Evidence of a Partial Escape of Renin‐Angiotensin‐Aldosterone Blockade in Patients with Acute Myocardial Infarction Treated with Ace Inhibitors

Borghi, Claudio; Boschi, Stefano; Ambrosioni, Ettore; Melandri, Giovanni; Branzi, Angelo; Magnani, B

doi:10.1002/j.1552-4604.1993.tb03901.x

Cited by 126 publications

(56 citation statements)

References 19 publications

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“…[3][4][5][6][7][8] Although previous studies have reported high plasma aldosterone levels in myocardial infarction, these observations have most often been limited by their small sample size, heterogeneous study populations, late measurements of aldosterone (often days to months after the onset of myocardial infarction), and inconclusive results with regard to the association of aldosterone with further clinical events. 9 -12 The aim of the present study was to assess early plasma aldosterone release in patients presenting with ST-elevation myocardial infarction (STEMI) within 24 hours of symptom onset and to determine whether aldosterone levels are related to adverse outcomes in this setting.…”

Section: Editorial P 2572 Clinical Perspective P 2610mentioning

confidence: 99%

High Plasma Aldosterone Levels on Admission Are Associated With Death in Patients Presenting With Acute ST-Elevation Myocardial Infarction

et al. 2006

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Background-Aldosterone, the final mediator of the renin-angiotensin-aldosterone pathway, is at its highest plasma levels at presentation for ST-elevation myocardial infarction (STEMI). Whether aldosterone level at presentation for STEMI is associated with adverse outcome remains unknown. Methods and Results-Plasma aldosterone levels were measured at presentation in consecutive patients referred for primary percutaneous coronary intervention for STEMI. We assessed the association between aldosterone levels and in-hospital events and mortality during a 6-month follow-up. Of 356 STEMI patients, 23 and 36 died during the hospital stay and 6-month follow-up period, respectively. Nine other patients survived in-hospital cardiac arrest. High aldosterone levels were associated with an almost stepwise increase in rates of in-hospital death (Pϭ0.01), cardiovascular death (Pϭ0.03), heart failure (Pϭ0.005), ventricular fibrillation (Pϭ0.02), and resuscitated cardiac arrest (Pϭ0.01). After adjustment for age, Killip class, and reperfusion status, compared with patients in the first aldosterone quartile group, those in the highest quartile were at higher risk of death (hazard ratio 3.28, 95% CI 1.09 to 9.89, Pϭ0.035) and death or resuscitated cardiac arrest (hazard ratio 3.74, 95% CI 1.40 to 9.98, Pϭ0.008) during the follow-up. Conclusions-Plasma aldosterone levels on admission among patients referred for primary percutaneous coronary intervention for STEMI are associated with early and late adverse clinical outcomes, including mortality. The association between high aldosterone levels and late mortality is independent of age, heart failure, and reperfusion status. Such results underline the pivotal role of aldosterone and justify a randomized trial to assess the early administration of aldosterone antagonists in the setting of STEMI.

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Section: Editorial P 2572 Clinical Perspective P 2610mentioning

confidence: 99%

High Plasma Aldosterone Levels on Admission Are Associated With Death in Patients Presenting With Acute ST-Elevation Myocardial Infarction

et al. 2006

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“…The increase in renin activity stimulates the conversion of Ang I and ultimately Ang II, which largely limits the efficacy of RAS inhibition (27,28). The increased renin can also act through the prorenin/ renin receptor (10), which may cause renal and cardiovascular damages independent of Ang II (29).…”

mentioning

confidence: 99%

Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: Blockade of compensatory renin increase

