46 results on '"Waters, David D."'
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2. Contributors
- Author
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Abraham, William T., primary, Abrams, Jonathan, additional, Aklog, Lishan, additional, Albert, Michelle A., additional, Antman, Elliott M., additional, Anyanwu, Anelechi, additional, Arora, Rishi, additional, Bakris, George L., additional, Bates, Eric R., additional, Bermudez, Edmund A., additional, Cabell, Christopher H., additional, Calhoun, David A., additional, Califf, Robert M., additional, Callans, David J., additional, Chrysant, George, additional, Cohn, Jay N., additional, Colucci, Wilson S., additional, Couper, Gregory S., additional, Dangas, George D., additional, Danik, Jacqueline Suk, additional, Davidson, Michael H., additional, DiMarco, John P., additional, Drexler, Helmut, additional, Dzau, Victor J., additional, Ellis, Stephen G., additional, Falk, Rodney H., additional, Falkner, Bonita, additional, Fang, James C., additional, Ferguson, John D., additional, Forbess, Lisa W., additional, Fox, Keith A.A., additional, Freedman, Jane, additional, Frisch, Daniel R., additional, Frishman, William H., additional, Froelicher, Victor F., additional, Gaasch, William H., additional, Gehr, Todd W., additional, Giugliano, Robert P., additional, Givertz, Michael M., additional, Gordon, Bruce R., additional, Gulliver, Gene A., additional, Hoit, Brian D., additional, Hsue, Priscilla Y., additional, Hudgins, Lisa Cooper, additional, Jacobson, Jason T., additional, Kadish, Alan H., additional, Karha, Juhana, additional, Katakam, Radhika, additional, Khosla, Nitin, additional, Krousel-Wood, Marie, additional, Kupersmith, Joel, additional, Kushner, Frederick G., additional, Landzberg, Michael J., additional, Lincoff, A. Michael, additional, Maisel, William H, additional, Mangrum, J. Michael, additional, Martucci, Giuseppi, additional, Materson, Barry J., additional, Mathier, Michael A., additional, McManus, Kathy, additional, Meadows, Judith, additional, Melo, Luis G., additional, Mullany, Charles J., additional, Mullen, Mary, additional, Muni, Neal I., additional, Murali, Srinivas, additional, Myers, Jonathan N., additional, Napolitano, Carlo, additional, Nattel, Stanley, additional, Newby, David E., additional, Nishizaka, Mari K., additional, Ooi, Oon C., additional, Oparil, Suzanne, additional, Peterson, Gail E., additional, Priori, Silvia G., additional, Reimold, Sharon C., additional, Rihal, Charanjit S., additional, Sacks, Frank M., additional, Saltman, Adam E., additional, Schroeder, John, additional, Schwartz, Gary L., additional, Shirazi, Farshad, additional, Sica, Domenic A., additional, Stevenson, Lynne W., additional, Stone, Neil J., additional, Sweitzer, Nancy K., additional, Townsend, Raymond R., additional, Umans, Jason G., additional, Velazquez, Eric J., additional, Ward, Christopher A., additional, Washam, Jeffrey B., additional, Waters, David D., additional, Weber, Michael A., additional, Whelton, Paul K., additional, Wiviott, Stephen D., additional, Wollert, Kai C., additional, Woosley, Raymond L., additional, Young, William F., additional, Zimetbaum, Peter, additional, and Zuckerman, Bram D., additional
- Published
- 2007
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3. Notes From Cardiology Clinic: Cinderella's Electronic Medical Record.
- Author
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Waters DD
- Subjects
- California, Female, Humans, Male, Middle Aged, Ambulatory Care Facilities statistics & numerical data, Cardiology statistics & numerical data, Electronic Health Records statistics & numerical data
- Published
- 2021
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4. Notes From Cardiology Clinic: You Can't Ride With the Cops, But Cheer for the Robbers.
- Author
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Waters DD
- Subjects
- Health Inequities, Heart Failure, Humans, Physician-Patient Relations, Prisoners
- Abstract
Competing Interests: Disclosures The author has no conflicts of interest to disclose.
- Published
- 2021
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5. Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial.
- Author
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Tardif JC, Bouabdallaoui N, L'Allier PL, Gaudet D, Shah B, Pillinger MH, Lopez-Sendon J, da Luz P, Verret L, Audet S, Dupuis J, Denault A, Pelletier M, Tessier PA, Samson S, Fortin D, Tardif JD, Busseuil D, Goulet E, Lacoste C, Dubois A, Joshi AY, Waters DD, Hsue P, Lepor NE, Lesage F, Sainturet N, Roy-Clavel E, Bassevitch Z, Orfanos A, Stamatescu G, Grégoire JC, Busque L, Lavallée C, Hétu PO, Paquette JS, Deftereos SG, Levesque S, Cossette M, Nozza A, Chabot-Blanchet M, Dubé MP, Guertin MC, and Boivin G
- Subjects
- Administration, Oral, Ambulatory Care methods, Ambulatory Care statistics & numerical data, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents adverse effects, Double-Blind Method, Drug Monitoring methods, Female, Hospitalization statistics & numerical data, Humans, Intention to Treat Analysis, Male, Middle Aged, Outcome Assessment, Health Care, Risk Assessment, SARS-CoV-2 isolation & purification, COVID-19 diagnosis, COVID-19 epidemiology, Colchicine administration & dosage, Colchicine adverse effects, COVID-19 Drug Treatment
- Abstract
Background: Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission., Methods: The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0·5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97·9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants., Findings: Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53·9% women; median age 54·0 years, IQR 47·0-61·0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4·7%) of 2235 patients in the colchicine group and 131 (5·8%) of 2253 patients in the placebo group (odds ratio [OR] 0·79, 95·1% CI 0·61-1·03; p=0·081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4·6%) of 2075 patients in the colchicine group and 126 (6·0%) of 2084 patients in the placebo group (OR 0·75, 0·57-0·99; p=0·042). Serious adverse events were reported in 108 (4·9%) of 2195 patients in the colchicine group and 139 (6·3%) of 2217 patients in the placebo group (p=0·051); pneumonia occurred in 63 (2·9%) of 2195 patients in the colchicine group and 92 (4·1%) of 2217 patients in the placebo group (p=0·021). Diarrhoea was reported in 300 (13·7%) of 2195 patients in the colchicine group and 161 (7·3%) of 2217 patients in the placebo group (p<0·0001)., Interpretation: In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended., Funding: The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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6. The association between lipid levels and leukocyte count: A cross-sectional and longitudinal analysis of three large cohorts.
