7mo. Congreso Virtual de Cardiología - 7th. Virtual Congress of Cardiology

Index > 7VCC > High Blood Pressure

Metabolic Syndrome in Hypertension. Treatment Challenges and Goals

Alejandro De La Sierra Department of Internal Medicine. Hospital Mutua Terrassa. University of Barcelona. Barcelona, Spain.

Abstract Changes in lifestyle in the developed world are promoting the epidemic growth of overweight and obesity, leading to several metabolic abnormalities (lipids, glucose and blood pressure), and increasing the future risk of type 2 diabetes, cardiovascular events and death. Metabolic syndrome represents the combination of abdominal obesity, insulin resistance, atherogenic dyslipidemia, and prothrombotic and proinflammatory states. Although some controversies in the pathogenesis and clinical importance of metabolic syndrome still remain, the development of useful clinical tools to identify these patients more easily has derived to an increased recognition in the adult population. Management of patients with metabolic syndrome is a clinical challenge and requires a multifactorial, multidisciplinary approach. Changes in lifestyle are obviously the first therapeutic step and include both dietary modifications and increased daily exercise. Several questions remain to be elucidated with respect to pharmacological treatment. The blood pressure levels required to initiate antihypertensive treatment, the blood pressure goal to be achieved and the possibility of including a renin-angiotensin system blocker as a part of the pharmacological treatment are still under discussion. Moreover, there is lack or poor evidence on the need for specific drugs to reduce triglycerides, to increase HDL-cholesterol, to improve insulin sensitivity or to decrease abdominal obesity. Independently, it is generally accepted that earlier and more aggressive therapy in subjects with metabolic syndrome will result in a decrease of the future cardiovascular morbidity and mortality worldwide. Keywords: Cardiometabolic risk, metabolic syndrome, hypertension, antihypertensive agents, type 2 diabetes.

The concepts of metabolic syndrome and cardiometabolic risk Cardiometabolic risk represents a situation where the possibilities of developing atherosclerotic cardiovascular disease and diabetes mellitus are significantly enhanced as a consequence of the presence of insulin resistance and atherogenic dyslipidemia, this latter characterized by the presence of low HDL-cholesterol and high triglyceride levels[1,2]. The clinical diagnosis of this situation is made through the finding of an enhanced waist circumference (above 102 cm in males and 88 cm in females) accompanied by the above quoted alterations in lipid profile (HDL-cholesterol below 40 mg/dl in males and 50 mg/dl in females and serum triglycerides above 150 mg/dl). Cardiometabolic risk is particularly prevalent in patients diagnosed as having metabolic syndrome (MS), which in turn requires for a correct diagnosis besides an increased waist circumference, a low HDL-cholesterol and elevated triglycerides, the potential presence of blood pressure (BP) values above 130/85 mmHg and a fasting serum glucose above 100 mg/dl [3,4]. The International Diabetes Federation has also defined the MS in Europids by the presence of a waist circumference above 94 cm in males and 80 in females accompanied by the finding of two out of the other four criteria that remain unchanged as compared to the ATP-III definition [5]. Recently, a consensus document [6] signed by the International Diabetes Federation, the National Heart, Lung, and Blood Institute, the American Heart Association, the World Heart Federation, the International Atherosclerosis Society and the International Association for the Study of Obesity has been released, harmonizing these different criteria definition of metabolic syndrome. The document does not consider obesity as a prerequisite for the definition (as stated in the IDF criteria) and maintain the possibility of all 3-factor combinations among the 5 possible alterations. This is in agreement with the previous reports from NCEP/ATP III [3] and NHLBI/AHA [4], with the exception of the definition of elevated waist circumference, with different thresholds depending on ethnicities. For people of Caucasian origin, including Europids, the level of waist circumference above 94 cm in men and 80 cm in women must be considered as increased risk, although the threshold of the waist circumference above 102 cm in men and 88 cm in women, defines the level at which the risk is substantially higher and probably must be considered as the definition criteria of abdominal obesity.