Zhang

Ning

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

262

225

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The renin-angiotensin system (RAS) plays a critical role in the development of diabetic nephropathy, and blockade of the RAS is currently used for treatment of diabetic nephropathy. One major problem for the current RAS inhibitors is the compensatory renin increase, which reduces the efficacy of RAS inhibition. We albuminuria ͉ glomerulosclerosis ͉ renin-angiotensin system D iabetic nephropathy is the most common renal complication that often leads to end-stage kidney disease and high mortality (1). Previous studies have suggested the renin-angiotensin system (RAS) as a major mediator of progressive renal injury in diabetic nephropathy. Drugs targeting the RAS including angiotensin (Ang)-converting enzyme inhibitors (ACEIs) and Ang II type 1 receptor blockers (ARBs) have been shown to reduce the progression of glomerulosclerosis, tubulointerstitial fibrosis, and proteinuria (2-6). The systemic components of the RAS are actually down-regulated in diabetic mellitus (7), whereas renal interstitial Ang II levels are estimated to be 1,000-fold higher than in the plasma (8); therefore, intrarenal RAS is thought to play the major damaging role. In fact, all components of the RAS are present within the kidney (9). Cells in the kidney are able to synthesize renin, prorenin/renin receptor (10), angiotensinogen, and Ang II receptors independent of the systemic RAS (11), making the kidney capable of maintaining a high level of intrarenal Ang II. Intrarenal renin and angiotensinogen levels are induced in diabetic animals (12, 13), and high glucose has been shown to stimulate renin and Ang II synthesis in mesangial cells and podocytes (14-16). Intrarenal Ang II exerts multiple effects on the kidney that promote the progression of renal injury; these include an increase in glomerular capillary pressure, induction of profibrotic and proinflammatory cytokine production, promotion of immune cell infiltration, stimulation of cell proliferation and hypertrophy, up-regulation of extracellular matrix (ECM) synthesis, and damaging of podocytes (17)(18)(19) (21), and null mutant mice lacking the vitamin D receptor (VDR) gene develop hyperreninemia, high blood pressure, and cardiac hypertrophy (22)(23)(24). Our recent studies showed that in diabetic state VDR-null mice developed more severe nephropathy than wild-type mice (25), suggesting that vitamin D plays a protective role against hyperglycemia-induced renal injury by regulation of the RAS. However, whether vitamin D or vitamin D analogs have therapeutic effects in intervention or prevention of diabetic nephropathy remains to be tested.Although RAS inhibitors, including ACEIs and ARBs, are widely used in the therapy of renal and cardiovascular diseases, the major problem of these drugs is the compensatory renin rise due to the disruption of the feedback inhibition of renin production (26). The increase in renin activity stimulates the conversion of Ang I and ultimately Ang II, which largely limits the efficacy of RAS inhibition (27,28). The increased renin can also act through the...

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“…This unfortunately is not the case. Several investigators have demonstrated that the use of ACEinhibitors initially causes an acute decrease in the concentration of aldosterone, but with continued use, this suppression is not sustained (59)(60)(61)(62).…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Aldosterone as a Mediator of Progressive Renal Dysfunction: Evolving Perspectives.

Epstein

2001

Intern. Med.

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End-stage renal disease (ESRD)comprises an enormous public health burden, with an incidence and prevalence that are increasingly on the rise. This escalating prevalence suggests that newer therapeutic interventions and strategies are neededto complement current therapeutic approaches. Although much evidence demonstrates conclusively that angiotensin II mediates progressive renal disease, recent evidence also implicates aldosterone as an important pathogenetic factor in progressive renal disease. Recently, several lines of experimental evidence demonstrate that selective blockade of aldosterone, independent of renin-angiotensin blockade, reduces proteinuria and nephrosclerosis in the spontaneously hypertensive stroke-prone rat (SHRSP) model and reduces proteinuria and glomerulosclerosis in the subtotally nephrectomized rat model (ie, remnant kidney). Whereas pharmacologic blockade with angiotensin II receptor blockers and angiotensin-converting enzyme (ACE)inhibitors reduces proteinuria and nephrosclerosis/glomerulosclerosis, selective rein fusion of aldosterone restores these abnormalities despite continued renin-angiotensin blockade. Aldosterone may promote fibrosis by several mechanisms, including plasminogen activator inhibitor-1 (PAI-1) expression and consequent alterations of vascular fibrinolysis, by stimulation of transforming growth factor-betal , and by stimulation of reactive oxygen species (ROS). Based on this formulation, randomized clinical studies will be initiated to delineate the potential renal-protective effects of aldosterone receptor blockade. (Internal Medicine 40: 573-583, 2001) Keywords: aldosterone receptor antagonist, renin-angiotensin system, end-stage renal disease (ESRD), diabetic nephropathy, plasminogen activator inhibitor-1 (PAI-1)

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Evidence of a Partial Escape of Renin‐Angiotensin‐Aldosterone Blockade in Patients with Acute Myocardial Infarction Treated with Ace Inhibitors

Cited by 126 publications

References 19 publications

High Plasma Aldosterone Levels on Admission Are Associated With Death in Patients Presenting With Acute ST-Elevation Myocardial Infarction

High Plasma Aldosterone Levels on Admission Are Associated With Death in Patients Presenting With Acute ST-Elevation Myocardial Infarction

Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: Blockade of compensatory renin increase

Aldosterone as a Mediator of Progressive Renal Dysfunction: Evolving Perspectives.

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