- Author
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Sawant S, Tucker B, Senanayake P, Waters DD, Patel S, Rye KA, Ong KL, and Cochran BJ
- Abstract
Background: Relationships between dyslipidaemia and leukocyte counts have been investigated in several studies, demonstrating limited evidence of associations in humans. As such, studying a diverse range of cohorts will ensure evidence is robust. This study focused on investigating cross-sectional and longitudinal relationships in three large-scale cohorts., Methods: The cross-sectional analysis included a total of 27,566 participants with valid data on lipid measures and leukocyte counts from three study cohorts: National Health and Nutrition Survey (NHANES), Korean National Health and Nutrition Survey (KNHANES) and Treating to New Targets (TNT) trial. The longitudinal analysis included 9323 participants with valid data on lipid measures and leukocyte counts at baseline and one year with statin treatment. Associations between lipid levels and leukocyte counts were analysed by multivariable linear regression and adjusted for basic demographic and cardiovascular risk factors., Results: Cross-sectional data from NHANES demonstrated the association of lower high-density lipoprotein (HDL) cholesterol and higher triglycerides with higher leukocyte count (0.9% lower and 0.3% higher count per 10 mg/dL increase in HDL cholesterol and triglycerides respectively, both p < 0.001). Similar trends were found in TNT trial (both p < 0.001), but not in KNHANES. In the TNT trial, 10 mg/dL increase in triglycerides over one year was also associated with a 0.09 × 10
3 /μL increase in leukocyte count over the same period., Conclusions: The findings of this study are consistent with those of previous human studies, supporting weak yet noteworthy associations between dyslipidaemia and leukocytosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)- Published
- 2021
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7. Notes From Cardiology Clinic: Mitral Stenosis and Racial Discordance.
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Waters DD
- Subjects
- Humans, Physician-Patient Relations ethics, Racism ethics, Racism trends, Cardiology trends, Healthcare Disparities ethnology, Mitral Valve Stenosis ethnology, Mitral Valve Stenosis therapy, Racism prevention & control
- Published
- 2021
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8. Notes From Cardiology Clinic: Trouble for Tongans.
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Waters DD
- Subjects
- Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Preventive Health Services, Tonga epidemiology, United States ethnology, Heart Disease Risk Factors, Heart Failure epidemiology, Heart Failure etiology, Heart Failure prevention & control, Obesity, Morbid complications, Obesity, Morbid ethnology, Obesity, Morbid genetics
- Published
- 2021
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9. Notes From Cardiology Clinic: The Heartbreaking Risk Factor We Overlook.
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Waters DD
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- Heart Disease Risk Factors, Humans, Patient Care Management, Psychosomatic Medicine, Heart Diseases diagnosis, Heart Diseases psychology, Stress Disorders, Post-Traumatic diagnosis, Stress Disorders, Post-Traumatic physiopathology, War-Related Injuries physiopathology, War-Related Injuries psychology
- Published
- 2020
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10. Will Colchicine Soon Be Part of Primary and Secondary Cardiovascular Prevention?
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Samuel M and Waters DD
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- Colchicine, Humans, Male, Secondary Prevention, Cardiovascular System, Coronary Artery Disease, Gout
- Published
- 2020
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11. Notes From Cardiology Clinic: Health Care Heroine, Unpaid and Unappreciated.
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Waters DD
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- Female, Humans, Male, United States, Ambulatory Care Facilities economics, Cardiology, Delivery of Health Care economics, Health Care Costs
- Published
- 2020
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12. Notes From Cardiology Clinic: Brittle Bones and Blue Sclerae.
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Waters DD
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- Adolescent, Heart Failure diagnosis, Humans, Male, Osteogenesis Imperfecta complications, Cardiology, Heart Failure etiology, Hospitals, Osteogenesis Imperfecta diagnosis
- Published
- 2020
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13. Erratum to "Notes From Cardiology Clinic: The Patients We Dislike": Can J Cardiol 36 (2020) 157-158.
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Waters DD
- Abstract
The Publisher regrets that this article is an accidental duplication of an article that has already been published in Can J Cardiol 36 (2020) 453-454, https://doi.org/10.1016/j.cjca.2019.08.034. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)
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- 2020
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14. Notes From the Cardiology Clinic: Facing Down the Dragons of Health Anxiety.
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Waters DD
- Subjects
- Attitude to Health, Humans, Ambulatory Care ethics, Ambulatory Care methods, Ambulatory Care psychology, Anxiety physiopathology, Anxiety prevention & control, Illness Behavior ethics, Myocardial Ischemia psychology, Myocardial Ischemia therapy, Physician-Patient Relations ethics, Quality of Life
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- 2020
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15. When Diastole Lets You Down: Clinical Relevance of a Widened Pulse Pressure.
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Tannenbaum J, Bittner V, and Waters DD
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- Blood Pressure, Diastole, Humans, Systole, Hypertension, Percutaneous Coronary Intervention
- Published
- 2020
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16. Notes From Cardiology Clinic: The Patients We Dislike.
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Waters DD
- Subjects
- Humans, Attitude of Health Personnel, Cardiology, Patients, Sex Offenses
- Published
- 2020
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17. Notes From Cardiology Clinic: Woman, Lost During Follow-up.
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Waters DD
- Subjects
- Aged, Aged, 80 and over, Cardiovascular Diseases epidemiology, Female, Follow-Up Studies, Humans, Incidence, Lost to Follow-Up, Postmenopause, United States epidemiology, Cardiology, Cardiovascular Diseases prevention & control, Hormone Replacement Therapy methods, Primary Prevention methods, Women's Health
- Published
- 2019
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18. Notes From Cardiology Clinic: When Our Responsibilities Extend Beyond the Patient.
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Waters DD
- Subjects
- Cardiology ethics, Social Responsibility
- Published
- 2019
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19. Improving Statin Noncompliance: If You Build It, Will They Come?
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Sparrow RT, Ferreira-Legere L, Udell JA, and Waters DD
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- Alberta, Cholesterol, LDL, Humans, Cardiovascular Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia
- Published
- 2019
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20. Cholesterol Lowering Guidelines: From Whence We Came and Where We Are Now.
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Waters DD
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- Humans, Practice Guidelines as Topic, Anticholesteremic Agents pharmacology, Cardiovascular Diseases prevention & control, Secondary Prevention methods, Secondary Prevention standards
- Abstract
Treatment guidelines have proliferated in cardiology, although most guideline recommendations are not supported by clinical trial evidence. What is considered to be a normal cholesterol level has progressively declined over the past 50 years, with the increasing realization that "normal" is far from optimal and that lower is better. The first important United States and Canadian cholesterol guidelines were published in 1988, and recommended diet for 6 months to be followed by consideration of bile acid sequestrants or nicotinic acid. Over the ensuing 25 years guidelines have changed rapidly and dramatically in response to a large number of definitive clinical trials, usually with statins. Low-density lipoprotein cholesterol targets have moved progressively lower, and in some guidelines, have been abandoned entirely. The concept of selecting patients for treatment according to the absolute risk reduction expected from treatment on the basis of clinical trial data seems to be a rational approach. For secondary prevention, some patients are still untreated or undertreated, presenting an opportunity for improving outcomes., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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21. Lipid Abnormalities in Persons Living With HIV Infection.
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Waters DD and Hsue PY
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- Humans, Medication Therapy Management, Anti-Retroviral Agents pharmacology, Cardiovascular Diseases immunology, Cardiovascular Diseases metabolism, Cardiovascular Diseases prevention & control, HIV Infections drug therapy, HIV Infections metabolism, Lipid Metabolism drug effects, Lipid Metabolism immunology
- Abstract
Lipid abnormalities are prevalent among persons living with HIV infection and contribute to increasing the risk of cardiovascular events. Antiretroviral therapy (ART) is associated with lipid abnormalities, most commonly hypertriglyceridemia, but also increases in low-density lipoprotein cholesterol and total cholesterol. Different classes of ART, and different drugs within classes, have differing effects on lipid levels, but in general newer drugs have more favourable effects compared with older ones. Low-level inflammation and chronic immune activation act on lipids through a variety of mechanisms to make them more atherogenic. As a consequence, risk is higher than would be expected for any given cholesterol level. Clinical outcome trials of cholesterol-lowering therapies have not yet been completed in people living with HIV, so that treatment decisions depend on extrapolation from studies in uninfected populations. Traditional risk assessment tools underestimate cardiovascular risk in individuals with HIV. Statins are the mainstay of lipid-lowering drug treatment; however, drug-drug interactions with ART must be considered. Simvastatin and lovastatin are contraindicated in patients taking protease inhibitors, and the dose of atorvastatin and rosuvastatin should be limited to 40 mg and 10 mg/d with some ART combinations. Switching from older forms of ART to lipid-friendly newer ones is a useful strategy as long as virologic suppression is maintained, but adding a statin lowers low-density lipoprotein cholesterol more effectively. Studies indicate that lipid abnormalities are not treated as aggressively in individuals living with HIV as they are in uninfected people, making this an opportunity to improve care., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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22. Introduction to Cardiovascular Issues in HIV.
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Waters DD and Hsue PY
- Subjects
- Cardiovascular System immunology, Cardiovascular System physiopathology, Humans, Risk Factors, Anti-HIV Agents pharmacology, Cardiovascular Diseases classification, Cardiovascular Diseases etiology, Cardiovascular Diseases immunology, Cardiovascular Diseases prevention & control, HIV Infections complications, HIV Infections physiopathology, HIV Infections therapy, Inflammation immunology, Inflammation physiopathology
- Published
- 2019
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23. Variations in time to benefit among clinical trials of cholesterol-lowering drugs.
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Barter PJ and Waters DD
- Subjects
- Cholesterol, LDL blood, Clinical Trials as Topic, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hypercholesterolemia pathology, Risk Assessment, Anticholesteremic Agents therapeutic use, Hypercholesterolemia drug therapy
- Abstract
Background: Time to benefit (TTB) in clinical trials of cholesterol-lowering drugs is important because it may provide a clue as to the potential mechanism of action of the drug, it is helpful in determining when to stop a trial for futility, and it may inform treatment decisions in subjects with reduced life expectancy., Objective: To compare TTB among clinical trials of cholesterol-lowering drugs., Methods: We examined TTB in 24 trials of cholesterol-lowering drugs with positive outcomes. Benefit curves were constructed by subtracting the curve for a placebo or comparator drug from the curve for active treatment., Results: TTB ranged from 1 to 30 (mean 13.1) months, being shorter in trials of statins (n = 17) compared to nonstatins (n = 7), 10.3 vs 20.0 months. Among statin trials, TTB was shorter with atorvastatin (n = 6) than in trials with other statins (n = 11), 4.75 compared to 11.4 months., Conclusions: TTB is variable among trials of cholesterol-lowering drugs, being shorter with statin compared to nonstatin drugs. TTB is shorter with atorvastatin than with other statins. For trials of new cholesterol-lowering drugs, outcome curves that do not separate for up to 30 months do not preclude eventual benefit., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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24. Lipids, inflammation, and chronic kidney disease: a SHARP perspective.
- Author
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Waters DD and Vogt L
- Subjects
- Cardiovascular Diseases, Cholesterol, LDL, Drug Therapy, Combination, Humans, Inflammation, Lipids, Renal Insufficiency, Chronic, Simvastatin, Treatment Outcome, Anticholesteremic Agents, Azetidines
- Abstract
Accumulating evidence indicates that inflammation plays a role in the initiation and progression of chronic kidney disease. In the Study of Heart and Renal Protection (SHARP) trial, higher baseline C-reactive protein and higher baseline low-density lipoprotein cholesterol levels were both associated with a higher risk of cardiovascular events, but higher baseline C-reactive protein levels were also associated with a higher risk of nonvascular events. Simvastatin/ezetimibe reduced cardiovascular events independent of baseline C-reactive protein levels. However, this observation does not exclude inflammation as a causal factor for cardiovascular disease development in chronic kidney disease patients., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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25. Visit-to-visit variability of lipid measurements as predictors of cardiovascular events.
- Author
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Waters DD, Bangalore S, Fayyad R, DeMicco DA, Laskey R, Melamed S, and Barter PJ
- Subjects
- Adult, Aged, Anticholesteremic Agents therapeutic use, Atorvastatin therapeutic use, Cardiovascular Diseases diagnosis, Cardiovascular Diseases prevention & control, Coronary Artery Disease diagnosis, Coronary Artery Disease prevention & control, Female, Follow-Up Studies, Humans, Male, Middle Aged, Predictive Value of Tests, Prognosis, Risk Factors, Cardiovascular Diseases blood, Cholesterol, HDL blood, Cholesterol, LDL blood, Coronary Artery Disease blood, Triglycerides blood
- Abstract
Background: Higher visit-to-visit variability in risk factors such as blood pressure and low-density lipoprotein (LDL)-cholesterol are associated with an increase in cardiovascular (CV) events., Objective: The purpose of this study was to determine whether variability in high-density lipoprotein cholesterol (HDL-C) and triglyceride levels predicted coronary and CV events in a clinical trial population with known coronary disease., Methods: We assessed intraindividual variability in fasting high-density lipoprotein (HDL)-cholesterol, triglyceride, and LDL-cholesterol measurements among 9572 patients in the Treating to New Targets trial and correlated the results with coronary events over a median follow-up of 4.9 years., Results: In the fully adjusted Cox model, 1 standard deviation of average successive variability, defined as the average absolute difference between successive values, was associated with an increased risk of a coronary event for HDL-cholesterol (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.11-1.21, P < .0001), for triglycerides (HR 1.09, 95% CI 1.04-1.15, P = .0005), and for LDL-cholesterol (HR 1.14, 95% CI 1.09-1.19, P < .0001). Similar results were found for the 3 other measures of variability, standard deviation, coefficient of variability, and variability independent of the mean. Similar results were seen for CV events, stroke, and nonfatal myocardial infarction. Higher variability in triglyceride and LDL-cholesterol, but not HDL-cholesterol, was predictive of incident diabetes. The correlation among the variability of the 3 lipid measurements was weak., Conclusion: Visit-to-visit variability in fasting measurements of HDL-cholesterol, triglycerides, and LDL-cholesterol are predictive of coronary events, CV events, and for triglyceride and low-density lipoprotein cholesterol variability, incident diabetes. The mechanisms accounting for these associations remain to be determined., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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26. Effect of atorvastatin, cholesterol ester transfer protein inhibition, and diabetes mellitus on circulating proprotein subtilisin kexin type 9 and lipoprotein(a) levels in patients at high cardiovascular risk.
- Author
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Arsenault BJ, Petrides F, Tabet F, Bao W, Hovingh GK, Boekholdt SM, Ramin-Mangata S, Meilhac O, DeMicco D, Rye KA, Waters DD, Kastelein JJP, Barter P, and Lambert G
- Subjects
- Aged, Cardiovascular Diseases complications, Cholesterol, LDL blood, Diabetes Mellitus, Type 2 complications, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Placebo Effect, Quinolines therapeutic use, Risk Factors, Treatment Outcome, Atorvastatin therapeutic use, Cardiovascular Diseases drug therapy, Cholesterol Ester Transfer Proteins antagonists & inhibitors, Diabetes Mellitus, Type 2 pathology, Lipoprotein(a) blood, Proprotein Convertase 9 blood
- Abstract
Background: Proprotein subtilisin kexin type 9 (PCSK9) and lipoprotein (a) [Lp(a)] levels are causative risk factors for coronary heart disease., Objectives: The objective of the study was to determine the impact of lipid-lowering treatments on circulating PCSK9 and Lp(a)., Methods: We measured PCSK9 and Lp(a) levels in plasma samples from Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events trial patients with coronary heart disease and/or type II diabetes (T2D) mellitus. Patients received atorvastatin, which was titrated (10, 20, 40, or 80 mg/d) to achieve low-density lipoprotein cholesterol levels <100 mg/dL (baseline) and were subsequently randomized either to atorvastatin + torcetrapib, a cholesterol ester transfer protein inhibitor, or to atorvastatin + placebo., Results: At baseline, both plasma PCSK9 and Lp(a) were dose-dependently increased with increasing atorvastatin doses. Compared with patients without T2D, those with T2D had higher PCSK9 (357 ± 123 vs 338 ± 115 ng/mL, P = .0012) and lower Lp(a) levels (28 ± 32 vs 32 ± 33 mg/dL, P = .0005). Plasma PCSK9 levels significantly increased in patients treated with torcetrapib (+13.1 ± 125.3 ng/mL [+3.7%], P = .005), but not in patients treated with placebo (+2.6 ± 127.9 ng/mL [+0.7%], P = .39). Plasma Lp(a) levels significantly decreased in patients treated with torcetrapib (-3.4 ± 10.7 mg/dL [-11.1%], P < .0001), but not in patients treated with placebo (+0.3 ± 9.4 mg/dL [+0.1%], P = .92)., Conclusion: In patients at high cardiovascular disease risk, PCSK9 and Lp(a) are positively and dose-dependently correlated with atorvastatin dosage, whereas the presence of T2D is associated with higher PCSK9 but lower Lp(a) levels. Cholesterol ester transfer protein inhibition with torcetrapib slightly increases PCSK9 levels and decreases Lp(a) levels., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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27. Taking Hockey to Heart: Potential Coronary Risks of Watching Exciting Games.
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Waters DD and Nattel S
- Subjects
- Canada epidemiology, Humans, Morbidity trends, Risk Factors, Cardiovascular Diseases epidemiology, Hockey, Risk Assessment
- Published
- 2017
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28. The Evolution of Myocardial Infarction: When the Truths We Hold To Be Self-Evident No Longer Have Evidence.
- Author
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Waters DD and Bangalore S
- Subjects
- Humans, Myocardial Infarction
- Published
- 2017
- Full Text
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29. An Evidence-Based Guide to Cholesterol-Lowering Guidelines.
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Waters DD and Boekholdt SM
- Subjects
- Anticholesteremic Agents therapeutic use, Humans, Hypercholesterolemia blood, Cholesterol blood, Evidence-Based Medicine, Hypercholesterolemia drug therapy, Practice Guidelines as Topic
- Abstract
Since 2014, guidelines for the management of lipid disorders to reduce cardiovascular (CV) events have been updated in the United States, the United Kingdom, Europe, and Canada. Some of these guidelines are almost entirely evidence-based whereas others are a mix of evidence and expert opinion. Guidelines differ on such simple questions as to whether blood samples should be fasting or nonfasting, and whether low-density lipoprotein cholesterol (LDL-C) or another lipid parameter should be the primary focus of treatment. Different risk assessment tools are recommended by different guidelines. Lifetime risk is highlighted in some guidelines, with the suggestion that earlier treatment will reduce lifetime risk in younger people even when short-term risk is low. Some guidelines have numerical treatment targets that differ according to level of risk, while others eschew targets but recommend statins at high or moderate intensity to reduce LDL-C by ≥ 50% or 30%-50%, respectively. Statins are the backbone of therapy in all guidelines. Ezetimibe produced a 6.4% relative risk reduction in the only large clinical outcomes trial in which it was tested, and is recommended for high-risk patients with an inadequate response to statins, despite the high number needed to treat to prevent 1 CV event. Proprotein convertase subtilisin/kexin 9 inhibitors lack outcome data to support their use, but are approved for patients with familial hypercholesterolemia or clinical atherosclerotic CV disease who require additional LDL-C lowering beyond statins. All these new guidelines are aimed at improving the problem of undertreatment of high-risk groups, leading to better outcomes for these patients., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
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30. The Rise and Fall of Tuberculosis and Atherosclerosis: First There Is a Mountain….
- Author
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Waters DD
- Subjects
- Humans, Atherosclerosis, Tuberculosis
- Published
- 2017
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31. Predicting Prognosis in Acute Coronary Syndromes: Makeover Time for TIMI and GRACE?
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Waters DD and Arsenault BJ
- Subjects
- Humans, Prognosis, Risk Assessment, Acute Coronary Syndrome, Angina, Unstable
- Published
- 2016
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32. Performance Deficiencies in the Treatment of ST-Elevation Myocardial Infarction in Québec: "Tis But a Part We See, and Not a Whole".
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Azar RR, Kadri Z, and Waters DD
- Subjects
- Humans, Quebec, ST Elevation Myocardial Infarction, Electrocardiography, Myocardial Infarction
- Published
- 2016
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33. Tribulations of Recent Cardiology Trials, the Audacity of Hope, and HOPE-3.
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Waters DD and Chau KH
- Subjects
- Female, Humans, Male, Benzimidazoles administration & dosage, Blood Pressure physiology, Cardiovascular Diseases prevention & control, Cholesterol, LDL blood, Hydrochlorothiazide administration & dosage, Primary Prevention methods, Rosuvastatin Calcium administration & dosage, Tetrazoles administration & dosage
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- 2016
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34. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.
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Swerdlow DI, Preiss D, Kuchenbaecker KB, Holmes MV, Engmann JE, Shah T, Sofat R, Stender S, Johnson PC, Scott RA, Leusink M, Verweij N, Sharp SJ, Guo Y, Giambartolomei C, Chung C, Peasey A, Amuzu A, Li K, Palmen J, Howard P, Cooper JA, Drenos F, Li YR, Lowe G, Gallacher J, Stewart MC, Tzoulaki I, Buxbaum SG, van der A DL, Forouhi NG, Onland-Moret NC, van der Schouw YT, Schnabel RB, Hubacek JA, Kubinova R, Baceviciene M, Tamosiunas A, Pajak A, Topor-Madry R, Stepaniak U, Malyutina S, Baldassarre D, Sennblad B, Tremoli E, de Faire U, Veglia F, Ford I, Jukema JW, Westendorp RG, de Borst GJ, de Jong PA, Algra A, Spiering W, Maitland-van der Zee AH, Klungel OH, de Boer A, Doevendans PA, Eaton CB, Robinson JG, Duggan D, Kjekshus J, Downs JR, Gotto AM, Keech AC, Marchioli R, Tognoni G, Sever PS, Poulter NR, Waters DD, Pedersen TR, Amarenco P, Nakamura H, McMurray JJ, Lewsey JD, Chasman DI, Ridker PM, Maggioni AP, Tavazzi L, Ray KK, Seshasai SR, Manson JE, Price JF, Whincup PH, Morris RW, Lawlor DA, Smith GD, Ben-Shlomo Y, Schreiner PJ, Fornage M, Siscovick DS, Cushman M, Kumari M, Wareham NJ, Verschuren WM, Redline S, Patel SR, Whittaker JC, Hamsten A, Delaney JA, Dale C, Gaunt TR, Wong A, Kuh D, Hardy R, Kathiresan S, Castillo BA, van der Harst P, Brunner EJ, Tybjaerg-Hansen A, Marmot MG, Krauss RM, Tsai M, Coresh J, Hoogeveen RC, Psaty BM, Lange LA, Hakonarson H, Dudbridge F, Humphries SE, Talmud PJ, Kivimäki M, Timpson NJ, Langenberg C, Asselbergs FW, Voevoda M, Bobak M, Pikhart H, Wilson JG, Reiner AP, Keating BJ, Hingorani AD, and Sattar N
- Subjects
- Aged, Body Mass Index, Cholesterol, HDL metabolism, Cholesterol, LDL metabolism, Female, Genetic Testing, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Risk Factors, Body Weight genetics, Diabetes Mellitus, Type 2 genetics, Hydroxymethylglutaryl CoA Reductases genetics, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Polymorphism, Single Nucleotide genetics
- Abstract
Background: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target., Methods: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis., Findings: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials)., Interpretation: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition., Funding: The funding sources are cited at the end of the paper., (Copyright © 2015 Swerdlow et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2015
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35. The past and future of heart institutes: having moved beyond the one-trick pony.
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Waters DD
- Subjects
- Academies and Institutes, Humans, Cardiology methods, Delivery of Health Care methods, Heart Diseases therapy
- Published
- 2014
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36. Looking for coronary disease in patients with atrial fibrillation.
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Kohli P and Waters DD
- Subjects
- Female, Humans, Male, Atrial Fibrillation epidemiology, Coronary Artery Disease diagnosis, Electrocardiography
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- 2014
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37. Papering over the cracks: meta-analysis to define the role of percutaneous coronary intervention in patients with stable angina.
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Waters DD
- Subjects
- Humans, Angina, Stable therapy, Percutaneous Coronary Intervention, Vasodilator Agents therapeutic use
- Published
- 2013
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38. Utility of biomarkers and imaging in the development of drugs for the treatment of coronary atherosclerosis.
- Author
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Waters DD
- Subjects
- Carotid Intima-Media Thickness, Humans, Anticholesteremic Agents therapeutic use, Biomarkers blood, Coronary Artery Disease blood, Coronary Artery Disease diagnosis, Coronary Artery Disease drug therapy, Diagnostic Imaging statistics & numerical data, Hypolipidemic Agents therapeutic use
- Abstract
Biomarkers and imaging trials have often been used as guideposts in the development of drugs for atherosclerosis. This article explores the role of biomarkers and imaging trials in the development of 4 drugs: rimonabant, torcetrapib, ezetimibe, and niacin. Rimonabant, a selective cannabinoid-1 receptor, causes weight loss and exerts favourable effects on lipid biomarkers. An intracoronary ultrasound study showed no effect for the primary but significant benefit for the secondary end point. A large clinical outcomes trial was halted when it became apparent that the drug caused serious psychiatric side effects, including suicide. Torcetrapib, a cholesteryl ester transfer protein inhibitor, lowers low-density lipoprotein (LDL) cholesterol and induces a marked increase in high-density lipoprotein (HDL) cholesterol. However, a large clinical outcomes trial was halted very prematurely due to a 58% increase in all-cause mortality. Neutral imaging studies were reported later. Ezetimibe lowers low density lipoprotein cholesterol but did not reduce carotid intima-media thickness, and there is as yet no clinical trial evidence that it reduces cardiovascular events after a decade on the market. Niacin exerts favourable effects on lipid biomarkers and has shown regression of atherosclerosis in small carotid imaging trials, but did not reduce events in a recent clinical trial that was stopped early due to a lack of efficacy. In summary, favourable effects on lipid biomarkers often do not translate into clinical benefit, and imaging trials, which focus on a narrow measurement of atherosclerosis, are also often not helpful., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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39. A comparison of non-HDL and LDL cholesterol goal attainment in a large, multinational patient population: the Lipid Treatment Assessment Project 2.
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Santos RD, Waters DD, Tarasenko L, Messig M, Jukema JW, Chiang CW, Ferrieres J, and Foody JM
- Subjects
- Adult, Aged, Canada, Europe, Female, Humans, Latin America, Male, Middle Aged, Risk Factors, Treatment Outcome, Triglycerides blood, United States, Cholesterol, HDL blood, Cholesterol, LDL blood, Coronary Disease drug therapy, Dyslipidemias drug therapy, Hypolipidemic Agents therapeutic use
- Abstract
Objective: This study evaluated the success in attaining non-HDL-cholesterol (non-HDL-C) goals in the multinational L-TAP 2 study., Methods: 9955 patients ≥20 years of age with dyslipidemia on stable lipid-lowering therapy were enrolled from nine countries., Results: Success rates for non-HDL-C goals were 86% in low, 70% in moderate, and 52% in high-risk patients (63% overall). In patients with triglycerides of >200 mg/dL success rates for non-HDL-C goals were 35% vs. 69% in those with ≤200 mg/dL (p < 0.0001). Among patients attaining their LDL-C goal, 18% did not attain their non-HDL-C goal. In those with coronary disease and at least two risk factors, only 34% and 30% attained respectively their non-HDL-C and LDL-C goals. Rates of failure in attaining both LDL-C and non-HDL-C goals were highest in Latin America., Conclusions: Non-HDL-C goal attainment lagged behind LDL-C goal attainment; this gap was greatest in higher-risk patients., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2012
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40. Statins before stents: does an ounce of prevention improve outcomes?
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Frey P and Waters DD
- Subjects
- Atorvastatin, Biomarkers blood, Carotid Artery Diseases blood, Carotid Artery Diseases prevention & control, Creatine Kinase, MB Form blood, Evidence-Based Medicine, Heptanoic Acids administration & dosage, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Preoperative Care, Pyrroles administration & dosage, Risk Assessment, Risk Factors, Stroke prevention & control, Treatment Outcome, Troponin I blood, Troponin T blood, Carotid Artery Diseases drug therapy, Carotid Artery Diseases surgery, Heptanoic Acids therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Pyrroles therapeutic use, Stents
- Published
- 2010
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41. Exploring new indications for statins beyond atherosclerosis: Successes and setbacks.
- Author
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Waters DD
- Subjects
- Humans, Alzheimer Disease prevention & control, Aortic Valve Stenosis drug therapy, Atherosclerosis drug therapy, Heart Failure drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
- Abstract
Statins have been shown to reduce cardiovascular events across a broad spectrum of patients at risk, irrespective of baseline LDL-cholesterol levels. In a meta-analysis of 14 statin trials involving more than 90,000 participants, statin therapy reduced the 5-year incidence of cardiovascular events by about 20% for each mmol/L of LDL-cholesterol reduction. The results of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study suggest that the degree of reduction in Japanese subjects may be greater than this for the same degree of LDL-cholesterol reduction. Given the success of statins in preventing cardiovascular events, it is not surprising that they have been tested in a variety of related conditions, three of which are discussed in this article. Heart failure is characterized by inflammation, endothelial dysfunction and neurohumeral activation, conditions that are ameliorated by statin therapy. The Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) showed no significant benefit of rosuvastatin upon the primary endpoint, cardiovascular death, myocardial infarction and stroke. However, subgroups identified by the biomarkers plasma amino-terminal pro-brain natriuretic and C-reactive protein showed a reduction in events. Aortic stenosis and atherosclerosis share common risk factors, including hypertension and hypercholesterolemia. Although non-randomized cohort studies have suggested that statins slow the progression of aortic stenosis, this was not shown in either of the two randomized placebo-controlled trials testing this hypothesis. Similarly, Alzheimer's disease shares many risk factors with atherosclerosis, and several observational studies have reported a lower risk of developing this condition in patients taking statins. However, two recently completed clinical trials indicate that neither atorvastatin nor simvastatin slow the progression of early Alzheimer's disease. In conclusion, although statins are effective, established therapy for the prevention of vascular events in patients at risk, they have as yet not proven to be successful for these newer indications., (Copyright 2009 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2010
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42. A winter's tale: report from the First Annual Canadian Biomarkers and Surrogate Endpoints Symposium.
- Author
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Heinonen T, Waters DD, Libby P, and Tardif JC
- Subjects
- Canada, Cardiovascular Diseases blood, Diagnosis, Differential, Echocardiography methods, Endosonography methods, Humans, Magnetic Resonance Imaging methods, Tomography, Emission-Computed, Single-Photon methods, Biomarkers blood, Cardiovascular Diseases diagnosis, Carotid Arteries diagnostic imaging, Congresses as Topic, Coronary Angiography methods, Coronary Vessels diagnostic imaging, Diagnostic Imaging methods
- Published
- 2009
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43. Effects of 1-H-indole-3-glyoxamide (A-002) on concentration of secretory phospholipase A2 (PLASMA study): a phase II double-blind, randomised, placebo-controlled trial.
- Author
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Rosenson RS, Hislop C, McConnell D, Elliott M, Stasiv Y, Wang N, and Waters DD
- Subjects
- Cholesterol blood, Coronary Disease blood, Double-Blind Method, Enzyme Inhibitors adverse effects, Female, Humans, Lipoproteins blood, Male, Middle Aged, Coronary Disease drug therapy, Coronary Disease enzymology, Enzyme Inhibitors therapeutic use, Phospholipases A2, Secretory antagonists & inhibitors, Phospholipases A2, Secretory blood
- Abstract
Background: Secretory phospholipase A(2) (sPLA(2)) enzymes, produced and secreted in human blood vessels and hepatocytes, contribute to the development of atherosclerosis through mechanisms that are both dependent and independent of lipoprotein. We examined the effects of an sPLA(2) inhibitor on enzyme concentration and on plasma lipoproteins and inflammatory biomarkers in patients with coronary heart disease., Methods: Patients aged 18 years and older with stable coronary heart disease from the USA and Ukraine were eligible for enrolment in this phase II, randomised, double-blind, placebo-controlled, parallel-arm, dose-response study. 393 patients were randomly assigned by computer-generated sequence to receive either placebo (n=79) or one of four doses of an sPLA(2) inhibitor, A-002 (1-H-indole-3-glyoxamide; 50 mg [n=79], 100 mg [n=80], 250 mg [n=78], or 500 mg [n=77] twice daily), for 8 weeks. The primary endpoint was the change in sPLA(2) group IIA (sPLA(2)-IIA) concentration or activity from baseline to week 8. Analysis was by modified intention to treat (ITT). The ITT population consisted of all patients who received one dose of study treatment; data for patients who dropped out before the end of the study were carried forward from last observation. This trial is registered with ClinicalTrials.gov, number NCT00455546., Findings: All randomised patients received at least one dose and were included in the ITT population. Data for 45 patients were carried forward from last observation (36 in the A-002 group and nine in the placebo group); the main reason for dropout before completion was because of adverse events. 348 patients reached the primary endpoint (A-002 n=278, placebo n=70). Mean sPLA(2)-IIA concentration fell by 86.7%, from 157 pmol/L to 21 [corrected] pmol/L, in the overall active treatment group, and by 4.8%, from 157 pmol/L to 143 [corrected] pmol/L, in the placebo group (p<0.0001 treatment vs placebo). The reductions in sPLA(2)-IIA concentration in the A-002 groups were dose dependent (ranging from 69.2% in the 50 mg group to 95.8% in the 500 mg group) and differed significantly from placebo (p<0.0001 for all doses). In the 500 mg A-002 treatment group, there was one serious adverse event (exacerbation of underlying chronic obstructive pulmonary disease), but the proportion of patients reporting treatment-emergent adverse events did not differ from placebo. The main side-effects of the drug included headache (n=20), nausea (n=17), and diarrhoea (n=12)., Interpretation: The reductions in sPLA(2)-IIA concentration suggest that A-002 might be an effective anti-atherosclerotic agent.
- Published
- 2009
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44. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study.
- Author
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Deedwania P, Barter P, Carmena R, Fruchart JC, Grundy SM, Haffner S, Kastelein JJ, LaRosa JC, Schachner H, Shepherd J, and Waters DD
- Subjects
- Adult, Aged, Anticholesteremic Agents administration & dosage, Atorvastatin, Cardiovascular Diseases etiology, Cardiovascular Diseases mortality, Cholesterol, LDL drug effects, Coronary Disease blood, Diabetes Complications, Dose-Response Relationship, Drug, Double-Blind Method, Female, Heptanoic Acids administration & dosage, Humans, Male, Metabolic Syndrome blood, Middle Aged, Pyrroles administration & dosage, Risk Factors, Anticholesteremic Agents therapeutic use, Cardiovascular Diseases prevention & control, Cholesterol, LDL blood, Coronary Disease complications, Heptanoic Acids therapeutic use, Metabolic Syndrome complications, Metabolic Syndrome drug therapy, Pyrroles therapeutic use
- Abstract
Background: Despite the prognostic value of metabolic syndrome for predicting cardiovascular events, few trials have investigated the effects of statin therapy on cardiovascular morbidity and mortality in patients with the metabolic syndrome. Our post hoc analysis of the Treating to New Targets (TNT) study assessed whether intensive lowering of low-density lipoprotein cholesterol with high-dose atorvastatin therapy results in cardiovascular benefits for patients with both coronary heart disease and the metabolic syndrome., Methods: The TNT study was a prospective, double blind, parallel-group trial done at 256 sites in 14 countries between April, 1998, and August, 2004, with a median follow-up of 4.9 years. 10,001 patients were enrolled aged 35-75 years with clinically evident coronary heart disease. Our analysis includes 5584 patients with metabolic syndrome based on the 2005 NCEP ATP III criteria. Patients were randomly assigned to receive either atorvastatin 10 mg per day (n=2820) or 80 mg per day (n=2764). The primary outcome measure was time to first major cardiovascular event, defined as death from coronary heart disease, non-fatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or non-fatal stroke., Findings: In patients with coronary heart disease and metabolic syndrome, mean on-treatment low-density lipoprotein cholesterol concentrations at 3 months were 2.6 mmol/L (99.3 mg/dL) with atorvastatin 10 mg, and 1.9 mmol/L (72.6 mg/dL) with atorvastatin 80 mg. At a median follow-up of 4.9 years, major cardiovascular events occurred in 367 (13%) patients receiving atorvastatin 10 mg, compared with 262 (9.5%) receiving atorvastatin 80 mg (hazard ratio 0.71; 95% CI 0.61-0.84; p<0.0001). Irrespective of treatment assignment, significantly more patients with metabolic syndrome (11.3%) had a major cardiovascular event at a median of 4.9 years than those without metabolic syndrome (8.0%; hazard ratio 1.44; 95% CI 1.26-1.64; p<0.0001). This increased risk was significantly reduced by intensive therapy with atorvastatin 80 mg beyond that achieved with atorvastatin 10 mg., Interpretation: These data indicate that patients with coronary heart disease and metabolic syndrome derive incremental benefit from high-dose atorvastatin therapy, irrespective of the presence of diabetes.
- Published
- 2006
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45. Hormone therapy and antioxidant vitamins do not improve endothelial vasodilator function in postmenopausal women with established coronary artery disease: a substudy of the Women's Angiographic Vitamin and Estrogen (WAVE) trial.
- Author
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Kelemen M, Vaidya D, Waters DD, Howard BV, Cobb F, Younes N, Tripputti M, and Ouyang P
- Subjects
- Aged, Coronary Artery Disease physiopathology, Endothelium, Vascular drug effects, Endothelium, Vascular physiology, Estrogens administration & dosage, Estrogens, Conjugated (USP) administration & dosage, Female, Humans, Medroxyprogesterone Acetate administration & dosage, Middle Aged, Multivariate Analysis, Postmenopause, Treatment Failure, Vasodilation drug effects, Antioxidants administration & dosage, Ascorbic Acid administration & dosage, Coronary Artery Disease drug therapy, Estrogen Replacement Therapy, Vitamin E administration & dosage
- Abstract
We measured flow-mediated dilation (FMD) by high-resolution brachial ultrasound in 61 women who participated in the Women's Angiographic Vitamin and Estrogen (WAVE) trial, a randomized controlled trial. There were no significant differences in the baseline demographics of women receiving hormone therapy (0.625 mg/day of conjugated equine estrogen plus 2.5mg of medroxyprogesterone acetate for women who had not had a hysterectomy) or placebo; or vitamins (400 IU of Vitamin E and 500 mg of Vitamin C twice daily) or placebo. Baseline FMD was impaired in all subjects (3.3+/-7.6%). Neither hormone therapy (4.1+/-5.2% at baseline, 4.2+/-5.0% at 3 months, and 4.1+/-6.5% at 34 months) nor antioxidant vitamins (3.0+/-8.3% at baseline; 3.5+/-4.6% at 3 months; 3.1+/-7.6% at 34 months) improved FMD (all p-values=NS). Endothelium-independent vasodilation, induced by nitroglycerin (NTG) was similar at baseline and was not affected by either therapy. In univariate and multivariate analysis, neither hormone therapy nor antioxidant vitamins were associated with FMD. Women with established coronary artery disease have impaired flow-mediated vasodilation of the brachial artery that does not improve after 3 months or up to 34 months of treatment with postmenopausal hormone therapy or antioxidant vitamins.
- Published
- 2005
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46. The effects of hydroxy-methyl-glutaryl co-enzyme A reductase inhibitors on platelet thrombus formation.
- Author
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Thompson PD, Moyna NM, White CM, Weber KM, Giri S, and Waters DD
- Subjects
- Aged, Analysis of Variance, Blood Platelets physiology, Chi-Square Distribution, Coronary Artery Disease prevention & control, Coronary Thrombosis prevention & control, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Male, Middle Aged, Probability, Reference Values, Treatment Outcome, Blood Platelets drug effects, Coronary Artery Disease drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Pravastatin administration & dosage, Simvastatin administration & dosage
- Abstract
Background: Hydroxy-methyl-glutaryl co-enzyme A reductase inhibitors (HMG CoA RIs) markedly improve the lipid profile of patients with hypercholesterolemia, but the magnitude and time course of the effect of these drugs on other risk factors for atherosclerosis are not well defined., Methods: We employed a random assignment, double-blind design to compare the effect of 8 weeks of HMG CoA RI therapy with either pravastatin (40 mg QD; n=12) or simvastatin (20 mg QD; n=12) with placebo (n=13) on serum lipids, platelet thrombus formation (PTF), and markers of inflammation and thrombosis in patients with coronary artery disease. PTF was measured using a validated ex vivo perfusion chamber system., Results: Total and LDL cholesterol decreased 20.3 +/- 12.7% and 31.4 +/- 16.5% in the HMG CoA RI group and were unchanged with placebo (P<0.01). Triglycerides also decreased 15.3 +/- 22.5% with HMG CoA RI therapy, but increased 8.4 +/- 30.0% with placebo (P=0.01). PTF increased 54.1 +/- 89.0% with placebo and decreased 8.0 +/- 46.82% with HMG CoA RI treatment (P<0.01)., Conclusions: HMG CoA RI therapy with pravastatin or simvastatin reduces PTF after only 8 weeks of therapy. Such lipid effects may contribute to the prompt reduction in cardiovascular events noted in some clinical trials.
- Published
- 2002
- Full Text
- View/download PDF
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