Effects of Different Blood Pressure–Lowering Regimens on Major Cardiovascular Events in Individuals With and Without Diabetes Mellitus

Turnbull, Fiona; Neal, Bruce; Algert, Charles S.; Chalmers, John; Chapman, Neil; Cutler, Jeff; Woodward, Mark; MacMahon, Stephen

doi:10.1001/archinte.165.12.1410

Cited by 691 publications

(85 citation statements)

References 20 publications

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“…Although increased cardiac expression of RAS components are linked to the pathogenesis of heart disease the outcomes of trials evaluating the efficacy of angiotensin converting enzyme (ACE) inhibitors, Ang II receptor blockers (ARBs) or a direct renin inhibitor have not fully achieved the benefits that would be expected from a robust experimental literature documenting Ang II as a cause of or a major contributor to the pathogenesis of heart disease (Disertori et al, 2012; Laight, 2009; Turnbull et al, 2005; Turnbull et al, 2007; Turnbull et al, 2008). To reconcile the gap between treatment effects in animal experiments and clinical trials results, proposed explanations include species differences in Ang II processing pathways in humans and animals (Balcells et al, 1997; Ferrario et al, 2005b), compensatory ACE inhibition escape (Ennezat et al, 2000; van den Meiracker et al, 1992), failure of drugs to access the intracellular sites at which Ang II acts (Baker et al, 1992; De Mello and Danser, 2000; Dostal and Baker, 1999; Kumar et al, 2012), or these factors in combination.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Differential expression of the angiotensin-(1-12)/chymase axis in human atrial tissue

Nagata

Varagić

Kon

et al. 2015

Therapeutic Advances in Cardiovascular Disease

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Objective Heart chymase rather than angiotensin converting enzyme has higher specificity for angiotensin (Ang) I conversion into Ang II in humans. A new pathway for direct cardiac Ang II generation has been revealed through the demonstration that Ang-(1-12) is cleaved by chymase to generate Ang II directly. We address here whether Ang-(1-12) and chymase gene expression and activity are detected in the atrial appendages of 44 patients (10 females) undergoing heart surgery for the correction of valvular heart disease, resistant atrial fibrillation or ischemic heart disease. Methods and Results Immunoreactive- (Ir-) Ang-(1-12) expression was 54% higher in left atrial compared to right atrial appendages and this was associated with higher abundance of left atrial appendage chymase gene transcripts and chymase activity but no differences in angiotensinogen mRNA. Atrial chymase enzymatic activity was highly correlated with left atrial but not right atrial enlargement as determined by echocardiography while both tyrosine hydroxylase and NPY atrial appendages mRNAs correlated with atrial angiotensinogen mRNAs. Conclusions Higher Ang-(1-12) expression and upregulation of chymase gene transcripts and enzymatic activity from the atrial appendages connected to the enlarged left versus right atrial chambers of subjects with left heart disease defines a role of this alternate Ang II forming pathway in the processes accompanying adverse atrial and ventricular remodeling.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Differential expression of the angiotensin-(1-12)/chymase axis in human atrial tissue

Nagata

Varagić

Kon

et al. 2015

Therapeutic Advances in Cardiovascular Disease

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“…Ten treatable risk factors have been associated with 90% of the risk of ischemic or hemorrhagic stroke (O'Donnell et al., 2010). The risk profile for occurrence of MI is quite different than that for stroke (Yusuf et al., 2004), but hypertension is one important risk factor for stroke, MI or vascular cause of death (Carlson & Böttiger, 1985; Conroy et al., 2003; Håheim et al., 1993; Harmsen et al., 1990; Hu et al., 2005; Psaty et al., 2001; Qizilbash, Lewington, Duffy, & Peto, 1995; Seshadri et al., 2006) and antihypertensive treatment(s) reduces these risks (Hackam & Spence, 2007; Hankey, 2014; Mancia et al., 2013; Turnbull, 2003; Turnbull et al., 2005; Wachtell, Hornestam, et al., 2005; Wachtell, Lehto, et al., 2005). …”

Section: Discussionmentioning

confidence: 99%

Secondary prophylactic treatment and long‐term prognosis after TIA and different subtypes of stroke. A 25‐year follow‐up hospital‐based observational study

