Hemodynamic and metabolic responses to valsartan and atenolol in obese hypertensive patients
Abstract
OBJECTIVE: None of the current hypertension guidelines provides specific guidance regarding pharmacological management of obese hypertensive patients. Treatment recommendations for lean hypertensives may not be simply extrapolated to obese hypertensive persons. DESIGN: Randomized, double-blind, parallel-group study with a 13-week treatment period. SETTING: Multicenter study in Germany. PATIENTS: Obese patients with mild to moderate uncomplicated essential hypertension. INTERVENTION: Patients were treated with valsartan at a maximal dose of 160 mg/day or with atenolol at a maximal dose of 100 mg/day. Hydrochlorothiazide at doses of 12.5-25 mg was added in patients with blood pressure > 140/90 mmHg on monotherapy. MAIN OUTCOME MEASURES: Blood pressure, lipid and glucose metabolism, and highly sensitive C-reactive protein (hsCRP) were monitored. RESULTS: Sixty-seven patients were randomized to valsartan and 65 patients to atenolol. With valsartan, systolic blood pressure (SBP) decreased from 160.8 +/- 8.9 to 140.5 +/- 13.3 mmHg and diastolic blood pressure (DBP) from 96.1 +/- 7.0 to 85.1 +/- 8.1 mmHg by the end of the study. With atenolol, SBP decreased from 159.3 +/- 6.8 to 139.8 +/- 14.5 mmHg and DBP from 95.0 +/- 6.8 to 83.5 +/- 7.5 mmHg (P = 0.91 for SBP and P = 0.34 for DBP between interventions). Body weight did not change with either treatment. We did not see a significant difference in the response of lipid levels or hsCRP between interventions. To assess the cumulative effect of each intervention on glucose metabolism over the trial duration, we calculated individual areas under the curve for homeostasis model assessment for insulin resistance (HOMA-IR) over time. The resulting area under the curve was significantly smaller with valsartan compared with atenolol (P = 0.02). CONCLUSIONS: Beta-adrenoreceptor blockers and AT1-receptor blockers, particularly in combination with low-dose diuretics, effectively lower blood pressure in obese hypertensives. However, metabolic responses differ between both treatment strategies, with beneficial effects of AT1-receptor blockers. AT1-receptor blockers are a good choice in obese hypertensives, given the profoundly increased diabetes risk in this population.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Treatment with β-blockers leads to metabolic complications including weight gain.
“Given that excessive sympathetic activity is common in obesity, β-blockers appear as an obvious pharmacologic therapy to treat the hypertension associated with this condition, but treatment with β-blockers leads to metabolic complications including weight gain (16–18).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [18]
Cites
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944 · see citing works
Expert Panel on Detection, E. (2001) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.285.19.2486 · Cited by 26,011 · see citing works
The Disease Burden Associated With Overweight and Obesity
Must, A. (1999) · JAMA · doi:10.1001/jama.282.16.1523 · Cited by 4,804 · see citing works
Obesity, Fat Distribution, and Weight Gain as Risk Factors for Clinical Diabetes in Men
Chan, J. M., Rimm, E. B., Colditz, G. A., Stampfer, M. J., & Willett, W. C. (1994) · Diabetes Care · doi:10.2337/diacare.17.9.961 · Cited by 1,808 · see citing works
Tuck, M. L., Sowers, J. R., Dornfeld, L., Kledzik, G. S., & Maxwell, M. H. (1981) · New England Journal of Medicine · doi:10.1056/nejm198104163041602 · Cited by 643 · see citing works
Weight Loss and the Renin-Angiotensin-Aldosterone System
Engeli, S., Böhnke, J., Gorzelniak, K., Janke, J., Schling, P., Bäder, M., Luft, F. C., & Sharma, A. M. (2005) · Hypertension · doi:10.1161/01.hyp.0000154361.47683.d3 · Cited by 625 · see citing works
Self-citationAdipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation
Massiéra, F., Bloch-Faure, M., Ceiler, D. L., Murakami, K., Fukamizu, A., Gasc, J., Quignard‐Boulangé, A., Négrel, R., Ailhaud, G. P., Seydoux, J., et al. (2001) · The FASEB Journal · doi:10.1096/fj.01-0457fje · Cited by 505 · see citing works
Neural mechanisms in human obesity-related hypertension
Rumantir, M. S., Vaz, M., Jennings, G. L., Collier, G., Kaye, D. M., Seals, D. R., Wiesner, G. H., Brunner-La Rocca, H. P., & Esler, M. D. (1999) · Journal of Hypertension · doi:10.1097/00004872-199917080-00012 · Cited by 396 · see citing works