¿How frequent and relevant is the metabolic syndrome in the hypertensive population? The prevalence of MS in the hypertensive population is very high. In a study with more than 19000 hypertensive patients attended in primary care centres in Spain, MS was present in more than 40% of subjects, by using the original ATP III definition [3] and increased until 60% when the IDF criteria [5] was applied [7]. Metabolic syndrome and consequently increased cardiometabolic risk are then very prevalent in the hypertensive population and need to be incorporated to a correct stratification of risk that has to be done in every hypertensive patient. In fact, the Guidelines of the European Society of Hypertension- European Society of Cardiology [8,9] consider the concomitant finding of arterial hypertension and MS syndrome as a situation of high-added cardiovascular risk. The reason to do this is based on two facts. Firstly, metabolic syndrome and the accompanying cardiometabolic risk result in a significant increment in

7mo. Congreso Virtual de Cardiología - 7th. Virtual Congress of Cardiology

cardiovascular morbidity and mortality in several population-based studies, as previously reviewed[10], as well as in hypertensive patients[11]. Secondly, the presence of metabolic syndrome is accompanied by a 3-6 times increase in risk of developing type 2 diabetes[12]. On the other hand the presence of MS is accompanied by a significant enhancement in the risk of developing chronic kidney disease (albuminuria and/or a diminished estimated glomerular filtration rate). The higher the number of components used for the definition of metabolic syndrome the higher will be the prevalence of either microalbuminuria and/or an estimated GFR value < 60 ml/min/1.73 m2 [13].

¿How relevant is the development of diabetes mellitus in a hypertensive population? The development of new onset diabetes and its relevance in hypertensives has been widely considered [14,15]. The type of antihypertensive therapy used, alone or in combinations, is relevant to accelerate the appearance of diabetes. A network meta-analysis [16] has shown that the best protection is obtained when angiotensin receptor blockers and converting enzyme inhibitors are used, while diuretics and betablockers are occupying the last position in particular when used in combination. Albeit some authors have denied that the development of new onset diabetes contributes to worsen the short-term prognosis of hypertensive patients according to the data of studies like SHEP[17] and ALLHAT[18], it seems clear that becoming a diabetic must be relevant for the long-term patient’s prognosis. In fact, it has been shown that with 2 and a half years of follow-up above that in ALLHAT the risk of new diabetics was equal to that of patients entering the study as declared diabetics[19].

¿How should a patient with hypertension and metabolic syndrome be treated? The aim of intervention in patients with MS and high cardiometabolic risk is to achieve an optimal reduction of such risk. Lifestyle modifications counteract the effect of the underlying risk factors (obesity, physical inactivity and atherogenic diet). Moreover, hypertensives also require a tight BP control, a choice of antihypertensive treatment not producing other metabolic disturbances, and quite often parallel drug treatment for associated metabolic risk factors (dyslipidemia, insulin resistance and prothrombotic and proinflammatory states).

Lifestyle interventions They are obviously the first step in achieving the goal of cardiometabolic risk reduction. The key lifestyle interventions are the promotion of exercise and energy expenditure and the reduction of overweight by caloric restriction[20]. The minimal requirements for long-term effectiveness include caloric restriction in the range of 500-1000 Kcal with a 7%-10% weight loss in 12 months and regular aerobic exercise of 30-45 minutes daily. Whereas extreme caloric-restricted or element dissociated diets have no long-term advantages, more intensive exercise programs have additional cardiovascular benefits and help to maintain weight loss. Lifestyle interventions have clearly beneficial effects on BP and the lipid profile and reduce the incidence of new-onset diabetes[19]. Moreover, recent data suggest a long-term effect on the reduction in cardiovascular morbidity [21]. Other lifestyle changes also have a beneficial effect on specific CV risk factors and must be encouraged in specific patients. Lowering salt intake and alcohol consumption have moderate BP lowering effects, which are enhanced in conjunction with weight loss and increased exercise[8]. In addition, a diet rich in fruits, vegetables and low-fat dairy products (DASH diet) substantially lowers BP in comparison to the standard American diet[23]. Also the Mediterranean diet, which is equally rich in fruits, vegetables, fish and olive oil, has a favourable impact on atherogenic dyslipidemia in MS patients[24]. Maintenance of lifestyle changes requires counselling and may prove difficult in the long term. For this reason, pharmacological treatment of BP, dyslipidemia, insulin resistance and obesity will be required for most patients to reduce cardiometabolic risk[25].

