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Bays H, Zhu D, Schumacher H. Single-Pill Combination of Telmisartan and Hydrochlorothiazide: Studies and Pooled Analyses of Earlier Hypertension Treatment. High Blood Press Cardiovasc Prev. 2014 Feb 4. [Epub ahead of print] PubMed PMID: 24493330

Bays H, Gao P, Völker B, Mattheus M, Ruilope LM, Zhu D. Efficacy of Single-Pill Combination of Telmisartan 80 mg and Hydrochlorothiazide 25 mg in Patients with Cardiovascular Disease Risk Factors: A Prospective Subgroup Analysis of a Randomized, Double-Blind, and Controlled Trial. Int J Hypertens. 2013;2013:749830. doi: 10.1155/2013/749830. Epub 2013 Apr 4. PubMed PMID: 23653855; PubMed Central PMCID: PMC3638649.

Zhu DL, Bays H, Gao P, Mattheus M, Voelker B, Ruilope LM. Efficacy and tolerability of a single-pill combination of telmisartan 80 mg and hydrochlorothiazide 25 mg according to age, gender, race, hypertension severity, and previous antihypertensive use: planned analyses of a randomized trial. Integr Blood Press Control. 2013 3;6:1-14..

Zhu DL, Bays H, Gao P, Mattheus M, Voelker B, Ruilope LM. Efficacy and Tolerability of Initial Therapy With Single-Pill Combination Telmisartan/Hydrochlorothiazide 80/25 mg in Patients With Grade 2 or 3 Hypertension: A Multinational, Randomized, Double-Blind, Active-Controlled Trial. Clin Ther. 2012;34(7):1613-24.

Bays HE. Adiposopathy: Is "Sick Fat" a Cardiovascular Disease? Journal of the American College of Cardiology. 2011;57:2461-2473. (CLICK HERE FOR ONLINE MEDSCAPE REPRINT OF THIS ARTICLE)

Bays HE, Gonzalez-Campoy JM, Schorr AB. What men should know about metabolic syndrome, adiposopathy, and "sick fat." Int J Clin Pract. 2010;64:1735-1739.

Bays HE, Roth EM, McKenney JM, Kelly MT, Thakker KM, Setze CM, Obermeyer K, Sleep DJ. The effects of fenofibric acid alone and with statins on the prevalence of metabolic syndrome and its diagnostic components in patients with mixed dyslipidemia. Diabetes Care. 2010 Sep;33(9):2113-6

Bays H. Phentermine, topiramate, and their combination for the treatment of adiposopathy ("sick fat") and metabolic disease. Expert Rev. Cardiovasc. Ther. 2010; 8(12):1777-801.

Abstract: Positive caloric balance often causes pathologic adipocyte and adipose tissue anatomical and functional changes (termed adiposopathy or 'sick fat'), which may lead to pathogenic adipocyte and adipose tissue responses and metabolic disease. Fat weight loss may improve adiposopathy, and thus improve metabolic disease in overweight patients. Unfortunately, the efficacy of nonsurgical weight loss therapies is often limited due to redundant physiological systems that help 'protect' against starvation and/or negative caloric balance. One strategy to overcome these limitations is to combine weight loss drug therapies having complementary mechanisms of action, thereby affecting more than one physiologic process influencing body fat accumulation. Phentermine is a noradrenergic sympathomimetic amine approved for short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide derivative of the naturally occurring sugar monosaccharide d-fructose approved as treatment for migraine headaches and seizure disorders. Although known to facilitate weight loss since its approval, topiramate monotherapy does not have a regulatory indication as an anti-obesity agent. Phentermine HCl / topiramate controlled-release (PHEN/TPM CR) is a combination agent containing immediaterelease phentermine and controlled-release topiramate. Clinical trials involving thousands of patients demonstrate PHEN/TPM CR to be effective in improving the weight of patients, and also effective in improving adiposopathy-associated metabolic diseases. This review examines the pathophysiology of adiposopathy as a contributor to metabolic disease, the data supporting phentermine monotherapy, topiramate monotherapy and their combination as anti-obesity and anti-adiposopathy agents, and the preliminary evidence supporting PHEN/TPM CR as a generally well-tolerated and effective agent to improve metabolic disease.[CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE, Maccubbin D, Meehan AG, Kuznetsova O, Mitchel YB, Paolini JF. Blood pressure-lowering effects of extended-release nacin/laropiprant combinaiton: A post hoc analysis of a 24-week, placebo-controlled trial in dyslipidemic patients. Clin ther. 2009;1:115-22.

Bays HE. Lorcaserin and adiposopathy: 5-HT2c agonism as a treatment for ‘sick fat’ and metabolic disease. Expert Rev. Cardiovasc. Ther. 7(11), 1429–1445 (2009)

Abstract: Agonists of 5-hydroxytryptamine (5-HT; serotonin) receptors promote loss of excessive body fat (adiposity) and improve metabolic parameters associated with adiposity-induced adipose tissue dysfunction (adiposopathy or ‘sick fat’). By improving adipose tissue pathogenic endocrine and immune responses in overweight patients, 5-HT receptor agonists may improve metabolic disease. Lorcaserin (APD-356) is a selective 5-HT2c receptor agonist that promotes weight loss. Probably owing to its selectivity for the 5-HT2c receptor, clinical trial evidence supports that lorcaserin does not adversely affect heart valves or pulmonary artery pressure. This review examines: the mechanisms by which serotonergic pathways improve adiposity and adiposopathy; historical data and perspective regarding the efficacy and safety of prior 5-HT agonists; speculation regarding future paradigms in treating adiposopathy; and why lorcaserin may prove to be a safe and generally well-tolerated agent that not only improves the weight of patients, but also improves the health of patients. [CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE, Laferrere B, Dixon J, Arrone L, Gonzalez-Campoy JM, Apovian C, Wolfe BM. "Adiposopathy and bariatric surgery: is 'sick fat' a surgical disease?" Consensus. Int J Clin Pract Sept. 2009 63(9) 1285-1300

Objective: To review how bariatric surgery in obese patients may effectively treatadiposopathy (pathogenic adipose tissue or ‘sick fat’), and to provide clinicians arationale as to why bariatric surgery is a potential treatment option for overweightpatients with type 2 diabetes, hypertension, and dyslipidaemia. Methods: A groupof clinicians, researchers, and surgeons, all with a background in treating obesityand the adverse metabolic consequences of excessive body fat, reviewed the medicalliterature regarding the improvement in metabolic disease with bariatric surgery. Results: Bariatric surgery improves metabolic disease through multiple, likelyinterrelated mechanisms including: (i) initial acute fasting and diminished caloricintake inherent with many gastrointestinal surgical procedures; (ii) favourable alterationsin gastrointestinal endocrine and immune responses, especially with bariatricsurgeries that reroute nutrient gastrointestinal delivery such as gastric bypass procedures;and (iii) a decrease in adipose tissue mass. Regarding adipose tissuemass, during positive caloric balance, impaired adipogenesis (resulting in limitationsin adipocyte number or size) and visceral adiposity are anatomic manifestationsof pathogenic adipose tissue (adiposopathy). This may cause adverse adiposetissue endocrine and immune responses that lead to metabolic disease. A decreasein adipocyte size and decrease in visceral adiposity, as often occurs with bariatricsurgery, may effectively improve adiposopathy, and thus effectively treat metabolicdisease. It is the relationship between bariatric surgery and its effects upon pathogenicadipose tissue that is the focus of this discussion. Conclusions: In selectiveobese patients with metabolic disease who are refractory to medical management,adiposopathy is a surgical disease. [CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE, Gonzalez-Campoy JM, Henry RR, Bergman DA, Schorr AB, Rodbard. Is adiposopathy ("sick fat") an endocrine disease? Int J Clin Pract. 2008:10:1474-83.

