Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2012

Open Access 01-12-2012 | Original investigation

Effects of candesartan in hypertensive patients with type 2 diabetes mellitus on inflammatory parameters and their relationship to pulse pressure

Authors: Masaya Sakamoto, Hirofumi Suzuki, Takeshi Hayashi, Hiroyuki Iuchi, Tsuyoshi Isaka, Noriko Sakamoto, Yosuke Kayama, Katsuyoshi Tojo, Michihiro Yoshimura, Kazunori Utsunomiya

Published in: Cardiovascular Diabetology | Issue 1/2012

Login to get access

Abstract

Background

Angiotensin receptor blockers (ARBs) are reported to provide direct protection to many organs by controlling inflammation and decreasing oxidant stress in patients without arteriosclerosis. This study aimed to evaluate (1) whether an ARB (candesartan) decreases values for inflammatory parameters in hypertensive patients with type 2 diabetes mellitus of long duration accompanied by arteriosclerosis and (2) whether there any predictors of which patients would receive the benefits of organ protection by candesartan.

Methods

We administered candesartan therapy (12 mg daily) for 6 months and evaluated whether there was improvement in serum inflammatory parameters high molecular weight adiponectin (HMW-ADN), plasminogen activator inhibitor-1 (PAI-1), highly sensitive C-reactive protein (Hs-CRP), vascular cell adhesion molecule-1 (VCAM-1) in serum and urinary-8-hydroxydeoxyguanosine (U-8-OHdG). We then analyzed the relationship between the degree of lowering of blood pressure and inflammatory factors and the relationship between pulse pressure and inflammatory factors. Finally, we analyzed predictive factors in patients who received the protective benefit of candesartan.

Results

After 6 months of treatment, significant improvements from baseline values were observed in all patients in HMW-ADN and PAI-1 but not in Hs-CRP, VCAM-1 and U-8-OHdG. Multilinear regression analysis was performed to determine which factors could best predict changes in HMW-ADN and PAI-1. Changes in blood pressure were not significant predictors of changes in metabolic factors in all patients. We found that the group with baseline pulse pressure <60 mmHg had improved HMW-ADN and PAI-1 values compared with the group with baseline pulse pressure ≥ 60 mmHg. These results suggest that pulse pressure at baseline could be predictive of changes in HMW-ADN and PAI-1.

Conclusions

Candesartan improved inflammatory parameters (HMW-ADN and PAI-1) in hypertensive patients with type 2 diabetes mellitus of long duration independent of blood pressure changes. Patients with pulse pressure <60 mmHg might receive protective benefits by candesartan.