Antihypertensive therapy As mentioned above, the European Society of Hypertension / European Society of Cardiology Guidelines[8,9] emphasize the importance of metabolic syndrome as an indicator of high added cardiovascular risk in hypertensives, thus indicating early antihypertensive treatment if lifestyle measures are not enough to reach BP targets. No comparative studies of the different antihypertensive drug classes in hypertensives with metabolic syndrome are available. However, considering the increased risk of developing new-onset diabetes in these subjects, as one of the components of cardiometabolic risk, the choice of antihypertensive treatment must take this additional risk into account. Some international guidelines recommend diuretics as the first-step therapy for hypertensive patients without a compelling indication for other antihypertensive drug classes. However, it has been clearly established that diuretics increase the risk (23%) of new-onset diabetes compared to placebo[16]. Conversely, calcium channel blockers and, especially, reninangiotensin system blockers (angiotensin receptor blockers and angiotensin-converting-enzyme inhibitors) decrease this risk (33% with ACE inhibitors and 43% with angiotensin receptor blockers). These differences are probably even more pronounced in the specific subset of patients with MS. Thus, it seems reasonable that the first consideration in antihypertensive treatment in hypertensives with MS and high cardiometabolic risk should focus on the inhibition of the renin-angiotensin system with either ACE inhibition or angiotensin blockade. Additional evidence can be derived from comparative studies of antihypertensive drugs that have included an important proportion of diabetic subjects, most of them also suffering from MS. In this regard, the Appropriate Blood Pressure Control in Diabetics (ABCD)[26] compared in the subset of hypertensive diabetics, antihypertensive treatment based on the ACE inhibitor enalapril or the calcium channel blocker nisoldipine. The study was prematurely halted due to differences in the number of myocardial infarction that favoured enalapril in comparison to nisoldipine. Hypertensive patients with metabolic syndrome and especially those with type 2 diabetes are often resistant to the effects of

7mo. Congreso Virtual de Cardiología - 7th. Virtual Congress of Cardiology

antihypertensive drugs and may require drug combinations to achieve blood pressure control. Although some studies have demonstrated the benefits of using diuretics in combination with ACE inhibitors [27] or ARBs [28] in diabetics, two comparative studies suggest that combining a renin-angiotensin blocker with a calcium channel blocker could be a better option. The Anglo Scandinavian Cardiac Outcome Trial (ASCOT)[29] compared antihypertensive treatment based on the calcium channel blocker amlodipine with the addition in most patients of the ACE inhibitor perindopril against the betablocker atenolol with the addition of a thiazide diuretic also in the vast majority of patients. The study was also prematurely interrupted due to a consistent benefit of the former therapeutic option. More than 5000 diabetic patients were included in ASCOT and a particular analysis of this cohort revealed that the benefits of the combination of amlodipine and perindopril were maintained in diabetics[30]. Another study, the ACCOMPLISH trial [31] also compared 2 combinations of antihypertensive agents in high-risk hypertensives. Patients were treated with either the combination of the ACE inhibitor benazepril and the calcium channel blocker amlodipine or benazepril combined with hydrocholothiazide. The proportion of diabetics in this study reached 60%. Main results revealed a 20% reduction in the primary endpoint in patients treated with benazepril amlodipine combination. Subgroup analyses did not find heterogeneity of the results in subjects with or without diabetes. No evidence supports a preference for ACE inhibitors or ARB’s in the treatment of MS patients. The ONTARGET [32] trial compared telmisartan with ramipril in patients at risk for cardiovascular events (one third with diabetes) and found no differences in rates of cardiovascular events between groups. It has been hypothesized that the particularity of some angiotensin receptor blockers acting as modulators of the nuclear receptor PPAR-gamma[33] could be important for additional metabolic benefits of these drugs. Comparative studies of telmisartan, the ARB with a more potent ability to stimulate the PPAR-gamma receptor, against losartan[34], irbesartan[35] or eprosartan[36] resulted in better metabolic outcomes, as measured by fasting glucose, insulin and lipids. However, in the ONTARGET trial rates of new onset diabetes were not different in ramipril or telmisartan treated patients[32]. Non-hypertensive patients with metabolic syndrome usually have high-normal BP (systolic 130-139 mmHg and/or diastolic 85-89 mmHg). Specific dietary interventions, such as sodium restriction or the adoption of the DASH diet, in addition to caloric restriction and increased exercise, could be helpful. For patients also having diabetes antihypertensive treatment with renin-angiotensin blockers is able to prevent the development of microalbuminuria in normoalbuminuric patients[37] or overt proteinuria in those having microalbuminuria[38]. For the remaining subjects, no evidence is available for antihypertensive treatment, except that hypertension development is prevented[39]. Other drugs that could add benefit in patients with metabolic syndrome Lipid-lowering therapy The ASCOT Trial demonstrated that treatment with 10 mg atorvastatin was effective in reducing cardiovascular events when hypertension was accompanied by 3 or more additional risk factors, including most that are contained in the definition of metabolic syndrome[40]. However, the typical dyslipidemia in hypertensives with MS is characterized by low-HDL cholesterol and increased triglycerides. Two classes of drugs reduce triglycerides and increase HDL-cholesterol. These are nicotinic acid and fibrates. Although limited evidence is available, some post-hoc analyses suggest a beneficial effect of these drugs in patients with metabolic syndrome[41,42].

