Valsartan, Blood Pressure Reduction, and C-Reactive Protein

Ridker, Paul M.; Danielson, Eleanor; Rifai, Nader; Glynn, Robert J.

doi:10.1161/01.hyp.0000226046.58883.32

Cited by 126 publications

(69 citation statements)

References 45 publications

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“…20,36 The "RAS-inflammation hypothesis" is also supported by previous clinical work showing reduced C-reactive protein levels on ARB treatment. 41 Thus, for both pathways proposed to be involved in thiazideassociated insulin resistance, ie, lipid overfill and inflammation, excessive RAS activity and angiotensin II action, affected by elevated aldosterone in this study, may be important underlying mechanisms. However, either of the 2 could also be explained by alternative, RAS-independent mechanisms that are not fully understood.…”

Section: Discussionmentioning

confidence: 70%

Hydrochlorothiazide, but not Candesartan, Aggravates Insulin Resistance and Causes Visceral and Hepatic Fat Accumulation

et al. 2008

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Abstract-Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m 2 per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07Ϯ2.05, 6.63Ϯ2.04, and 6.90Ϯ2.10 mg/kg of body weight per minute, meanϮSD; PՅ0.01). Liver fat content was higher (PϽ0.05) following H than both P and C. The subcutaneous to visceral abdominal adipose tissue ratio was reduced following H versus C and P (PϽ0.01). Glycosylated hemoglobin, alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein levels were higher (PϽ0.05) after H, but not C, versus P. There were no changes in body fat, intramyocellular lipid, extramyocellular lipid, or first-phase insulin secretion. Blood pressure was reduced similarly by C and H versus P. In conclusion, visceral fat redistribution, liver fat accumulation, low-grade inflammation, and aggravated insulin resistance were demonstrated after hydrochlorothiazide but not candesartan treatment. These findings can partly explain the diabetogenic potential of thiazides. Key Words: insulin resistance Ⅲ visceral obesity Ⅲ liver fat Ⅲ glucose clamp Ⅲ magnetic resonance H ypertension is associated with an increased risk of development of type 2 diabetes mellitus (T2DM), and it is also an important component of the metabolic syndrome. 1 Obesity and insulin resistance appear to be central perturbations in this cluster of cardiovascular risk factors. 2 Among antihypertensive drugs, ␤-blocking agents and thiazide diuretics have been reported to impair insulin sensitivity and potentially increase the risk for T2DM. [3][4][5] The diabetogenic potential of thiazides has been implicated for single, as well as combination, therapy. 3,6 It has been attributed to increased hepatic glucose production, impaired peripheral glucose uptake, and hypokalemia-mediated ␤-cell dysfunction. 6 -8 In contrast, there are several studies suggesting that inhibition of the renin-angiotensin system (RAS) with angiotensinconverting enzyme inhibitors or blockers of the type 1 angioten...

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Section: Discussionmentioning

confidence: 70%

Hydrochlorothiazide, but not Candesartan, Aggravates Insulin Resistance and Causes Visceral and Hepatic Fat Accumulation

et al. 2008

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“…The studies have been carried out using ACE inhibitors (39,40), AT1R blockers (39,(41)(42)(43), beta blockers (44) and calcium channel blockers (45)(46)(47). In the present study we could follow-up 37 of 57 hypertensive subjects after they had started with antihypertensive treatment.…”

Section: Cell Adhesion Molecules In Hypertensionmentioning

confidence: 99%

Circulating levels of cell adhesion molecules in hypertension

Shalia

Mashru

Vasvani

et al. 2009

Indian J Clin Biochem

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“…[258]. Authors enrolled 1668 stage 2 hypertensives, treated with 160 mg valsartan or 160/12.5 mg valsartan/hydrochlorothiazide (HCTZ) once daily for 2 weeks with forced titration to 320 mg valsartan or 320/12.5 mg valsartan/HCTZ for an additional 4 weeks.…”

Section: Valsartan (Vs Atenolol)mentioning

confidence: 99%

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

Raimondo¹,

Tuttolomondo²,

Buttà³

et al. 2012

CPD

112

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Abstract:The role of inflammation in cardiovascular disease and in hypertensive disease above all, is complex. Several studies confirm that activation of renin-angiotensin-aldosteron system (RAAS), through increase in the production of angiotensin II (Ang II), is closely related to local vascular inflammation. Over the BP lowering effects of anti-hypertensive treatments, several ancillary effects for every class may be found, distinguishing the various drugs from one another. Given the pro-inflammatory effects of Ang II and aldosterone, agents that interfere with the components of RAAS, such as ACE inhibitors, Angiotensin Recpetor Blockers (ARBs), and mineralocorticoid receptor antagonists (spironolactone or the more selective eplerenone), represent logical therapeutic tools to reduce vascular inflammation and cardiovascular risk, as suggested in large clinical trials in patients with hypertension and diabetes. Regarding ACE inhibitors, actually there is no convincing evidence indicating that ACEi's reduce plasma levels of major inflammatory markers in hypertension models. Lack of evidence concerns especially these inflammation markers, such as fibrinogen of CRP, which are less closely related to atherosclerotic disease and vascular damage and conversely are affected by several more aspecific factors. Results obtained by trials accomplished using ARBs seem to be more univocal to confirm, although to great extent, these is an anti-inflmmatory effect of drugs bocking AT1 receptor. In order to strictly study the effects of blockage of RAAS on inflammation, future studies may explore different strategies by, for example, simultaneously acting on the ACE and the AT1 angiotensin receptors.

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Valsartan, Blood Pressure Reduction, and C-Reactive Protein

Cited by 126 publications

References 45 publications

Hydrochlorothiazide, but not Candesartan, Aggravates Insulin Resistance and Causes Visceral and Hepatic Fat Accumulation

Hydrochlorothiazide, but not Candesartan, Aggravates Insulin Resistance and Causes Visceral and Hepatic Fat Accumulation

Circulating levels of cell adhesion molecules in hypertension

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

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