Eriksson

2016

Brain and Behavior

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ObjectivesTo assess long‐term prognosis after transient ischemic attack (TIA)/subtypes of stroke relative to secondary prophylactic treatment(s) given.Materials and MethodsRetro/prospective follow‐up of patients hospitalized in the Stroke Unit or in the Department of Neurology, Linköping, in 1986 and followed up to Feb. 2011.ResultsA total of 288 men were followed up for 2254 years (mean 7.8 years) and 261 women for 1984 years (mean 7.6 years). In men, the distribution to anticoagulants (AC) (warfarin treatment) was 18%, antiplatelet therapy (APT) usually ASA 75 mg/day 54%, untreated 27%, unknown 2%. In women, the distribution to AC was 15%, APT 60%, untreated 23%, unknown 2%, respectively. Mortality rates at 1 year, 10 years, and 25 years for men were 21%, 67%, and 93%, respectively, versus the rates in women of 24%, 71%, and 90%, respectively. Survival curves showed markedly increased risk of death compared to the normal population. AC treatment was more favorable for men regarding the annual risk of stroke, compared with APT (9.4% vs. 9.8%), as well as the risks of MI, (5.6% vs. 6.7%), and death (8.1% vs. 10.3%), compared to women for stroke (11.6% vs. 8.8%) and MI (5.3% vs. 3.7%) but not for death (8.3% vs. 8.4%). The risk of fatal bleeding was 0.86% annually on AC compared to 0.17% on APT. According to Cox regression analysis included patients with TIA/ischemic stroke, first‐line treatment had beneficial effects on survival: AC OR 0.67 (0.5–0.9), APT 0.67 (0.52–0.88) versus untreated.ConclusionsPatients with a history of TIA/stroke had a higher mortality rate versus controls, providing support for both primary and secondary prophylaxis regarding vascular risk factors for death. This study also provided support for secondary prophylactic treatment with either AC or ASA (75 mg once daily) to reduce the vascular risk of death unless there are contraindications.

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“…thiazide diuretics, β-blockers, calcium channel blockers (CCBs), ACEIs and angiotensin receptor blockers (ARBs) [2,9,12,13]. A systematic review pooling the data from 27 randomized trials concluded that the risk of total major cardiovascular events was similarly reduced for patients with and without diabetes receiving BP-lowering regimens based on the five classes of AHDs [14]. However, with few exceptions, studies reported no significant general advantage of one drug over the other for cardiovascular outcomes following antihypertensive therapy in diabetes [2,12,14].…”

Section: Introductionmentioning

confidence: 99%

“…A systematic review pooling the data from 27 randomized trials concluded that the risk of total major cardiovascular events was similarly reduced for patients with and without diabetes receiving BP-lowering regimens based on the five classes of AHDs [14]. However, with few exceptions, studies reported no significant general advantage of one drug over the other for cardiovascular outcomes following antihypertensive therapy in diabetes [2,12,14]. A more recent review gathering data from clinical trials and literature of BP therapy also concluded that various AHDs had similar effectiveness in reducing coronary artery disease events, but showed a potential to result in worsened metabolic control in patients with diabetes [15].…”

Section: Introductionmentioning

confidence: 99%

Antihypertensive Drugs and Diabetic Retinopathy in Patients with Type 2 Diabetes

Lin

Lai²

2015

Ophthalmologica

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Objective: To evaluate the association between the development of sight-threatening diabetic retinopathy (STDR) and antihypertensive drugs (AHDs) use among type 2 diabetic patients with concomitant hypertension. Methods: Type 2 diabetic patients aged 20-100 years who had at least one prescription for AHDs between 2000 and 2011 were identified from the Longitudinal Health Insurance Database (LHID) 2005. The incidence rates of STDR were followed and Cox proportional hazard models were used to analyze the risk associated with AHDs. Results: Users of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) were associated with a significantly higher risk than users of calcium channel blockers (CCBs), independent of baseline characteristics. After adjusting for time-varying use of concomitant medications for propensity score-matched or -unmatched cohorts, the results showed that patients receiving ACEIs/ARBs and CCBs were associated with a significantly greater risk compared with β-blocker users. Conclusions: Our study did not support a superiority of ACEIs/ARBs and CCBs over β-blockers for lowering the progression of diabetic retinopathy.

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Effects of Different Blood Pressure–Lowering Regimens on Major Cardiovascular Events in Individuals With and Without Diabetes Mellitus

Cited by 691 publications

References 20 publications

RETRACTED: Differential expression of the angiotensin-(1-12)/chymase axis in human atrial tissue

RETRACTED: Differential expression of the angiotensin-(1-12)/chymase axis in human atrial tissue

Secondary prophylactic treatment and long‐term prognosis after TIA and different subtypes of stroke. A 25‐year follow‐up hospital‐based observational study

Antihypertensive Drugs and Diabetic Retinopathy in Patients with Type 2 Diabetes

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