Insulin sensitizers In addition to lifestyle changes, treatment with metformin[19], acarbose[43] and thiazolidindiones[44] decreases the risk of new-onset diabetes in patients with impaired glucose tolerance. However, the long-term benefits of these drugs and the cost-benefit analysis have not been adequately addressed.

Antiobesity drugs Abdominal obesity is one the main components of MS and increased cardiometabolic risk. In addition to a restricted caloric diet and increased exercise, several pharmacological approaches have been tested in these patients. Although effective in reducing weight and waist circumference, drugs such as sibutramine or rimonabant withdrew from the market due to unacceptable side effects and only orlistat, an inhibitor of gastrointestinal lipases, especially pancreatic lipase, is available. Orlistat promotes a moderate weight loss and also has a favourable influence on lipids and glycemic control, especially in diabetics, although gastrointestinal tolerance is poor[45]. The need of new pharmacological approaches to abdominal obesity with efficacious, but also safe drugs, is a pharmaceutical urgency.

Antithrombotic drugs A key feature of metabolic syndrome that explains the increased cardiometabolic risk is an enhanced prothrombotic state, especially in the presence of insulin resistance. Postprandial hyperglycemia, increased free fatty acids and elevated triglyceride levels may all have adverse effects on platelets, coagulation and fibrinolysis. Pharmacological interventions targeting these abnormalities have the potential to reduce thrombosis. Antiplatelet drugs such as low-dose aspirin have proven benefit in patients with previous CV disease, but extension to other groups, including diabetics is controversial[46]. Efforts to control BP should be reinforced before the introduction of aspirin.

Closing remarks Although there are several areas of uncertainty with respect to the definition, usefulness and pathogenesis of MS, simple clinical tools exist which identify subjects at a higher risk of developing both type 2 diabetes and cardiovascular disease, and thus having high cardiometabolic risk. The management of these subjects is based principally on lifestyle measures, but various antihypertensive, lipid-lowering, insulin sensitizing, antiobesity and antiplatelet drugs could be helpful in reducing the cardiometabolic risk. This is particularly important in the hypertensive population. The presence of MS identifies individuals with high cardiometabolic risk who require an integrated therapeutic approach, considering an earlier use of

7mo. Congreso Virtual de Cardiología - 7th. Virtual Congress of Cardiology

specific antihypertensive drugs that do not increase the risk of type 2 diabetes, as well as other therapies counteracting the associated metabolic alterations present in every single patient. Population-based strategies are clearly necessary to reduce the impact of underlying risk factors for cardiometabolic risk (obesity, physical inactivity and atherogenic diet). However, there is general agreement that earlier and more aggressive therapy is required to further reduce the risk of new diabetes and cardiovascular disease, although evidence is scarce. Prospective, randomized trials addressing the effect of potentially beneficial treatments on cardiometabolic outcomes should be strongly encouraged.

