Trial Results, Guidelines, Journals, Risk Factors, and Drugs

Dahlof B, Sever PS, Poulter NR. Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Clinical Update II, ESC Congress 2005; September 3-7, 2005; Stockholm, Sweden.
Dahlof B, Sever PS, Poulter NR, for the ASCOT investigators. 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. Abstract
Sever PS, Dahlof B, Poulter NR, et al; ASCOT investigators. Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. J Hypertens. 2001;19:1139-1147. Abstract
Sever PS, Dahlof B, Poulter NR, Wedel H, et al; ASCOT investigators. 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. Abstract
Poulter NR, Wedel H, Dahlof B; the ASCOT investigators. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). Lancet. 2005;366:907-913. Abstract
Weber MA, Julius S, Kjeldsen SE, et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet. 2004;363:2049-2051. Abstract
Staessen JA, Birkenhager WH. Evidence that new antihypertensives are superior to older drugs. Lancet. 2005;366:869-871. Abstract
Sever PS, Dahlof B, Poulter NR, Wedel H. The Anglo-Scandinavian Cardiac Outcomes Trial: Morbidity-mortality outcomes in the blood pressure lowering arm of the trial (ASCOT-BPLA). Program and abstracts of the American College of Cardiology Annual Scientific Session 2005; March 6-9, 2005; Orlando, Florida. Late Breaking Clinical Trials 2.
NICE and British Hypertension Society in joint collaboration to review new data on treatment of hypertension. August 26, 2005. Available at: http://www.bhsoc.org/
Chobanian AV, Bakris GL, Black HR, et al; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206-1252. Abstract
World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21:1983-1992. Abstract
European Society of Hypertension/European Society of Cardiology Guidelines Committee. 2003 European Society of Hypertension/European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens. 2003;21:1011-1053. Abstract
Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal. Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005;28:2289-2304 and Diabetologia. 2005; epub ahead of print.
Reaven G. Role of insulin resistance in human disease. Diabetes. 1998;37:1595-1607.
World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO Consultation. Part 1: diagnosis and classification of diabetes mellitus. Geneva, Switzerland: World Health Organization; 1999. Available at: http://whqlibdoc.who.int/hq/1999/WHO_NCD_NCS_99.2.pdf
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: 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). JAMA. 2001;285:2486-2497. Abstract
Grundy SM, Brewer HB Jr, Cleeman JI, et al; National Heart, Lung and Blood Institute. American Heart Association. Definition of the metabolic syndrome: report of the National Heart, Lung and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004;109:433-438. Abstract
International Diabetes Federation. The IDF Consensus worldwide definition of the metabolic syndrome. Brussels, Belgium: International Diabetes Federation; 2004. Available at: http://www.idf.org/webdata/docs/Metabolic_syndrome_definition.pdf
Reaven GM. The metabolic syndrome; resquiat in pace. Clin Chem. 2005;51:931-938. Abstract
Reaven G. Just being alive is not good enough. Clin Chem. 2005;51:1354-1357. Abstract
Grundy SM. The metabolic syndrome still lives. Clin Chem. 2005;51:1352-1354. Abstract
Ford ES. Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults. Findings from the Third National Health and Nutrition Examination Survey. JAMA. 2002;287:356-359. Abstract
Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. 2005;45:/Circulation. 2005;112 (in press). Available at: www.acc.org and www.my.americanheart.org
Winslow R, Zimmerman R. High blood pressure: Doctors sever ties with medical journal. Wall Street Journal. July 29, 2005; B1.
Alderman MH, Barnes J, Blumenfeld JD, et al. The American Journal of Hypertension withdraws from its affiliation with the American Society of Hypertension. A report to our readers. Am J Hypertens. 2005;18:893.
The Journal of Clinical Hypertension selected as an official journal of the American Society of Hypertension, Inc. Press release. Le Jacq. August 25, 2005.
Liszka HA, Mainous AG, III, King DE, et al. Prehypertension and cardiovascular morbidity. Ann Fam Med. 2005;3:294-299. Abstract
Qureshi AI, Suri MFK, Kirmani JF, et al. Is prehypertension a risk factor for cardiovascular diseases? Stroke. 2005;36:1859-1863.
Giles TD. The New Definition of Hypertension. Program and abstracts of the 20th Annual Scientific Meeting of the American Society of Hypertension; May 14-18, 2005; San Francisco, California. Plenary Session I.
Giles TD, Berk BC, Black HR, et al. Expanding the definition and classification of hypertension. J Clin Hypertens. 2005;7:505-512.
Zureik M, Pilar Galan P, Bertrais S, et al. Parental longevity and 7-year changes in blood pressures in adult offspring. Hypertension. 2005;46:287-294. Abstract
Hercberg S, Galan P, Preziosi P, et al. The SUVIMAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004;164:2335-2342. Abstract
Grewen KM, Girdler SS, Amico J, et al. MD Effects of partner support on resting oxytocin, cortisol, norepinephrine, and blood pressure before and after warm partner contact. Psychosom Med. 2005;67:531-538. Abstract
Gillespie EL, White CM, Kardas M, et al. The impact of ACE inhibitors or angiotensin II type 1 receptor blockers on the development of new-onset type 2 diabetes. Diabetes Care. 2005;28:2261-2266. Abstract
Forman JP, Stampfer MJ, Curhan GC. Non-narcotic analgesic dose and risk of incident hypertension in US women. Hypertension. 2005;46:500-507. Abstract
Dedier J, Stampfer MJ, Hankinson SE, et al. Nonnarcotic analgesic use and the risk of hypertension in US women. Hypertension. 2004;164:1519-1524.
Curhan GC, Knight EL, Rosner B, et al. Frequency of analgesic use and risk of hypertension in younger women. Arch Intern Med. 2002;162:2204-2208. Abstract
Doctors question hypertension-painkillers link. ABC News. August 16, 2005. Available at: www.abcnews.go.com
Myogen reports positive results for darusentan phase 2b trial in resistant hypertension. August 18, 2005. Available at: http://www.myogen.com
Tonstad S, Tykarski A, Weissgarten J, et al; OBHT-001 Study Group. Efficacy and safety of topiramate in the treatment of obese subjects with essential hypertension. Am J Cardiol. 2005;96:243-251. Abstract
Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure. The sixth report of the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure (JNC VI). Arch Intern Med. 1997;157:2413-2446. Abstract