Abstract: OBJECTIVE: To review current consensus and controversy regarding whether obesity is a 'disease', examine the pathogenic potential of adipose tissue to promote metabolic disease and explore the merits of 'adiposopathy' and 'sick fat' as scientifically and clinically useful terms in defining when excessive body fat may represent a 'disease'. METHODS: A group of clinicians and researchers, all with a background in endocrinology, assembled to evaluate the medical literature, as it pertains to the pathologic and pathogenic potential of adipose tissue, with an emphasis on metabolic diseases that are often promoted by excessive body weight. RESULTS: The data support pathogenic adipose tissue as a disease. Challenges exist to convince many clinicians, patients, healthcare entities and the public that excessive body fat is often no less a 'disease' than the pathophysiological consequences related to anatomical abnormalities of other body tissues. 'Adiposopathy' has the potential to scientifically define adipose tissue anatomic and physiologic abnormalities, and their adverse consequences to patient health. Adiposopathy acknowledges that when positive caloric balance leads to adipocyte hypertrophy and visceral adiposity, then this may lead to pathogenic adipose tissue metabolic and immune responses that promote metabolic disease. From a patient perspective, explaining how excessive caloric intake might cause fat to become 'sick' also helps provide a rationale for patients to avoid weight gain. Adiposopathy also better justifies recommendations of weight loss as an effective therapeutic modality to improve metabolic disease in overweight and obese patients. CONCLUSION: Adiposopathy (sick fat) is an endocrine disease.[CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE, Laferrere B, Dixon J, Arrone L, Gonzalez-Campoy JM, Apovian C, Wolfe BM. "Adiposopathy and bariatric surgery: is 'sick fat' a surgical disease?" Consensus. Int J Clin Pract Sept. 2009 63,9, 1285-1300

Objective: To review how bariatric surgery in obese patients may effectively treatadiposopathy (pathogenic adipose tissue or ‘sick fat’), and to provide clinicians arationale as to why bariatric surgery is a potential treatment option for overweightpatients with type 2 diabetes, hypertension, and dyslipidaemia. Methods: A groupof clinicians, researchers, and surgeons, all with a background in treating obesityand the adverse metabolic consequences of excessive body fat, reviewed the medicalliterature regarding the improvement in metabolic disease with bariatric surgery. Results: Bariatric surgery improves metabolic disease through multiple, likelyinterrelated mechanisms including: (i) initial acute fasting and diminished caloricintake inherent with many gastrointestinal surgical procedures; (ii) favourable alterationsin gastrointestinal endocrine and immune responses, especially with bariatricsurgeries that reroute nutrient gastrointestinal delivery such as gastric bypass procedures;and (iii) a decrease in adipose tissue mass. Regarding adipose tissuemass, during positive caloric balance, impaired adipogenesis (resulting in limitationsin adipocyte number or size) and visceral adiposity are anatomic manifestationsof pathogenic adipose tissue (adiposopathy). This may cause adverse adiposetissue endocrine and immune responses that lead to metabolic disease. A decreasein adipocyte size and decrease in visceral adiposity, as often occurs with bariatricsurgery, may effectively improve adiposopathy, and thus effectively treat metabolicdisease. It is the relationship between bariatric surgery and its effects upon pathogenicadipose tissue that is the focus of this discussion. Conclusions: In selectiveobese patients with metabolic disease who are refractory to medical management,adiposopathy is a surgical disease. [CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE. "Sick Fat," metabolic disease, and atherosclerosis. Am J Med. 2009;122(1Suppl):S26-37.

Abstract: Atherosclerotic coronary heart disease (CHD) is the most common cause of morbidity and mortality among men and women in developed nations. The obesity epidemic contributes to the increasing prevalence of high blood sugar (as may be found in patients with diabetes mellitus and metabolic syndrome), high blood pressure, and dyslipidemia--all CHD risk factors. Metabolic syndrome describes the common clinical finding wherein component CHD risk factors cluster within a single patient, but this term does not identify any unified pathophysiologic process. However, a component of the metabolic syndrome is abdominal obesity, which does reflect an anatomic manifestation of a "common-soil" pathophysiologic process that promotes the onset of CHD risk factors, and thus increases CHD risk. Adiposopathy ("sick fat") is anatomically characterized by visceral adiposity and adipocyte hypertrophy; it is manifested physiologically by a net increase in release of free fatty acids and by pathogenic adipose tissue metabolic/immune responses that promote metabolic disease and increase CHD risk. Understanding the relation of adiposopathy to CHD risk factors and recognizing the importance of treating both the "cause and effect" of metabolic diseases are critical toward a comprehensive approach in reducing CHD risk. Regarding the "cause," clinicians and their patients should be diligent regarding appropriate nutritional and lifestyle interventions that may favorably affect health. Regarding the "effect," clinicians and their patients should be equally diligent toward appropriate pharmaceutical interventions that reduce CHD risk factors when nutritional and lifestyle interventions do not sufficiently achieve desired metabolic treatment goals.[CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE, Rader DJ. Does nicotinic acid (niacin) lower blood pressure? Int J Clin Pract January 2009;63:151–159.

Bays HE, Gonzalez-Campoy JM, Henry RR, Bergman DA, Schorr AB, Rodbard. Is adiposopathy ("sick fat") an endocrine disease? Int J Clin Pract. 2008:10:1474-83.

Bays HE, Gonzalez-Campoy JM, Bray GA, Kitabchi AE, Bergman DA, Schorr AB, Rodbard HW, Henry RR.  Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity.  Expert Rev Cardiovasc Ther. 2008;3:343-368.

Abstract:  When caloric intake exceeds caloric expenditure, the positive caloric balance and storage of energy in adipose tissue often causes adipocyte hypertrophy and visceral adipose tissue accumulation. These pathogenic anatomic abnormalities may incite metabolic and immune responses that promote Type 2 diabetes mellitus, hypertension and dyslipidemia. These are the most common metabolic diseases managed by clinicians and are all major cardiovascular disease risk factors. 'Disease' is traditionally characterized as anatomic and physiologic abnormalities of an organ or organ system that contributes to adverse health consequences.  Using this definition, pathogenic adipose tissue is no less a disease than diseases of other body organs. This review describes the consequences of pathogenic fat cell hypertrophy and visceral adiposity, emphasizing the mechanistic contributions of genetic and environmental predispositions, adipogenesis, fat storage, free fatty acid metabolism, adipocyte factors and inflammation. Appreciating the full pathogenic potential of adipose tissue requires an integrated perspective, recognizing the importance of 'cross-talk' and interactions between adipose tissue and other body systems. Thus, the adverse metabolic consequences that accompany fat cell hypertrophy and visceral adiposity are best viewed as a pathologic partnership between the pathogenic potential adipose tissue and the inherited or acquired limitations and/or impairments of other body organs. A better understanding of the physiological and pathological interplay of pathogenic adipose tissue with other organs and organ systems may assist in developing better strategies in treating metabolic disease and reducing cardiovascular disease risk.  [CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE, Chapman RH, Grandy S.  The relationship of body mass index to diabetes mellitus, hypertension and dyslipidaemia: comparison of data from two national surveys.  Int J Clin Pract, May 2007, 61, 5, 737–747

Bays H, Blonde L, Rosenson R.  Adiposopathy:  how do diet, exercise, and weight loss drug therapies improve metabolic disease in overweight patients.  Expert Rev. Cardiovasc. Ther. 4(6), 871–895 (2006)  [Click here for a free download of this article]

Abstract:  An increase in bodyweight is generally associated with an increased risk of excessive fat-related metabolic diseases (EFRMD), including Type 2 diabetes mellitus, hypertension and dyslipidemia. However, not all patients who are overweight have EFRMD, and not all patients with EFRMD are significantly overweight. The adipocentric paradigm provides the basis for a unifying, pathophysiological process whereby fat gain in susceptible patients leads to fat dysfunction (‘sick fat’), and wherein pathological abnormalities in fat function (adiposopathy) are more directly related to the onset of EFRMD than increases in fat mass (adiposity) alone. But just as worsening fat function worsens EFRMD, improved fat function improves EFRMD. Peroxisome proliferator-activated receptor-γ agonists increase the recruitment, proliferation and differentiation of preadipocytes (‘healthy fat’) and cause apoptosis of hypertrophic and dysfunctional (including visceral) adipocytes resulting in improved fat function and improved metabolic parameters associated with EFRMD. Weight loss interventions, such as a hypocaloric diet and physical exercise, in addition to agents such as orlistat, sibutramine and cannabinoid receptor antagonists, may have favorable effects upon fat storage (lipogenesis and fat distribution), nutrient metabolism (such as free fatty acids), favorable effects upon adipose tissue factors involved in metabolic processes and inflammation, and enhanced ‘cross-talk’ with other major organ systems. In some cases, weight loss therapeutic agents may even affect metabolic parameters and adipocyte function independently of weight loss alone, suggesting that the benefit of these agents in improving EFRMD may go beyond their efficacy in weight reduction. This review describes how adiposopathy interventions may affect fat function, and thus improve EFRMD.

Bays H, Ballantyne C.  Adiposopathy:  why do adiposity and obesity cause metabolic disease?  Future Lipidol. 2006 1(4), 389-420

Abstract: In the adipocentric paradigm, fat health affects patient health. Adiposopathy (‘pathos’ of adipose tissue or fat dysfunction) is more directly associated with excessive fat-related metabolic disease (EFRMD) than adiposity (increased fat mass) alone. Examples of adipocyte factors whose dysmetabolism may contribute to Type 2 diabetes mellitus include: 11 β-hydroxysteroid dehydrogenase type 1, acylation-stimulating protein, adiponectin, adipsin, angiotensinogen, autotaxin, ceramide, free fatty acids, hormone-sensitive lipase, interleukin-6, insulin-like growth factor-1, leptin, lipin, lysophospholipids, perilipin, phosphoenolpyrovate carboxykinase, plasminogen activator inhibitor-1, resistin, retinol-binding protein, tumor necrosis factor-α, visceral adipose tissue-derived serpin and visfatin. Excessive body fat may lead to hypertension due to physical compression of kidneys, sleep apnea, and other mechanisms. Examples of adipocyte factors whose dysmetabolism may contribute to hypertension include: 11 β-hydroxysteroid dehydrogenase type 1, adiponectin, angiotensinogen, angiotensin I and II, angiotensin-converting enzyme, renin, cathepsin, chymase, free fatty acids, interleukin-6 and leptin. Examples of adipocyte factors whose dysmetabolism may contribute to dyslipidemia include: 11 β-hydroxysteroid dehydrogenase type 1, acylation-stimulating protein, adipophilin, adiponectin, adipsin, cholesteryl ester-transfer protein, free fatty acids, hormone-sensitive lipase, leptin, lipoprotein lipase, perilipin, phospholipid transfer protein, sex hormones and tumor necrosis factor-α. Numerous other adipocyte factors may directly affect atherosclerosis and cardiomyopathy. A better understanding and recognition of how fat weight gain contributes to EFRMD will substantially affect the research and development of therapeutic interventions that may treat or prevent adiposopathy, and dramatically influence which patients with EFRMD are best treated and how.