Hypothesis: β-Adrenergic Receptor Blockers and Weight Gain
Sharma, A. M., Pischon, T., Hardt, S., Kunz, I., & Luft, F. C. (2001) · Hypertension · doi:10.1161/01.hyp.37.2.250 · Cited by 339 · see citing works
Self-citationDoll, S., Paccaud, F. M., Bovet, P., Burnier, M., & Wietlisbach, V. (2002) · International Journal of Obesity · doi:10.1038/sj.ijo.0801854 · Cited by 308 · see citing works
Adrenergic and Reflex Abnormalities in Obesity-Related Hypertension
Grassi, G., Seravalle, G., Dell’Oro, R., Turri, C., Bolla, G. B., & Mancia, G. (2000) · Hypertension · doi:10.1161/01.hyp.36.4.538 · Cited by 305 · see citing works
Messerli, F. H. (1981) · Archives of Internal Medicine · doi:10.1001/archinte.141.1.81 · Cited by 281 · see citing works
Messerli, F. H. (1981) · Archives of Internal Medicine · doi:10.1001/archinte.1981.00340010073016 · Cited by 210 · see citing works
Gorzelniak, K., Engeli, S., Janke, J., Luft, F. C., & Sharma, A. M. (2002) · Journal of Hypertension · doi:10.1097/00004872-200205000-00032 · Cited by 206 · see citing works
Self-citationHedblad, B., Nilsson, P. M., Engström, G., Berglund, G., & Janzon, L. (2002) · Diabetic Medicine · doi:10.1046/j.1464-5491.2002.00719.x · Cited by 204 · see citing works
Antihypertensive effect of α- and β-adrenergic blockade in obese and lean hypertensive subjects
Wofford, M. (2001) · American Journal of Hypertension · doi:10.1016/s0895-7061(01)01293-6 · Cited by 184 · see citing works
Sjöström, C. D., Peltonen, M., & Sjöström, L. (2001) · Obesity Research · doi:10.1038/oby.2001.20 · Cited by 144 · see citing works
Rocchini, A. P. (2002) · American Journal of Hypertension · doi:10.1016/s0895-7061(01)02299-3 · Cited by 118 · see citing works
Obesity as a determinant for response to antihypertensive treatment.
Schmieder, R. E., GATZKA, C., Schächinger, H., Schobel, H.-P., & Rüddel, H. (1993) · BMJ · doi:10.1136/bmj.307.6903.537 · Cited by 54 · see citing works
Adipose Tissue Metabolism and CD11b Expression on Monocytes in Obese Hypertensives
Boschmann, M., Engeli, S., Adams, F., Gorzelniak, K., Franke, G., Klaua, S., Kreuzberg, U., Luedtke, S., Kettritz, R., Sharma, A. M., et al. (2005) · Hypertension · doi:10.1161/01.hyp.0000171477.63859.b2 · Cited by 45 · see citing works
Self-citationTissue-Specific Response to Interstitial Angiotensin II in Humans
Boschmann, M., Jordan, J., Adams, F., Christensen, N. J., Tank, J., Franke, G., Stoffels, M., Sharma, A. M., Luft, F. C., & Klaus, S. (2003) · Hypertension · doi:10.1161/01.hyp.0000042665.85720.a0 · Cited by 36 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of Sympathetic Activation in Obesity-Related Hypertension
Esler, M., Straznicky, N., Eikelis, N., Masuo, K., Lambert, G., & Lambert, E. (2006) · Hypertension · doi:10.1161/01.hyp.0000242642.42177.49 · Cited by 443 · see citing works
Pépin, J.-L., Tamisier, R., Barone-Rochette, G., Launois, S. H., Lévy, P., & Baguet, J.-P. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200912-1803oc · Cited by 232 · see citing works
Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications
Kalil, G. Z., & Haynes, W. G. (2011) · Hypertension Research · doi:10.1038/hr.2011.173 · Cited by 228 · see citing works
Left ventricular hypertrophy and arterial wall thickening in children with essential hypertension
Litwin, M., Niemirska, A., Śladowska, J., Antoniewicz, J., Daszkowska, J., Wierzbicka, A., Wawer, Z. T., & Grenda, R. (2006) · Pediatric Nephrology · doi:10.1007/s00467-006-0068-8 · Cited by 199 · see citing works
Georgescu, E. F., Ionescu, R. I., Niculescu, M. D., Mogoantă, L., & Vancica, L. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.942 · Cited by 178 · see citing works
“for valsartan, again in contrast with Ichikawa, but in accordance with larger studies [35, 36 ]”
ResultDirect Renin Inhibition With Aliskiren in Obese Patients With Arterial Hypertension
Jordan, J., Engeli, S., Boye, S. W., Breton, S. L., & Keefe, D. L. (2007) · Hypertension · doi:10.1161/hypertensionaha.106.084301 · Cited by 158 · see citing works
“[ 8 ] The observation that treatment with HCTZ (25 mg) alone for 12 weeks achieved BP control in only one third of obese patients with hypertension is similar to the control rate of 43% observed with 12.5 to 50 mg of HCTZ daily in the Treatment in Obese Patients With Hypertension Study.”
BackgroundResultInfluentialSelf-citationObesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis
Rahmouni, K. (2014) · Hypertension · doi:10.1161/hypertensionaha.114.00920 · Cited by 150 · see citing works
Sharma, A. M., Davidson, J. A., Koval, S. E., & Lacourcière, Y. (2007) · Cardiovascular Diabetology · doi:10.1186/1475-2840-6-28 · Cited by 63 · see citing works
“This has already been shown with valsartan and irbesartan, both in combination with HCTZ [17,18].”
BackgroundSelf-citationIchikawa, Y. (2007) · Internal Medicine · doi:10.2169/internalmedicine.46.7173 · Cited by 59 · see citing works
Sharma, A. M., & Engeli, S. (2006) · Journal of the CardioMetabolic Syndrome · doi:10.1111/j.0197-3118.2006.05422.x · Cited by 53 · see citing works
Self-citationJiang, P., Ma, D., Wang, X., Wang, Y., Bi, Y., Jl, Y., Wang, X., & Li, X. (2018) · PubMed Central · doi:10.14348/molcells.2018.2156 · Cited by 54 · see citing works
“Furthermore, despite the use of β-blockers to treat hypertension through the inhibition of sympathetic excitation, metabolic complications caused by β-blockers cannot be ignored (Jordan et al., 2005).”
BackgroundSchmieder, R. E., Philipp, T., Guerediaga, J., Gorostidi, M., Bush, C. A., & Keefe, D. L. (2009) · Journal of Hypertension · doi:10.1097/hjh.0b013e32832be593 · Cited by 49 · see citing works
Role of the Renin–Angiotensin– Aldosterone System in the Metabolic Syndrome
Engeli, S. (2006) · KARGER eBooks · doi:10.1159/000095324 · Cited by 40 · see citing works
Self-citationEuropean Society of Hypertension Working Group on Obesity: background, aims and perspectives
Jordan, J., Engeli, S., Redón, J., Sharma, A. M., Luft, F. C., Narkiewicz, K., & Grassi, G. M. (2007) · Journal of Hypertension · doi:10.1097/hjh.0b013e328051b510 · Cited by 39 · see citing works
Self-citationCzernichow, S., Ninomiya, T., Huxley, R., Kengne, A. P., Batty, G. D., Grobbee, D. E., Woodward, M., Neal, B. C., & Chalmers, J. P. (2010) · Hypertension · doi:10.1161/hypertensionaha.109.140624 · Cited by 38 · see citing works
Prolonged treatment with angiotensin 1–7 improves endothelial function in diet-induced obesity
Beyer, A. M., Guo, D.-F., & Rahmouni, K. (2013) · Journal of Hypertension · doi:10.1097/hjh.0b013e32835ecbe5 · Cited by 37 · see citing works
“Moreover, in clinical trials, agents that are RAS blockers such as Ang type 1 receptor antagonists or ACE inhibitors were found to have favorable effects on the cardiovascular risk factors associated with obesity [37-39] .”
BackgroundLeung, P. S., & de Gasparo, M. (2006) · Journal of the CardioMetabolic Syndrome · doi:10.1111/j.1559-4564.2006.05460.x · Cited by 28 · see citing works
Should We Target the Sympathetic Nervous System in the Treatment of Obesity-Associated Hypertension?
Biaggioni, I. (2007) · Hypertension · doi:10.1161/hypertensionaha.107.090514 · Cited by 27 · see citing works
mTOR and regulation of energy homeostasis in humans
Mannaa, M., Krämer, S., Boschmann, M., & Gollasch, M. (2013) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1057-6 · Cited by 25 · see citing works
“Treatment of obese hypertensive patients with an angiotensin type-1 receptor blocker improved insulin sensitivity [89].”
BackgroundSelf-citationLitwin, M., Śladowska, J., Syczewska, M., Niemirska, A., Daszkowska, J., Antoniewicz, J., Wierzbicka, A., & Wawer, Z. T. (2008) · Pediatric Nephrology · doi:10.1007/s00467-007-0739-0 · Cited by 21 · see citing works
Furukawa, H., Mawatari, K., Koyama, K., Yasui, S., Morizumi, R., Shimohata, T., Harada, N., Takahashi, A., & Nakaya, Y. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.04.008 · Cited by 21 · see citing works
“…trials have demonstrated that angiotensin II receptor blockers can substantially lower the risk of type 2 diabetes and may protect cardiac and renal function compared with other antihypertensive drugs such as β-blockers and calcium channel blockers (Jordan et al., 2005; Morimoto et al., 2006).”
BackgroundThe Efficacy and Safety of Valsartan in Obese and Non-Obese Pediatric Hypertensive Patients
Meyers, K. E. C., Lieberman, K. V., Solar‐Yohay, S., Han, G., & Shi, V. C. (2011) · Journal of Clinical Hypertension · doi:10.1111/j.1751-7176.2011.00502.x · Cited by 18 · see citing works
Drug Mechanisms to Help in Managing Resistant Hypertension in Obesity
Jansen, P. M., Danser, J., Spiering, W., & van den Meiracker, A. H. (2010) · Current Hypertension Reports · doi:10.1007/s11906-010-0123-5 · Cited by 17 · see citing works
“) In a third study the effects of valsartan, 160 mg daily, were compared with those of atenolol, 100 mg daily, in a double-blind, parallel-group study that included 132 patients with an average BMI of 33 kg/m(2) and a waist circumference of 110 cm [37].”
BackgroundThe Role of Sympatho-Inhibition in Combination Treatment of Obesity-Related Hypertension
Carnagarin, R., Gregory, C., Azzam, O., Hillis, G. S., Schultz, C. J., Watts, G. F., Bell, D. A., Matthews, V. B., & Schlaich, M. P. (2017) · Current Hypertension Reports · doi:10.1007/s11906-017-0795-1 · Cited by 17 · see citing works
“line drug for antihypertensive treatment of obese patients [42].”
Pharmacotherapeutic strategies for treating hypertension in patients with obesity
Carnagarin, R., Matthews, V. B., Gregory, C., & Schlaich, M. P. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1458092 · Cited by 17 · see citing works
Treatment of Arterial Hypertension in Obese Patients
Wenzel, U. O., Benndorf, R. A., & Lange, S. (2013) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2012.12.009 · Cited by 16 · see citing works
Hershon, K. S. (2011) · Endocrine Practice · doi:10.4158/ep10106.ra · Cited by 15 · see citing works
Cataldi, M., Geronimo, O. D., Trio, R., Scotti, A., Memoli, A., Capone, D., & Guida, B. (2016) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-016-0055-z · Cited by 13 · see citing works
“Specifically, a few studies showed that drugs acting on RAA system and, in particular, ARBs could improve metabolic status in patients with metabolic syndrome [32], decreasing visceral fat accumulation [33] and improving insulin sensitivity and lipid profile [34], whereas visceral adiposity increases the risk of devel…”
BackgroundValsartan/hydrochlorothiazide: pharmacology and clinical efficacy
Kondrack, R., & Mohiuddin, S. (2009) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425250903136730 · Cited by 12 · see citing works
“In addition to its use in the general population, valsartan/HCTZ has also been studied in special patient sub-groups such as patients who are overweight, obese, diabetic, elderly, black and those that have cardiovascular risk factors (Table 4) [27,40-43].”
BackgroundBlood pressure responder rates versus goal rates: which metric matters?
Basile, J. (2009) · Therapeutic Advances in Cardiovascular Disease · doi:10.1177/1753944708101552 · Cited by 9 · see citing works
“…et al. 2007; Hosohata et al. 2007; Mochizuki et al. 2007; Saito et al. 2007; Agrawal et al. 2006; Black et al. 2006; 160 http://tac.sagepub.com Jordan et al. 2005; Mourad et al. 2004; Black et al. 2003; Eguchi et al. 2003; Gil-Extremera et al. 2003; Grassi et al. 2003; Pepine et al. 2003a;…”
BackgroundResultInfluentialDohi, T., Narui, K., Kasai, T., Takaya, H., Inoshita, A., Maeno, K.-I., Kasagi, S., Ishiwata, S., Ohno, M., Yamaguchi, T., et al. (2011) · Heart and Vessels · doi:10.1007/s00380-010-0104-2 · Cited by 9 · see citing works
“By contrast, large-scale clinical trials have reported a significantly greater antihypertensive effect in hypertensive patients treated with an ARB compared with those taking beta-blockers [12, 13].”
ResultOparil, S., Abate, N. I., Chen, E., Creager, M. A., Galet, V. A., Jia, G., Julius, S., Lerman, A., Lyle, P. A., Pool, J. L., et al. (2008) · Current Medical Research and Opinion · doi:10.1185/030079908x280716 · Cited by 9 · see citing works
Karagiannis, A. I., Mikhailidis, D. P., Kakafika, A. I., Τζιόμαλος, Κ., & Athyros, V. G. (2006) · Current Pharmaceutical Design · doi:10.2174/138161207779313713 · Cited by 8 · see citing works
“Moreover, atenolol treatment in obese hypertensive patients who are particularly susceptible to the development of diabetes had less beneficial effect on insulin resistance than treatment with valsartan [88].”
BackgroundAntihypertensive therapy in the obese hypertensive patient
Chrostowska, M., Szczęch, R., & Narkiewicz, K. (2006) · Current Opinion in Nephrology & Hypertension · doi:10.1097/01.mnh.0000242173.14082.dc · Cited by 8 · see citing works
Mende, C. W., Giles, T. D., Bharucha, D. B., Ferguson, W., Mallick, M., & Patel, M. (2017) · Journal of Clinical Hypertension · doi:10.1111/jch.12965 · Cited by 7 · see citing works
Blood pressure and cardiorenal responses to antihypertensive therapy in obese women
Rosa, E. C., Zanella, M. T., Kohlmann, N. E. B., Ferreira, S. R. G., Plavnik, F. L., Ribeiro, A. B., & Kohlmann, O. (2008) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302008000100010 · Cited by 4 · see citing works
Treatment of hypertension associated with prediabetes
Barna, I. (2009) · Orvosi Hetilap · doi:10.1556/oh.2009.28619 · Cited by 2 · see citing works
Putnam, K. (2012) · UKnowledge (University of Kentucky) · Cited by 1 · see citing works
Kızılırmak, P., ÖZDEMİR, O., YILDIZ, O. B., & Üresin, Y. (2015) · Turkiye Klinikleri Journal of Endocrinology · doi:10.5336/endocrin.2014-39666
Tomonaga, O., & Iwamoto, Y. (2010) · Diabetology International · doi:10.1007/s13340-010-0012-9
Ismael, N. S. (2011) · Indian Journal Of Applied Research · doi:10.15373/2249555x/jan2014/140
- Authors
- Jordan, J., Engeli, S., Boschmann, M., Weidinger, G., Luft, F. C., Sharma, A. M., & Kreuzberg, U.
- Affiliations
- Helios Kliniken (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Novartis (Germany) (DE)
- Hamilton General Hospital (CA)
- Corresponding author
- Jordan, Jens
- Venue
- Journal of Hypertension
- Published
- 2005-12
- Volume
- 23
- Issue
- 12
- Pages
- 2313-2318
- ISSN
- 0263-6352 (ISSN-L)
- OpenAlex
- W2045285495
- Cited by
- 41
- References
- 21
- Citations by year
- 2018: 2 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- valsartan, atenolol, essential hypertension, obesity, blood pressure reduction, insulin resistance, HOMA-IR, glucose metabolism, lipid metabolism, C-reactive protein, hydrochlorothiazide, angiotensin receptor blockers, antihypertensive therapy, body weight, low-dose diuretics, metabolic side effects
- MeSH terms
- Valsartan, Adrenergic beta-Antagonists, Adult, Aged, Antihypertensive Agents, Atenolol, Blood Glucose, Blood Pressure, Double-Blind Method, Female, Humans, Hydrochlorothiazide, Hypertension, Lipids, Male, Middle Aged, Obesity, Tetrazoles, Valine, Angiotensin II Type 1 Receptor Blockers, Sodium Chloride Symporter Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