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US and European Diabetes Organizations Question Existence of Metabolic Syndrome

A joint statement issued by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) has called into question the existence of the metabolic syndrome, the cluster of risk factors, including hypertension, that is widely believed to predict the risk of developing cardiovascular disease. The ADA/EASD statement, published simultaneously in the September issue of Diabetes Care and in Diabetologia,^[13] argues that the metabolic syndrome is poorly defined, inconsistently used, and in need of further research to help understand whether and how it should be treated. There is "a lack of certainty regarding its pathogenesis," and "considerable doubt regarding its value as a cardiovascular disease risk marker," the statement says. Physicians, according to the authors, should not be diagnosing people with this "syndrome" or attempting to treat it as a separate malady until the science behind it is clear.

Since it was first described in 1998,^[14] the metabolic syndrome has been defined differently by a number of organizations, including the WHO,^[15] the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III),^[16,17] and, most recently, the International Diabetes Federation (IDF).^[18]

According to the WHO definition, for diagnosis of the syndrome a patient must present with glucose intolerance, impaired glucose tolerance, or diabetes and/or insulin resistance plus 2 or moreadditional risk factors: central obesity, high triglycerides or low HDL cholesterol; high blood pressure (≥ 140/90 mmHg); and microalbuminuria.

Diagnosis according to the ATP III criteria is by 3 or more of 5 risk factors: central obesity, high triglycerides, high blood pressure (≥ 130/85 mmHg), low HDL cholesterol, and high blood glucose.

The IDF definition is based on central obesity plus 2 of 4 factors: high triglycerides, low HDL cholesterol, high blood pressure (≥ 130/85 mmHg or antihypertensive treatment), and high fasting blood glucose or diabetes.

The ADA/EASD statement says that the fact that these definitions conflict implies that there is no clear evidence base for what should or should not be included. It says that the criteria for the syndrome are ambiguous and incomplete and that the rationale for thresholds are ill-defined; the value of including diabetes in the definition is questionable; insulin resistance as the unifying etiology is uncertain, and there is no clear basis for including/excluding other cardiovascular disease risk factors.

The cardiovascular risk associated with the "syndrome" appears no greater than the sum of its parts, according to the statement. Treatment of the "syndrome" is no different from treatments for each of its components and in patients with diabetes or known vascular disease, and inordinate attention to the "syndrome" can impede appropriate care, the authors believe. People should not be diagnosed with the "metabolic syndrome," as doing so will mislead the patient into believing that he or she has a unique disease, instead of well-known cardiovascular risk factors, the authors state.

The authors of the statement believe that "the metabolic syndrome requires much more study before its designation as a 'syndrome' is truly warranted and before its clinical utility is adequately defined." They recommend that doctors continue to evaluate patients for the presence of other cardiovascular risk factors when one is discovered; aggressively treat individual cardiovascular risk factors; avoid labeling patients with the term "metabolic syndrome;" and not attempt to prescribe a treatment for this "syndrome" until new, solid evidence is obtained.

The metabolic syndrome has also recently been declared "dead" by the man who originated the concept (as "Syndrome X"), Gerald Reaven, MD (Stanford University School of Medicine; Stanford, California).^[19,20] Dr. Reaven has declared himself "unimpressed" by both the WHO and ATP III forms of the metabolic syndrome. He believes that physicians should focus on individual cardiovascular disease risk factors instead of whether or not individuals are obese or whether they meet a certain number of criteria for making a diagnosis of the metabolic syndrome. However, Scott M. Grundy, MD (University of Southwest Medical Center; Dallas, Texas), who was a member of the team that issued the ATP III criteria as well as a consultant to the group that developed the IDF definition, replied that he see still sees "signs of life" in the concept, which "represents a powerful hypothesis that unifies the metabolic factors underlying the development of both atherosclerotic cardiovascular disease and diabetes" and "a useful clinical tool."^[21]

A recent analysis applying ATP III criteria estimated that approximately 24% of adults in the United States have the metabolic syndrome.^[22]