Hypertension in Metabolic Syndrome: Novel Insights

Author(s): Alexandra Katsimardou, Konstantinos Imprialos, Konstantinos Stavropoulos, Alexandros Sachinidis, Michalis Doumas, Vasilios Athyros*.

Journal Name: Current Hypertension Reviews

Volume 16 , Issue 1 , 2020

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Graphical Abstract:


Background: Metabolic syndrome (MetS) is characterized by the simultaneous presence of obesity, hypertension, dyslipidemia and hyperglycemia in an individual, leading to increased cardiovascular disease (CVD) risk. It affects almost 35% of the US adult population, while its prevalence increases with age. Elevated blood pressure is the most frequent component of the syndrome; however, until now, the optimal antihypertensive regiment has not been defined.

Objective: The purpose of this review is to present the proposed definitions for the metabolic syndrome, as well as the prevalence of hypertension in this condition. Moreover, evidence regarding the metabolic properties of the different antihypertensive drug classes and their effect on MetS will be displayed.

Methods: A comprehensive review of the literature was performed to identify data from clinical studies for the prevalence, pathophysiology and treatment of hypertension in the metabolic syndrome.

Results: Hypertension is present in almost 80% of patients with metabolic syndrome. The use of thiazide diuretics and b-blockers has been discouraged in this population; however, new evidence suggests their use under specific conditions. Calcium channel blockers seem to exert a neutral effect on MetS, while renin-angiotensin system inhibitors are believed to be of the most benefit, although differences exist between the different agents of this category.

Conclusion: Controversy still exists regarding the optimal antihypertensive treatment for hypertension in MetS. Due to the high prevalence of hypertension in this population, more data from clinical trials are needed in the future.

Keywords: Hypertension, metabolic syndrome, thiazide diuretics, b-blockers, calcium channel blockers, renin-angiotensin system inhibitors, ACE-inhibitors, angiotensin receptor blockers.

Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-607.
Organization WH. Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO consultation Part 1, Diagnosis and classification of diabetes mellitus. Geneva: World health organization 1999.
Daskalopoulou SS, Athyros VG, Kolovou GD, et al. Definitions of metabolic syndrome: Where are we now? Curr Vasc Pharmacol 2006; 4: 185-97.
Athyros VG, Ganotakis ES, Tziomalos K, et al. Comparison of four definitions of the metabolic syndrome in a Greek (Mediterranean) population. Curr Med Res Opin 2010; 26: 713-9.
Aguilar M, Bhuket T, Torres S, et al. Prevalence of the metabolic syndrome in the United States, 2003-2012. J Am Med Assoc 2015; 313: 1973.
Arcucci O, de Simone G, Izzo R, et al. Association of suboptimal blood pressure control with body size and metabolic abnormalities. J Hypertens 2007; 25: 2296-300.
Expert Panel on Detection. Evaluation and T of HBC in A. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). J Am Med Assoc 2001; 285: 2486-97.
Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome an American Heart Association/national heart, lung, and blood institute scientific statement. Circulation 2005; 112: 2735-52.
International Diabetes Federation; The IDF consensus worldwide definition of the Metabolic Syndrome Avilable at: https://www. idf.org/e-library/consensus-statements/60-idfconsensus-worldwide-definitionof-the-metabolic-syndrome.html(2006) .Accessed 18 October 2018). .
Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: A joint interim statement of the international diabetes federation task force on epidemiology and prevention; National heart, lung, and blood institute; American heart association; World heart federation; International. Circulation 2009; 120: 1640-5.
Simmons RK, Alberti KG, Gale EA, et al. The metabolic syndrome: Useful concept or clinical tool? Report of a WHO expert consultation. Diabetologia 2010; 53: 600-5.
Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk: A systematic review and meta-analysis. J Am Coll Cardiol 2010; 56: 1113-32.
Athyros VG, Ganotakis E, Kolovou GD, et al. Assessing the treatment effect in metabolic syndrome without perceptible diabetes (ATTEMPT): A prospective-randomized study in middle aged men and women. Curr Vasc Pharmacol 2011; 9: 647-57.
Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003; 37: 917-23.
Choi HK, Ford ES, Li C, et al. Prevalence of the metabolic syndrome in patients with gout: The Third National Health and Nutrition Examination Survey. Arthritis Care Res 2007; 57: 109-15.
Esposito K, Chiodini P, Colao A, et al. Metabolic syndrome and risk of cancer: A systematic review and meta-analysis. Diabetes Care 2012; 35: 2402-11.
Katsiki N, Athyros V, Karagiannis A, et al. Characteristics other than the diagnostic criteria associated with metabolic syndrome: An overview. Curr Vasc Pharmacol 2014; 12: 627-41.
Athyros VG, Karagiannis A, Ganotakis ES, et al. Association between the changes in renal function and serum uric acid levels during multifactorial intervention and clinical outcome in patients with metabolic syndrome. A post hoc analysis of the ATTEMPT study. Curr Med Res Opin 2011; 27: 1659-68.
Athyros VG, Ferlita A, Tziomalos K, et al. Treating arterial stiffness associated with features of metabolic syndrome not included in its diagnostic criteria: Cutting off the heads of lernaean hydra, keeper of the underworld. Open Hypertens J 2013; 5: 67-74.
Katsiki N, Athyros VG, Karagiannis A, et al. Metabolic syndrome and non-cardiac vascular diseases: an update from human studies. Curr Pharm Des 2014; 20: 4944-52.
Athyros VG, Giouleme O, Ganotakis ES, et al. Safety and impact on cardiovascular events of long-term multifactorial treatment in patients with metabolic syndrome and abnormal liver function tests: A post hoc analysis of the randomised ATTEMPT study. Arch Med Sci 2011; 7: 796-805.
Chimonas T, Karagiannis A, Athyros VG, et al. Blood pressure levels constitute the most important determinant of the metabolic syndrome in a mediterranean population: A discrimination analysis. Metab Syndr Relat Disord 2010; 8: 523-9.
Mancia G, Bombelli M, Corrao G, et al. Metabolic syndrome in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study: Daily life blood pressure, cardiac damage, and prognosis. Hypertension 2007; 49: 40-7.
Schillaci G, Pirro M, Vaudo G, et al. Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol 2004; 43: 1817-22.
Pannier B, Thomas F, Bean K, et al. The metabolic syndrome: Similar deleterious impact on all-cause mortality in hypertensive and normotensive subjects. J Hypertens 2008; 26: 1223-8.