Trial registration

UMIN000007921
Appendix
Available only for authorised users
Literature
1.
Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z: Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. J Clin Invest. 1985, 75: 809-817. 10.1172/JCI111776.PubMedCentralCrossRefPubMed
2.
Chen G, McAlister FA, Walker RL, Hemmelgarn BR, Campbell NR: Cardiovascular outcomes in Framingham participants with diabetes: the importance of blood pressure. Hypertension. 2011, 57: 891-897. 10.1161/HYPERTENSIONAHA.110.162446.PubMedCentralCrossRefPubMed
3.
UK Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998, 317: 703-713. 10.1136/bmj.317.7160.703.PubMedCentralCrossRef
4.
Stratton IM, Neil HA, Yudkin JS, Matthews DR, Cull CA, Wright AD, Turner RC, Holman RR, UK Prospective Diabetes Study Group Adler AI: Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000, 321: 412-419. 10.1136/bmj.321.7258.412.PubMedCentralCrossRefPubMed
5.
Evans GW, Byington RP, Goff DC, Grimm RH, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL, Katz L, Peterson KA, Friedewald WT, Buse JB, Bigger JT, Gerstein HC, Ismail-Beigi F, ACCORD Study Group, Cushman WC: Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010, 362: 1575-1585.CrossRefPubMed
6.
Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H: LIFE Study Group: Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002, 359: 995-1003. 10.1016/S0140-6736(02)08089-3.CrossRefPubMed
7.
Mallat SG: What is a preferred angiotensin II receptor blocker-based combination therapy for blood pressure control in hypertensive patients with diabetic and non-diabetic renal impairment?. Cardiovasc Diabetol. 2012, 11: 32-10.1186/1475-2840-11-32.PubMedCentralCrossRefPubMed
8.
McMurray JJ, Holman RR, Haffner SM, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamás G, Tognoni G, Tuomilehto J, Villamil AS, Vozár J, Califf RM, NAVIGATOR Study Group: Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010, 362: 1477-1490.CrossRefPubMed
9.
Ono H, Minatoguchi S, Watanabe K, Yamada Y, Mizukusa T, Kawasaki H, Takahashi H, Uno T, Tsukamoto T, Hiei K, Fujiwara H: Candesartan decreases carotid intima-media thickness by enhancing nitric oxide and decreasing oxidative stress in patients with hypertension. Hypertens Res. 2008, 31: 271-279. 10.1291/hypres.31.271.CrossRefPubMed
10.
Zou Y, Akazawa H, Qin Y, Sano M, Takano H, Minamino T, Makita N, Iwanaga K, Zhu W, Kudoh S, Toko H, Tamura K, Kihara M, Nagai T, Fukamizu A, Umemura S, Iiri T, Fujita T, Komuro I: Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol. 2004, 6: 499-506. 10.1038/ncb1137.CrossRefPubMed
11.
Shargorodsky M, Hass E, Boaz M, Gavish D, Zimlichman R: High dose treatment with angiotensin II receptor blocker in patients with hypertension: differential effect of tissue protection versus blood pressure lowering. Atherosclerosis. 2008, 197: 303-10. 10.1016/j.atherosclerosis.2006.12.036.CrossRefPubMed
12.
Nishida Y, Takahashi Y, Nakayama T, Soma M, Asai S: Comparative effect of olmesartan and candesartan on lipid metabolism and renal function in patients with hypertension: a retrospective observational study. Cardiovasc Diabetol. 2011, 10: 74-10.1186/1475-2840-10-74.PubMedCentralCrossRefPubMed
13.
Onozato ML, Tojo A, Goto A, Fujita T, Wilcox CS: Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: effects of ACEI and ARB. Kidney Int. 2002, 61: 186-194. 10.1046/j.1523-1755.2002.00123.x.CrossRefPubMed
14.
Franklin SS, Khan SA, Wong ND, Larson MG, Levy D: Is pulse pressure useful in predicting risk for coronary heart disease? The Framingham Heart Study. Circulation. 1999, 100: 354-360. 10.1161/01.CIR.100.4.354.CrossRefPubMed
15.
Kikuya M, Staessen JA, Ohkubo T, Thijs L, Metoki H, Asayama K, Obara T, Inoue R, Li Y, Dolan E, Hoshi H, Hashimoto J, Totsune K, Satoh H, Wang JG, O'Brien E, Imai Y: Ambulatory arterial stiffness index and 24-hour ambulatory pulse pressure as predictors of mortality in Ohasama, Japan. Stroke. 2007, 38: 1161-1166. 10.1161/01.STR.0000259604.67283.69.CrossRefPubMed
16.
Rodrigo E, Santos L, Piñera C, Quintanar JA, Ruiz JC, Fernández-Fresnedo G, Palomar R, Gómez-Alamillo C, Arias M: Early prediction of new-onset diabetes mellitus by fifth-day fasting plasma glucose, pulse pressure, and proteinuria. Transplant Proc. 2011, 43: 2208-2210. 10.1016/j.transproceed.2011.05.005.CrossRefPubMed
17.
Yu C, Gong R, Rifai A, Tolbert EM, Dworkin LD: Long-term, high-dosage candesartan suppresses inflammation and injury in chronic kidney disease: nonhemodynamic renal protection. J Am Soc Nephrol. 2007, 18: 750-759. 10.1681/ASN.2006070770.CrossRefPubMed
18.
Derosa G, Maffioli P, Salvadeo SA, Ferrari I, Gravina A, Mereu R, Palumbo I, D'Angelo A, Cicero AF: Candesartan effect on inflammation in hypertension. Hypertens Res. 2010, 33: 209-213. 10.1038/hr.2009.212.CrossRefPubMed
19.
Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, Funahashi T, Ouchi N, Walsh K: Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 2005, 10: 1096-1103.CrossRef
20.
Kawano T, Saito T, Yasu T, Saito T, Nakamura T, Namai K, Tamemoto H, Kawakami M, Saito M, Ishikawa SE: Close association of hypoadiponectinemia with arteriosclerosis obliterans and ischemic heart disease. Metabolism. 2005, 54: 653-656. 10.1016/j.metabol.2004.12.009.CrossRefPubMed
21.
Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y: Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002, 106: 2767-2770. 10.1161/01.CIR.0000042707.50032.19.CrossRefPubMed
22.
Al-Hamodi Z, Ismail IS, Saif-Ali R, Ahmed KA, Muniandy S: Association of plasminogen activator inhibitor-1 and tissue plasminogen activator with type 2 diabetes and metabolic syndrome in Malaysian subjects. Cardiovasc Diabetol. 2011, 10: 23-10.1186/1475-2840-10-23.PubMedCentralCrossRefPubMed
23.
Thögersen AM, Jansson JH, Boman K, Nilsson TK, Weinehall L, Huhtasaari F, Hallmans G: High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation. 1998, 98: 2241-2247. 10.1161/01.CIR.98.21.2241.CrossRefPubMed
24.
Hardison RM, Sobel BE, McBane RD 2nd BARI 2D Study Group: Comparison of plasminogen activator inhibitor-1, tissue type plasminogen activator antigen, fibrinogen, and D-dimer levels in various age decades in patients with type 2 diabetes mellitus and stable coronary artery disease (from the BARI 2D trial). Am J Cardiol. 2010, 105: 17-24. 10.1016/j.amjcard.2009.08.643.PubMedCentralCrossRefPubMed
25.
Bangalore S, Messerli FH, Franklin SS, Mancia G, Champion A, Pepine CJ: Pulse pressure and risk of cardiovascular outcomes in patients with hypertension and coronary artery disease: an INternational VErapamil SR-trandolapril STudy (INVEST) analysis. Eur Heart J. 2009, 30: 1395-1401. 10.1093/eurheartj/ehp109.CrossRefPubMed
26.
Russo D, Morrone LF, Brancaccio S, Napolitano P, Salvatore E, Spadola R, Imbriaco M, Russo CV, Andreucci VE: Pulse pressure and presence of coronary artery calcification. Clin J Am Soc Nephrol. 2009, 4: 316-322. 10.2215/CJN.02580508.PubMedCentralCrossRefPubMed
27.
Casiglia E, Tikhonoff V, Mazza A, Piccoli A, Pessina AC: Pulse pressure and coronary mortality in elderly men and women from general population. J Hum Hypertens. 2002, 9: 611-620.CrossRef
28.
Nilsson PM, Cederholm J, Eeg-Olofsson K, Eliasson B, Zethelius B, Gudbjörnsdóttir S, Swedish National Diabetes Register (NDR): Pulse pressure strongly predicts cardiovascular disease risk in patients with type 2 diabetes from the Swedish National Diabetes Register (NDR). Diabetes Metab. 2009, 35: 439-446. 10.1016/j.diabet.2009.04.010.CrossRefPubMed
29.
Masahiro K, Staessen JA, Takayoshi O, Lutgarde T, Hirohito M, Kei A, Taku O, Ryusuke I, Yan L, Eamon D, Haruhisa H, Junichiro H, Kazuhito T, Hiroshi S, Ji-Guang Wang E, Eoin O'B, Yutaka I: Ambulatory Arterial Stiffness Index and 24-Hour Ambulatory Pulse Pressure as Predictors of Mortality in Ohasama, Japan. Stroke. 2007, 38: 1161-1166. 10.1161/01.STR.0000259604.67283.69.CrossRef
30.
Assmann G, Cullen P, Evers T, Petzinna D, Schulte H: Importance of arterial pulse pressure as a predictor of coronary heart disease risk in PROCAM. Eur Heart J. 2005, 26: 2120-2126. 10.1093/eurheartj/ehi467.CrossRefPubMed
31.
Jager A, van Hinsbergh VW, Kostense PJ, Emeis JJ, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Stehouwer CD: Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study. Diabetes. 2000, 49: 485-491. 10.2337/diabetes.49.3.485.CrossRefPubMed
Metadata
Title
Effects of candesartan in hypertensive patients with type 2 diabetes mellitus on inflammatory parameters and their relationship to pulse pressure
Authors
Masaya Sakamoto
Hirofumi Suzuki
Takeshi Hayashi
Hiroyuki Iuchi
Tsuyoshi Isaka
Noriko Sakamoto
Yosuke Kayama
Katsuyoshi Tojo
Michihiro Yoshimura
Kazunori Utsunomiya
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2012
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-11-118

Other articles of this Issue 1/2012

Cardiovascular Diabetology 1/2012 Go to the issue

Original investigation

Advanced glycation end products impair the migration, adhesion and secretion potentials of late endothelial progenitor cells

Original investigation

Uric acid is an independent risk factor for carotid atherosclerosis in a Japanese elderly population without metabolic syndrome

Original investigation

Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low

Original investigation

Determinants of vascular function in patients with type 2 diabetes

Original investigation

Relation between augmentation index and adiponectin during one-year metformin treatment for nonalcoholic steatohepatosis: effects beyond glucose lowering?

Original investigation

Sex-specific outcomes of diabetic patients with acute myocardial infarction who have undergone percutaneous coronary intervention: a register linkage study

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits