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Bradley A. Maron

Bio: Bradley A. Maron is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Pulmonary hypertension & Medicine. The author has an hindex of 34, co-authored 163 publications receiving 4217 citations. Previous affiliations of Bradley A. Maron include Veterans Health Administration & Harvard University.


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TL;DR: The misclassification of benign variants as pathogenic variants that were found in this study shows the need for sequencing the genomes of diverse populations, both in asymptomatic controls and the tested patient population.
Abstract: BackgroundFor more than a decade, risk stratification for hypertrophic cardiomyopathy has been enhanced by targeted genetic testing. Using sequencing results, clinicians routinely assess the risk of hypertrophic cardiomyopathy in a patient’s relatives and diagnose the condition in patients who have ambiguous clinical presentations. However, the benefits of genetic testing come with the risk that variants may be misclassified. MethodsUsing publicly accessible exome data, we identified variants that have previously been considered causal in hypertrophic cardiomyopathy and that are overrepresented in the general population. We studied these variants in diverse populations and reevaluated their initial ascertainments in the medical literature. We reviewed patient records at a leading genetic-testing laboratory for occurrences of these variants during the near-decade-long history of the laboratory. ResultsMultiple patients, all of whom were of African or unspecified ancestry, received positive reports, with va...

555 citations

Journal ArticleDOI
TL;DR: It is shown that aldosterone decreased endothelial G6PD expression and activity in vitro, resulting in increased oxidant stress and decreased NO• levels—similar to what is observed in G6 PD-deficient endothelial cells.
Abstract: Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanisms by which aldosterone promotes endothelial dysfunction remain unknown Glucose-6-phosphate dehydrogenase (G6PD) modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO(*)) Here we show that aldosterone (10(-9)-;10(-7) mol/l) decreased endothelial G6PD expression and activity in vitro, resulting in increased oxidant stress and decreased NO(*) levels-similar to what is observed in G6PD-deficient endothelial cells Aldosterone decreased G6PD expression by increasing expression of the cyclic AMP-response element modulator (CREM) to inhibit cyclic AMP-response element binding protein (CREB)-mediated G6PD transcription In vivo, infusion of aldosterone decreased vascular G6PD expression and impaired vascular reactivity These effects were abrogated by spironolactone or vascular gene transfer of G6pd These findings demonstrate that aldosterone induces a G6PD-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6PD activity

320 citations

Journal ArticleDOI
TL;DR: The unique biochemical profile of homocysteine is characterized by chemical reactivity supporting a wide range of molecular effects and by a tendency to promote oxidant stress-induced cellular toxicity, including the primary prevention of atherothrombotic disease in individuals at low or intermediate risk, or those with severe hyperhomocysteinemia.
Abstract: The unique biochemical profile of homocysteine is characterized by chemical reactivity supporting a wide range of molecular effects and by a tendency to promote oxidant stress-induced cellular toxicity. Numerous epidemiological reports have established hyperhomocysteinemia as an independent risk factor for cardiovascular disease, cerebrovascular disease, dementia-type disorders, and osteoporosis-associated fractures. Although combined folic acid and B-vitamin therapy substantially reduces homocysteine levels, results from randomized placebo-controlled clinical trials testing the effect of vitamin therapy on outcome in these diseases have generally fallen short of expectations. These results have led some to abandon homocysteine monitoring in the management of patients with cardiovascular or cognitive disorders. These trials, however, have generally included patients with only mildly elevated homocysteine levels and have not addressed several clinical scenarios in which homocysteine reduction may be effective, including the primary prevention of atherothrombotic disease in individuals at low or intermediate risk, or those with severe hyperhomocysteinemia.

259 citations

Journal ArticleDOI
TL;DR: In this paper, the Cox proportional hazards models were used to evaluate the association between pulmonary artery pressure (mPAP) and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates.
Abstract: Background—Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based primarily on expert consensus opinion, PH is defined by a mean pulmonary artery pressure (mPAP) ≥25 mm Hg. Although mPAP levels below this threshold are common among populations at risk for PH, the relevance of mPAP <25 mm Hg to clinical outcome is unknown. Methods and Results—We analyzed retrospectively all US veterans undergoing right heart catheterization (2007–2012) in the Veterans Affairs healthcare system (n=21 727; 908-day median follow-up). Cox proportional hazards models were used to evaluate the association between mPAP and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates. When treating mPAP as a continuous variable, the mortality hazard increased beginning at 19 mm Hg (hazard ratio [HR]=1.183; 95% confidence interval [CI], 1.004–1.393) relative to 10 mm Hg. Therefore, patients were stratified into 3 groups: (1) referent (≤18 mm Hg;...

259 citations

Journal ArticleDOI
TL;DR: In this article, microRNA-21 (miR-21) is predicted as a PH-modifying microRNA, regulating targets integral to bone morphogenetic protein (BMP) and Rho/Rho-kinase signaling as well as functional pathways associated with hypoxia, inflammation, and genetic haploinsufficiency of BMP receptor type 2.
Abstract: Background—Pulmonary hypertension (PH) is driven by diverse pathogenic etiologies. Owing to their pleiotropic actions, microRNA molecules are potential candidates for coordinated regulation of these disease stimuli. Methods and Results—Using a network biology approach, we identify microRNA associated with multiple pathogenic pathways central to PH. Specifically, microRNA-21 (miR-21) is predicted as a PH-modifying microRNA, regulating targets integral to bone morphogenetic protein (BMP) and Rho/Rho-kinase signaling as well as functional pathways associated with hypoxia, inflammation, and genetic haploinsufficiency of BMP receptor type 2. To validate these predictions, we have found that hypoxia and BMP receptor type 2 signaling independently upregulate miR-21 in cultured pulmonary arterial endothelial cells. In a reciprocal feedback loop, miR-21 downregulates BMP receptor type 2 expression. Furthermore, miR-21 directly represses RhoB expression and Rho-kinase activity, inducing molecular changes consistent...

254 citations


Cited by
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TL;DR: The Statistical Update brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update each year.
Abstract: Appendix I: List of Statistical Fact Sheets. URL: http://www.americanheart.org/presenter.jhtml?identifier=2007 We wish to thank Drs Brian Eigel and Michael Wolz for their valuable comments and contributions. We would like to acknowledge Tim Anderson and Tom Schneider for their editorial contributions and Karen Modesitt for her administrative assistance. Disclosures View this table: View this table: View this table: # Summary {#article-title-2} Each year, the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on disease …

6,176 citations

Journal ArticleDOI
TL;DR: This chapter describes the most important sources and the types of data the AHA uses from them and other government agencies to derive the annual statistics in this Update.
Abstract: 1. About These Statistics…e70 2. Cardiovascular Diseases…e72 3. Coronary Heart Disease, Acute Coronary Syndrome, and Angina Pectoris…e89 4. Stroke…e99 5. High Blood Pressure…e111 6. Congenital Cardiovascular Defects…e116 7. Heart Failure…e119 8. Other Cardiovascular Diseases…e122 9. Risk Factor: Smoking/Tobacco Use…e128 10. Risk Factor: High Blood Cholesterol and Other Lipids…e132 11. Risk Factor: Physical Inactivity…e136 12. Risk Factor: Overweight and Obesity…e139 13. Risk Factor: Diabetes Mellitus…e143 14. End-Stage Renal Disease and Chronic Kidney Disease…e149 15. Metabolic Syndrome…e151 16. Nutrition…e153 17. Quality of Care…e155 18. Medical Procedures…e159 19. Economic Cost of Cardiovascular Diseases…e162 20. At-a-Glance Summary Tables…e164 21. Glossary and Abbreviation Guide…e168 Writing Group Disclosures…e171 Appendix I: List of Statistical Fact Sheets: http://www.americanheart.org/presenter.jhtml?identifier=2007 We thank Drs Robert Adams, Philip Gorelick, Matt Wilson, and Philip Wolf (members of the Statistics Committee or Stroke Statistics Subcommittee); Brian Eigel; Gregg Fonarow; Kathy Jenkins; Gail Pearson; and Michael Wolz for their valuable comments and contributions. We would like to acknowledge Tim Anderson and Tom Schneider for their editorial contributions and Karen Modesitt for her administrative assistance. # 1. About These Statistics {#article-title-2} The American Heart Association (AHA) works with the Centers for Disease Control and Prevention’s National Center for Health Statistics (CDC/NCHS); the National Heart, Lung, and Blood Institute (NHLBI); the National Institute of Neurological Disorders and Stroke (NINDS); and other government agencies to derive the annual statistics in this Update. This chapter describes the most important sources and the types of data we use from them. For more details and an alphabetical list of abbreviations, see Chapter 21 of this document, the Glossary and Abbreviation Guide. The surveys used are:

5,393 citations

Journal ArticleDOI
TL;DR: The statistical update brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update.
Abstract: We thank Drs Sean Coady, Eric L. Ding, Brian Eigel, Gregg C. Fonarow, Linda Geiss, Cherie James, Michael Mussolino, and Michael Wolz for their valuable comments and contributions. We acknowledge Tim Anderson and Tom Schneider for their editorial contributions, and Karen Modesitt for her administrative assistance. Disclosures ⇓⇓⇓⇓ View this table: Writing Group Disclosures View this table: Writing Group Disclosures, Continued View this table: Writing Group Disclosures, Continued View this table: Writing Group Disclosures, Continued # Summary {#article-title-2} Each year, the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay …

5,019 citations

Journal ArticleDOI
TL;DR: Each year the American Heart Association brings together the most up-to-date statistics on heart disease, stroke, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update.
Abstract: We thank Drs Robert Adams, Gary Friday, Philip Gorelick, and Sylvia Wasserthiel-Smoller, members of Stroke Statistics Subcommittee; Drs Joe Broderick, Brian Eigel, Kimberlee Gauveau, Jane Khoury, Jerry Potts, Jane Newburger, and Kathryn Taubert; and Sean Coady and Michael Wolz for their valuable comments and contributions. We acknowledge Tim Anderson and Tom Schneider for their editorial contributions and Karen Modesitt for her administrative assistance. View this table: Writing Group Disclosures # Summary {#article-title-2} Each year the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media, the lay public, and many others who seek the …

4,962 citations

Journal ArticleDOI
TL;DR: The statistical update brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update.
Abstract: We thank Drs Sean Coady, Eric L. Ding, Brian Eigel, Gregg C. Fonarow, Linda Geiss, Cherie James, Michael Mussolino, and Michael Wolz for their valuable comments and contributions. We acknowledge Tim Anderson and Tom Schneider for their editorial contributions, and Karen Modesitt for her administrative assistance. Disclosures ⇓⇓⇓⇓ View this table: Writing Group Disclosures View this table: Writing Group Disclosures, Continued View this table: Writing Group Disclosures, Continued View this table: Writing Group Disclosures, Continued # Summary {#article-title-2} Each year, the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay …

4,003 citations