Cuspidi C, Facchetti R, Bombelli M, et al. Risk of new-onset metabolic syndrome associated with white-coat and masked hypertension: Data from a general population. J Hypertens 2018; 36: 1833-9.
Kjeldsen SE, Naditch-Brule L, Perlini S, et al. Increased prevalence of metabolic syndrome in uncontrolled hypertension across Europe: The global cardiometabolic risk profile in patients with hypertension disease survey. J Hypertens 2008; 26: 2064-70.
Cuspidi C, Meani S, Fusi V, et al. Metabolic syndrome and target organ damage in untreated essential hypertensives. J Hypertens 2004; 22: 1991-8.
Leoncini G, Ratto E, Viazzi F, et al. Metabolic syndrome is associated with early signs of organ damage in nondiabetic, hypertensive patients. J Intern Med 2005; 257: 454-60.
Mulè G, Nardi E, Cottone S, et al. Influence of metabolic syndrome on hypertension-related target organ damage. J Intern Med 2005; 257: 503-13.
Athyros VG, Mikhailidis DP. High incidence of metabolic syndrome further increases cardiovascular risk in patients with type 2 diabetes. Implications for everyday practice. J Diabetes Complications 2016; 30: 9-11.
Kotsis V, Jordan J, Micic D, et al. Obesity and cardiovascular risk: A call for action from the european society of hypertension working group of obesity, diabetes and the high-risk patient and european association for the study of obesity: part A: mechanisms of obesity induced hypertension. J Hypertens 2018; 36: 1427-40.
Mancia G, Bousquet P, Elghozi JL, et al. The sympathetic nervous system and the metabolic syndrome. J Hypertens 2007; 25: 909-20.
Nickenig G, Röling J, Strehlow K, et al. Insulin induces upregulation of vascular receptor gene expression by posttranscriptional mechanisms. Circulation 1998; 98: 2453-60.
Andronico G, Mangano M, Ferrara L, et al. In vivo relationship between insulin and endothelin role of insulin-resistance. J Hum Hypertens 1997; 11: 63.
Tziomalos K, Athyros VG, Karagiannis A, et al. Endothelial dysfunction in metabolic syndrome: Prevalence, pathogenesis and management. Nutr Metab Cardiovasc Dis 2010; 20: 140-6.
Schlaich M, Straznicky N, Lambert E, et al. Metabolic syndrome: A sympathetic disease? Lancet Diabetes Endocrinol 2015; 3: 148-58.
Kotsis V, Stabouli S, Papakatsika S, et al. Mechanisms of obesity-induced hypertension. Hypertens Res 2010; 33: 386-93.
Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: A report of the american college of cardiology/american heart association task force on clinical pr. J Am Coll Cardiol 2018; 71: e127-248.
Williams B, Mancia G, Spiering W, et al. 2018 ESC / ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension. J Hypertens 2018; 36: 1953-2041.
Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA 2003; 289: 2560-71.
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA 2002; 288: 2981-97.
Reisin E, Graves JW, Yamal JM, et al. Blood pressure control and cardiovascular outcomes in normal-weight, overweight, and obese hypertensive patients treated with three different antihypertensives in ALLHAT. J Hypertens 2014; 32: 1503-13.
Amery A, Bulpitt C, Schaepdryver AD, et al. Glucose intolerance during diuretic therapy: Results of trial by the European working party on hypertension in the elderly. Lancet 1978; 311: 681-3.
Hoskins B, Jackson CM. The mechanism of chlorothiazide-induced carbohydrate intolerance. J Pharmacol Exp Ther 1978. 206: 423 LP-430.
Mancia G, Grassi G, Zanchetti A. New-onset diabetes and antihypertensive drugs. J Hypertens 2006; 24: 3-10.
Barzilay JI, Davis BR, Cutler JA, et al. Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment: A report from the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). Arch Intern Med 2006; 166: 2191-201.
Black HR, Davis B, Barzilay J, et al. Metabolic and clinical outcomes in nondiabetic individuals with the metabolic syndrome assigned to chlorthalidone, amlodipine, or lisinopril as initial treatment for hypertension. Diabetes Care 2008; 31 (353 LP-360. )
Mancia G, Brown M, Castaigne A, et al. Outcomes with nifedipine GITS or Co-amilozide in hypertensive diabetics and nondiabetics in intervention as a goal in hypertension (INSIGHT). Hypertension 2003; 41: 431-6.
Handberg EM, Cooper-dehoff RM, Marks RG, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil–Trandolapril Study (INVEST): A randomized controlled trial. JAMA 2003; 290: 2805-16.
Gress TW, Nieto FJ, Shahar E, et al. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. N Engl J Med 2000; 342: 905-12.
Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: A network meta-analysis. Lancet 2007; 369: 201-7.
Aksnes TA, Kjeldsen SE, Rostrup M, et al. Impact of new-onset diabetes mellitus on cardiac outcomes in the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial population. Hypertension 2007; 50: 467-73.
Verdecchia P, Reboldi G, Angeli F, et al. Adverse prognostic significance of new diabetes in treated hypertensive subjects. Hypertension 2004; 43: 963-9.
Kostis JB, Wilson AC, Freudenberger RS, et al. Long-term effect of diuretic-based therapy on fatal outcomes in subjects with isolated systolic hypertension with and without diabetes. Am J Cardiol 2005; 95: 29-35.
Zillich AJ, Garg J, Basu S, et al. Thiazide diuretics, potassium, and the development of diabetes: A quantitative review. Hypertension 2006; 48: 219-24.
Lambert GW, Straznicky NE, Lambert EA, et al. Sympathetic nervous activation in obesity and the metabolic syndrome-Causes, consequences and therapeutic implications. Pharmacol Ther 2010; 126: 159-72.
Sharma AM, Pischon T, Hardt S, et al. Hypothesis: ß-adrenergic receptor blockers and weight gain: A systematic analysis. Hypertension 2001; 37: 250-4.
Dahlöf B, Devereux RB, Kjeldsen SE, et al. 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.
Gupta AK, Dahlof B, Dobson J, Sever PS, Wedel H. Determinants of new-onset diabetes randomized in the anglo-scandinavian cardiac outcomes trial – blood pressure lowering arm and the relative influence of antihypertensive medication. Diabetes Care 2008; 31: 982-8.
The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). 2013 ESH/ESC Guidelines for the management of arterial hypertension. Eur Heart J 2013; 34: 2159-219.
Bakris GL, Fonseca V, Katholi RE, et al. Differential effects of β-blockers on albuminuria in patients with type 2 diabetes. Hypertension 2005; 46: 1309-15.
Bell DSH, Bakris GL, McGill JB. Comparison of carvedilol and metoprolol on serum lipid concentration in diabetic hypertensive patients. Diabetes Obes Metab 2005; 11: 234-8.
Bakris GL, Fonseca V, Katholi RE, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: A randomized controlled trial. J Am Med Assoc 2004; 292: 2227-36.
Fonseca VA. Effects of b-blockers on glucose and lipid metabolism. Curr Med Res Opin 2010; 26: 615-29.
Schmidt AC, Graf C, Brixius K, et al. Blood pressure-lowering effect of nebivolol in hypertensive patients with type 2 diabetes mellitus: The YESTONO study. Clin Drug Investig 2007; 27: 841-9.
Celik T, Iyisoy A, Kursaklioglu H, et al. Comparative effects of nebivolol and metoprolol on oxidative stress, insulin resistance, plasma adiponectin and soluble P-selectin levels in hypertensive patients. J Hypertens 2006; 24: 591-6.
Martinez-Martin FJ, Rodriguez-Rosas H, Peiro-Martinez I, et al. Olmesartan/amlodipine vs olmesartan/hydrochlorothiazide in hypertensive patients with metabolic syndrome: The OLAS study. J Hum Hypertens 2011; 25: 346-53.
Zanchetti A, Hennig M, Baurecht H, et al. Prevalence and incidence of the metabolic syndrome in the European Lacidipine Study on Atherosclerosis (ELSA) and its relation with carotid intima–media thickness. J Hypertens 2007; 25: 2463-70.
Henriksen EJ, Prasannarong M. Molecular and cellular endocrinology the role of the renin-angiotensin system in the development of insulin resistance in skeletal muscle. Mol Cell Endocrinol 2013; 378: 15-22.
Karagiannis A, Mikhailidis DP, Athyros VG, et al. The role of renin – angiotensin system inhibition in the treatment of hypertension in metabolic syndrome : Are all the angiotensin receptor blockers equal? Expert Opin Ther Targets 2007; 11: 191-205.
Zreikat HH, Harpe SE, Slattum PW, et al. Effect of renin-angiotensin system inhibition on cardiovascular events in older hypertensive patients with metabolic syndrome. Metabolism 2014; 63: 392-9.
Kintscher U, Bramlage P, Paar WD, et al. Irbesartan for the treatment of hypertension in patients with the metabolic syndrome : A sub analysis of the Treat to Target post authorization survey. Prospective observational, two armed study. Cardiovasc Diabetol 2007; 11: 1-11.
Takagi H, Niwa M, Mizuno Y, et al. Telmisartan as a metabolic sartan: The first meta-analysis of randomized controlled trials in metabolic syndrome. J Am Soc Hypertens 2013; 7: 229-35.
Wang Y, Qiao S, Han D, et al. Telmisartan improves insulin resistance: A meta-analysis. Am J Ther 2018; 10: 1-10.

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Year: 2020
Page: [12 - 18]
Pages: 7
DOI: 10.2174/1573402115666190415161813

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