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      The PPARGC1A Gly482Ser polymorphism is associated with left ventricular diastolic dysfunction in men

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          Abstract

          Background

          The Gly482Ser polymorphism in peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A) has been demonstrated to be associated with diabetes, obesity and hypertension, all of which are important risk factors for left ventricular diastolic dysfunction.

          Methods

          The PPARGC1A Gly482Ser polymorphism was genotyped in a community-based cohort of 499 men and 533 women, who also underwent an echocardiographic examination to determine their left ventricular diastolic function. The association between the polymorphism and the presence of diastolic dysfunction was evaluated using logistic regression models.

          Results

          The Ser allele of the PPARGC1A Gly482Ser polymorphism was significantly associated with a lower risk of diastolic dysfunction in men, but not in women. In a model adjusting for potential confounders (age, body mass index, leisure time physical activity, hypertension and diabetes) the results were still significant and substantial (odds ratio 0.13, 95% confidence interval 0.03–0.54, p for trend = 0.004). The results were consistent in a series of models, and they imply a multiplicative, protective effect of the Ser allele, with lower risk of diastolic dysfunction for each copy of the allele.

          Conclusion

          The Ser allele of the PPARGC1A Gly482Ser polymorphism was associated with decreased risk of diastolic left ventricular dysfunction in men, but not in women, in our large community-based sample. It was associated with a substantially decreased risk, even after adjustment for potential confounders. The clinical importance of the findings has to be established in further studies.

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          Most cited references 51

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          The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

          "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.
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            Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.

            The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered to > or =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasma > or =6.1 to or =5.6 to <6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.
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              Obesity and the risk of heart failure.

              Extreme obesity is recognized to be a risk factor for heart failure. It is unclear whether overweight and lesser degrees of obesity also pose a risk. We investigated the relation between the body-mass index (the weight in kilograms divided by the square of the height in meters) and the incidence of heart failure among 5881 participants in the Framingham Heart Study (mean age, 55 years; 54 percent women). With the use of Cox proportional-hazards models, the body-mass index was evaluated both as a continuous variable and as a categorical variable (normal, 18.5 to 24.9; overweight, 25.0 to 29.9; and obese, 30.0 or more). During follow-up (mean, 14 years), heart failure developed in 496 subjects (258 women and 238 men). After adjustment for established risk factors, there was an increase in the risk of heart failure of 5 percent for men and 7 percent for women for each increment of 1 in body-mass index. As compared with subjects with a normal body-mass index, obese subjects had a doubling of the risk of heart failure. For women, the hazard ratio was 2.12 (95 percent confidence interval, 1.51 to 2.97); for men, the hazard ratio was 1.90 (95 percent confidence interval, 1.30 to 2.79). A graded increase in the risk of heart failure was observed across categories of body-mass index. The hazard ratios per increase in category were 1.46 in women (95 percent confidence interval, 1.23 to 1.72) and 1.37 in men (95 percent confidence interval, 1.13 to 1.67). In our large, community-based sample, increased body-mass index was associated with an increased risk of heart failure. Given the high prevalence of obesity in the United States, strategies to promote optimal body weight may reduce the population burden of heart failure. Copyright 2002 Massachusetts Medical Society
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                Author and article information

                Affiliations
                [1]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
                [2]Department of Clinical Sciences, Community Medicine, Lund University, Malmö University Hospital, Malmö, Sweden
                [3]Department of Clinical Sciences, Clinical Obesity, Lund University, Malmö University Hospital, Malmö, Sweden
                [4]Department of Cardiology, Skaraborg Hospital, Skövde, Sweden
                [5]Skaraborg Institute, Skövde, Sweden
                [6]Department of Public Health and Community Medicine/Primary Health Care, The Sahlgrenska Academy at Gothenburg University, Sweden
                Contributors
                Journal
                BMC Cardiovasc Disord
                BMC Cardiovascular Disorders
                BioMed Central
                1471-2261
                2008
                11 December 2008
                : 8
                : 37
                2637232
                1471-2261-8-37
                19077249
                10.1186/1471-2261-8-37
                Copyright © 2008 Ingelsson et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Research Article

                Cardiovascular Medicine

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