Bays HE.  Dujovne CA.  Adiposopathy is a More Rational Treatment Target for Metabolic Disease Than Obesity Alone.  Current Atherosclerosis Reports 2006, 8:144–156

Bays H.  Adiposopathy:  role of adipocyte factors in a new paradigm.  Expert Rev Cardiovasc Ther. 2005;3:187-9

Bays HE.  Adiposopathy, metabolic syndrome, quantum physics, general relativity, chaos and the Theory of Everything.  Expert Rev. Cardiovasc. Ther. 3(3), 393–404 (2005)

Abstract:  Excessive fat (adiposity) and dysfunctional fat (adiposopathy) constitute the most common worldwide epidemics of our time – and perhaps of all time. Ongoing efforts to explain how the micro (adipocyte) and macro (body organ) biologic systems interact through function and dysfunction in promoting Type 2 diabetes mellitus, hypertension and dyslipidemia are not unlike the mechanistic and philosophical thinking processes involved in reconciling the micro (quantum physics) and macro (general relativity) theories in physics. Currently, the term metabolic syndrome refers to a constellation of consequences often associated with excess body fat and is an attempt to unify the associations known to exist between the four fundamental metabolic diseases of obesity, hyperglycemia (including Type 2 diabetes mellitus), hypertension and dyslipidemia. However, the association of adiposity with these metabolic disorders is not absolute and the metabolic syndrome does not describe underlying causality, nor does the metabolic syndrome necessarily reflect any reasonably related pathophysiologic process. Just as with quantum physics, general relativity and the four fundamental forces of the universe, the lack of an adequate unifying theory of micro causality and macro consequence is unsatisfying, and in medicine, impairs the development of agents that may globally improve both obesity and obesity-related metabolic disease. Emerging scientific and clinical evidence strongly supports the novel concept that it is not adiposity alone, but rather it is adiposopathy that is the underlying cause of most cases of Type 2 diabetes mellitus, hypertension and dyslipidemia. Adiposopathy is a plausible Theory of Everything for mankind’s greatest metabolic epidemics.

Bays H, Abate N, Chandalia M.  Adiposopathy:  Sick Fat Causes High Blood Sugar, High Blood Pressure, and Dyslipidemia.  Future Cardiology (2005) 1(1), 39-59.

Abstract:  Adiposopathy is defined as pathological adipose tissue function that may be promoted and exacerbated by fat accumulation (adiposity) and sedentary lifestyle in genetically susceptible patients. Adiposopathy is a root cause of some of the most common metabolic diseases observed in clinical practice, including Type 2 diabetes mellitus, hypertension and dyslipidemia. The most common term for the metabolic consequences of adiposopathy is currently ‘the metabolic syndrome’. Drug usage to treat the metabolic syndrome has focused on the safety and efficacy of treatments directed towards individual components of the metabolic syndrome, and not so much upon adiposopathy itself. However, enough is known about the pathophysiology of adiposopathy to propose diagnostic criteria. Regulatory issues are important obstacles to the research and development of new drug treatments for the metabolic syndrome. It is hoped that these obstacles can, to some extent, be addressed and overcome by clearly defining and increasing our understanding of adiposopathy.  (NOTE:  This above article is copyrighted.  All reprints should be obtained through Ashley Publication Ltd.)

Bays HE, Dujovne CA. Management of Multiple Cardiovascular Risk Factors in Primary Care. Resident and Staff Physician 1994;40:1-28

 

ABSTRACTS

Bays HE, Schmitz K, Christian A, Ritchey M, Anderson J. Raisins and Blood Pressure: A Randomized, Controlled Trial. Poster abstract presentation. 61st Annual Scientific Session of the American College of Cardiology. March 25 2012. Chicago Illinois USA

Dingliang Zhu, Harold Bays, Pingjin Gao, Vivian GuW, Michaela Mattheus, Luis Miguel Ruilope. Efficacy and safety of single-pill combination of telmisartan 80 mg plus hydrochlorothiazide 25 mg as first line therapy for patients with grade 2 or grade 3 hypertension. 23rd Scientific Meeting of the International Society of Hypertension, Vancouver, Canada, September 26-30, 2010

HE Bays, JS Park, K Reilly, J Triscari and AST investigators Irbesartan safety and effectiveness: a post-marketing surveillance study.  American Journal of Hypertension.  Vol 12, Issue 4, Supplement 1, April 1990, page 120

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