regularly. The primary end point was time to the first major adverse cardiovascular event, including myocardial infarction, stroke, cardiovascular death, and heart failure requiring hospitalization. Statistical analyses were performed using Cox regression, adjusting for various baseline covariates. RESULTS: Of the 13 803 participants, 1898 (13.8%) had PAD. During a median follow-up of 4.5 years, patients with PAD had a 23% increased risk of major adverse cardiovascular events compared with patients without PAD. Patients with an achieved systolic BP <130 mm Hg and 130 to 139 mm Hg, compared with those with systolic BP ≥140 mm Hg, were associated with a decreased risk of a major adverse cardiovascular event (hazard ratio, 0.65 [95% CI, 0.43–0.97]; P =0.037; 0.85 [95% CI, 0.74–0.97]; P =0.016, respectively). Additionally, systolic BP <130 mm Hg was associated with a decreased risk of cardiovascular death (hazard ratio, 0.33 [95% CI, 0.12–0.92]; P =0.034). The incidence of the primary outcome did not differ between antihypertensive treatment regimens ( P =0.365). CONCLUSIONS: Our results indicate that more intensive BP control is associated with a reduction in cardiovascular morbidity and mortality in patients with hypertensive PAD.

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Section: Discussionmentioning

confidence: 99%

Cardiovascular Outcomes in Hypertension-Treated Patients With Peripheral Artery Disease: The VALUE Trial

Vrsalovic,

Heimark,

Søraas

et al. 2024

Hypertension

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“…This process is termed cardiac remodelling and eventually leads to heart failure. Pathological cardiac hypertrophy has been recognized as an important predictor for cardiovascular morbidity and mortality as well as an independent risk factor for heart failure, myocardial infarction, arrhythmias and sudden death (Wachtell et al, 2007;Artham et al, 2009;Bombelli et al, 2009;Søraas et al, 2010).…”

Section: Types Of Cardiac Hypertrophymentioning

confidence: 99%

“…The presence of cardiac hypertrophy is usually an adverse characteristic of various cardiovascular disorders, and regression or prevention of cardiac hypertrophy has benefits in reducing the risk of CV events and sudden cardiac death in the hypertensive population (Wachtell et al, 2007;Artham et al, 2009;Bombelli et al, 2009;Søraas et al, 2010). As hypertension is commonly associated with the development of pathological left ventricle hypertrophy (LVH), most anti-hypertensive drugs can attenuate LVH, such as angiotensin converting enzyme (ACE) inhibitors and Ang II type 1 receptor (AT 1 R) blockers (ARB) (Solomon et al, 2011;Müller et al, 2012), calcium channel blockers (Devereux et al, 2001), and β-blockers (Cabrera- Bueno et al, 2007).…”

Section: Therapy For Cardiac Hypertrophymentioning

confidence: 99%

Investigations into the role of the ErbB4 receptor in cardiomyocyte hypertrophy and adult cardiac function

Wang¹

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ErbB receptors (ErbB1 -ErbB4) are a subfamily of tyrosine kinase receptors that regulate cell proliferation and differentiation. It has been proposed that the ErbB1 subtype is transactivated by Ang II to mediate cardiac hypertrophy. However, whether other ErbB receptors, in particular the abundant subtype ErbB4, are involved in this process is not known. ErbB4 has four isoforms due to alternative splicing, each of which might play a distinct role in regulating cell activity. However, the role of individual ErbB4 isoforms in hypertrophic signalling has not been investigated. In addition, ErbB4 activation is critical for cardiac development, cardiomyocyte survival in various rodent models of cardiovascular pathologies. However, the physiological role of ErbB4 in the adult heart remains poorly understood. The overall aim of my PhD project is to examine the role of the ErbB4 receptor in mediating hypertrophic growth of cardiomyocytes in vitro, and maintenance of the adult heart in vivo.To investigate the role of ErbB1, ErbB2 and ErbB4 in mediating hypertrophy, I inhibited individual ErbB receptors in primary neonatal rat ventricular cardiomyocytes using RNA interference or a pharmacological inhibitor (AG1478). Hypertrophy induced with Ang II (100 nM) or NRG1 (10 nM) was assessed by measuring the promoter activity of hypertrophic genes, ERK1/2 activation, and hypertrophic growth. The NRG1-induced hypertrophy was reduced by down-regulation of Following the studies above, I investigated whether the different ErbB4 isoforms had any functional differences in the cardiomyocytes. Irrespective of any changes in total ErbB4 mRNA levels, expression of the non-cleavable JM-b isoform was always predominant in adult heart in both physiological and pathological conditions. Although the cleavable isoform JM-a was detectable, it is not cleaved in cardiomyocytes. I replaced the endogenous ErbB4 with exogenous individual isoform in cardiomyocytes and found that all four isoforms of ErbB4 could mediate the NRG1-induced hypertrophic signalling. This suggests that the hypertrophy is triggered by a common feature of the four isoforms (ostensibly the kinase activity), and appears independent of isoformspecific features, such as the cleavable domain.To investigate the physiological function of ErbB4 in adult heart, we adopted the tamoxifeniii inducible αMHC-MerCreMer/loxP system to induce ErbB4 deletion from cardiomyocytes in the adult mouse. The expression of ErbB4 was reduced by ~ 90% at 10 days after tamoxifen treatment. Echocardiography revealed no differences in cardiac function (fractional shortening) betweenErbB4-conditional knockout (ErbB4-cKO) and control groups at 3-4 months after deletion of ErbB4. However, the heart weight was increased in ErbB4-cKO animals. Interestingly, there is no change in cardiac structure (cardiomyocyte size and cardiac fibrosis) or the expression of genes associated with pathological hypertrophy. This suggests that the cardiac hypertrophy observed following ErbB4 deletion may be physiological, a...

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Lack of regression of left ventricular hypertrophy is associated with higher incidence of revascularization in hypertension: The LIFE Study

Abstract: Higher Sokolow-Lyon voltage during antihypertensive treatment, but not UACR or the Cornell voltage-duration product, was independently associated with higher incidence of coronary as well as peripheral revascularization.

Cited by 2 publications

References 29 publications

Cardiovascular Outcomes in Hypertension-Treated Patients With Peripheral Artery Disease: The VALUE Trial

Cardiovascular Outcomes in Hypertension-Treated Patients With Peripheral Artery Disease: The VALUE Trial

Investigations into the role of the ErbB4 receptor in cardiomyocyte hypertrophy and adult cardiac function

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