BIBLIOGRAPHY 1. Eckel RH, Kahn R, Robertson RM, Rizza RA. Preventing cardiovascular disease and diabetes. Diabetes Care 2006; 29: 16971699. 2. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006; 444: 881-887. 3. 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). Final report. Circulation 2002; 106: 3143-3421. 4. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112: 27352752. 5. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome: a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 2006; 23: 469-480. 6. Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome. A joint statement of the International Diabetes Federation, the National Heart, Lung, and Blood Institute, the American Heart Association, the World Heart Federation, the International Atherosclerosis Society and the International Association for the Study of Obesity. Circulation 2009; 120: 1640-1645. 7. De la Sierra A, Romero R, Bonet J, Perez M, Lopez JS, Ravella R, et al. Prevalence and general features of the metabolic syndrome in the Spanish hypertensive population. Med Clin (Barc) 2006; 126: 406-409 [Article in Spanish]. 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). 2007 Guidelines for the Management of Arterial Hypertension. J Hypertens 2007; 25: 1105-1187. 9. Mancia G, Laurent S, Agabiti-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ, et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens 2009; 27: 2121-2158. 10.Galassi A, Reynolds K, He J. Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med 2006; 119: 812819. 11.Schillaci G, Pirro M, Vaudo G, Gemelli F, Marchesi S, Porcellati C, et al. Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol 2004; 43: 1817-1822. 12.Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 2005; 28: 1769-1778. 13.Kurella M, Lo JC, Chertow GM. Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults. J Am Soc Nephrol 2005; 16: 2134-2140. 14.Samuelsson O, Pennert K, Andersson O, Berglund G, Hedner T, Persson B, et al. Diabetes mellitus and raised serum triglyceride concentration in treated hypertension: are they of prognostic importance. Observational study. BMJ 1996; 314: 660-663. 15.Verdecchia P, Reboldi G, Angeli F, Borgioni C, Gattobigio R, Filippucci L, et al. Adverse prognostic significance of new diabetes in treated hypertensive subjects. Hypertension 2004; 43: 963-969. 16.Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet 2007; 369: 201207. 17.Kostis JB, Wilson AC, Freudenberger RS, Cosgrove NM, Pressel SL, Davis BR. 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. 18.Barzilay JI, Davis BR, Cutler JA, Pressel SL, Whelton PK, Basile J, 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: 2191-2201. 19.Alderman MH, Cohen H, Madhavan S. Diabetes and cardiovascular events in hypertensive patients. Hypertension 1999; 33: 11301134. 20.Klein S, Burke LE, Bray GA, Allison DB, Pi-Sunyer X, Hong Y, et al. Clinical implications of obesity with specific focus on cardiovascular disease: a statement for professionals from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2004; 110: 2952-2967. 21.Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403. 22.Cook NR, Cutler JA, Obarzanek E, Buring JE, Rexrode KM, Kumanyika SK, et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP). BMJ 2007; 334: 885 (Epub 2007 Apr 20). 23.Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray JA, Harsha D, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med 2001; 344: 310. 24.Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A, et al. Mediterranean diet, lifestyle factors, and 10year mortality in elderly European men and women: the HALE project. JAMA 2004; 292: 1433-1439. 25.De la Sierra A, Ruilope LM. Management of cardiovascular risk factors in patients with metabolic syndrome. Cardiovasc Hematol Agents Med Chem 2007; 5: 209-214. 26.Estacio RO, Jeffers BW, Hiatt WR, Biggerstaff SL, Gifford N, Schrier RW. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med 1998; 338: 645-652. 27.ADVANCE Collaborative Group. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007; 370: 829-840. 28.Lindholm LH, Ibsen H, Dahlöf B, Devereux RB, Beevers G, de Faire U, et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet

7mo. Congreso Virtual de Cardiología - 7th. Virtual Congress of Cardiology

2002; 359:1004-1010. 29.Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005; 366; 895-906. 30.Ostergren J, Poulter NR, Sever PS, Dahlöf B, Wedel H, Beevers G, et al. The Anglo-Scandinavian Cardiac Outcomes Trial: blood pressure-lowering limb: effects in patients with type II diabetes. J Hypertens 2008; 26: 2103-2111. 31.Jamerson K, Weber MA, Bakris GL, Dahlöf B, Pitt B, Shi V, et al. for the ACCOMPLISH trial investigators. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008; 359: 2417-2428. 32. The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547-1559. 33.Schupp M, Janke J, Clasen R, Unger T, Kintscher U. Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation 2004; 109: 2054-2057. 34.Bahadir O, Uzunlulu M, Oguz A, Bahadir MA. Effects of telmisartan and losartan on insulin resistance in hypertensive patients with metabolic syndrome. Hypertens Res 2007; 30: 49-53. 35.Derosa G, Fogari E, D’Angelo A, Cicero A, Salvadeo SA, Ragonesi PD, et al. Metabolic effects of telmisartan and irbesartan in type 2 diabetic patients with metabolic syndrome treated with rosiglitazone. J Clin Pharm Ther 2007; 32: 261-268. 36.Derosa G, Ragonesi PD, Mugellini A, Ciccarelli L, Fogari R. Effects of telmisartan compared with eprosartan on blood pressure control, glucose metabolism and lipid profile in hypertensive, type 2 diabetic patients: a randomized, double-blind, placebo-controlled 12-month study. Hypertens Res 2004; 27: 457-464. 37.Ruggenenti P, Fassi A, Ilieva AP, Bruno S, Iliev IP, Brusegan V, et al, Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med 2004;351:1941-51. 38.Parving HH, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Eng J Med 2001; 345: 870-878. 39.Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, et al. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med 2006; 354: 1685-1697. 40.Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361: 1149-1158. 41.Canner PL, Furberg CD, McGovern ME. Benefits of niacin in patients with versus without the metabolic syndrome and healed myocardial infarction (from the Coronary Drug Project). Am J Cardiol 2006; 97: 477-479. 42.Tenenbaum A, Motro M, Fisman EZ, Tanne D, Boyko V, Behar S. Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med 2005; 165: 1154-1160. 43.Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002; 359: 2072- 2077. 44.The DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006; 368: 1096-1105. 45.Hutton B, Fergusson D. Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials. Am J Clin Nutr 2004; 80: 1461-1468. 46.Antithrombotic Trialists' (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373: 1849-1860.

Curriculum of Dr. Alejandro De La Sierra - He is the Chairman of the Department of Medicine at the Hospital Mutua de Terrassa, Barcelona, Spain. - He also serves as Associate Professor at the University of Barcelona, Spain. - He’s main areas of interest are hypertension and cardiovascular prevention. - He has published more than 100 original papers in international peer-reviewed publications, as well as editorials, reviews and commentaries. - He has contributed to National and International Meetings on Hypertension and Cardiology with communications, lectures and chairmanship. - He received the Clinical Hypertension Specialist accreditation from the European Society of Hypertension (ESH) in 2001. - He is a member of several scientific societies, including the International Society of Hypertension (ISH), the ESH, fellow of the European Society of Cardiology and the American Heart Association, and past-president of the Catalan Society of Hypertension.

Publication: October 2011 Your questions, contributions and commentaries will be answered by the lecturer or experts on the subject in the High Blood Pressure list. Please fill in de form and Press the "Send" button. See message: September - October

7mo. Congreso Virtual de Cardiología - 7th. Virtual Congress of Cardiology

5 Question, contribution or commentary:

6 Name and Surname: Country: Argentina

6

E-Mail address: Re-type Email address: Send

Erase

© 1994- 2011 2011 CETIFAC - Bioengineering UNER - 7VCC ISBN 978-987-22746-2-7 Updated: 10/11/2011 - DHTML JavaScript Menu By Milonic.com - Webmaster - HonCode - pWMC