J. David Spence

Bio: J. David Spence is an academic researcher from Robarts Research Institute. The author has contributed to research in topics: Stroke & B vitamins. The author has an hindex of 67, co-authored 399 publications receiving 17671 citations. Previous affiliations of J. David Spence include University of Western Ontario & New York University.

Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial.

Abstract: ContextIn observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk. However the utility of homocysteine-lowering therapy to reduce that risk has not been confirmed by randomized trials.ObjectiveTo determine whether high doses of folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins.DesignDouble-blind randomized controlled trial (September 1996–May 2003).Setting and Participants3680 adults with nondisabling cerebral infarction at 56 university-affiliated hospitals, community hospitals, private neurology practices, and Veterans Affairs medical centers across the United States, Canada, and Scotland.InterventionsAll participants received best medical and surgical care plus a daily multivitamin containing the US Food and Drug Administration's reference daily intakes of other vitamins; patients were randomly assigned to receive once-daily doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine, 0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation (n = 1853), containing 200 µg of pyridoxine, 6 µg of cobalamin,and 20 µg of folic acid.Main Outcome MeasuresRecurrent cerebral infarction (primary outcome); coronary heart disease (CHD) events and death (secondary outcomes).ResultsMean reduction of total homocysteine was 2 µmol/L greater in the high-dose group than in the low-dose group, but there was no treatment effect on any end point. The unadjusted risk ratio for any stroke, CHD event, or death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P = .80 by log-rank test of the primary hypothesis of difference in ischemic stroke between treatment groups). There was a persistent and graded association between baseline total homocysteine level and outcomes. A 3-µmol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P = .05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P = .001) in the low-dose group and a nonsignificantly lower risk in the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death.ConclusionsIn this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. However, the consistent findings of an association of total homocysteine with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary.

Atrial Fibrillation in Patients with Cryptogenic Stroke

Abstract: BACKGROUND Atrial fibrillation is a leading preventable cause of recurrent stroke for which early detection and treatment are critical. However, paroxysmal atrial fibrillation is often asymptomatic and likely to go undetected and untreated in the routine care of patients with ischemic stroke or transient ischemic attack (TIA). METHODS We randomly assigned 572 patients 55 years of age or older, without known atrial fibrillation, who had had a cryptogenic ischemic stroke or TIA within the previous 6 months (cause undetermined after standard tests, including 24-hour electrocardiography [ECG]), to undergo additional noninvasive ambulatory ECG monitoring with either a 30-day event-triggered recorder (intervention group) or a conventional 24-hour monitor (control group). The primary outcome was newly detected atrial fibrillation lasting 30 seconds or longer within 90 days after randomization. Secondary outcomes included episodes of atrial fibrillation lasting 2.5 minutes or longer and anticoagulation status at 90 days. RESULTS Atrial fibrillation lasting 30 seconds or longer was detected in 45 of 280 patients (16.1%) in the intervention group, as compared with 9 of 277 (3.2%) in the control group (absolute difference, 12.9 percentage points; 95% confidence interval [CI], 8.0 to 17.6; P<0.001; number needed to screen, 8). Atrial fibrillation lasting 2.5 minutes or longer was present in 28 of 284 patients (9.9%) in the intervention group, as compared with 7 of 277 (2.5%) in the control group (absolute difference, 7.4 percentage points; 95% CI, 3.4 to 11.3; P<0.001). By 90 days, oral anticoagulant therapy had been prescribed for more patients in the intervention group than in the control group (52 of 280 patients [18.6%] vs. 31 of 279 [11.1%]; absolute difference, 7.5 percentage points; 95% CI, 1.6 to 13.3; P = 0.01). CONCLUSIONS Among patients with a recent cryptogenic stroke or TIA who were 55 years of age or older, paroxysmal atrial fibrillation was common. Noninvasive ambulatory ECG monitoring for a target of 30 days significantly improved the detection of atrial fibrillation by a factor of more than five and nearly doubled the rate of anti coagulant treatment, as compared with the standard practice of short-duration ECG monitoring. (Funded by the Canadian Stroke Network and others; EMBRACE ClinicalTrials.gov number, NCT00846924.)

Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke

Abstract: BackgroundThe efficacy of closure of a patent foramen ovale (PFO) in the prevention of recurrent stroke after cryptogenic stroke is uncertain. We investigated the effect of PFO closure combined with antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new brain infarctions. MethodsIn this multinational trial involving patients with a PFO who had had a cryptogenic stroke, we randomly assigned patients, in a 2:1 ratio, to undergo PFO closure plus antiplatelet therapy (PFO closure group) or to receive antiplatelet therapy alone (antiplatelet-only group). Imaging of the brain was performed at the baseline screening and at 24 months. The coprimary end points were freedom from clinical evidence of ischemic stroke (reported here as the percentage of patients who had a recurrence of stroke) through at least 24 months after randomization and the 24-month incidence of new brain infarction, which was a composite of clinical ischemic stroke or silent brain infarction detected on...

Grapefruit juice–drug interactions

Abstract: The novel finding that grapefruit juice can markedly augment oral drug bioavailability was based on an unexpected observation from an interaction study between the dihydropyridine calcium channel antagonist, felodipine, and ethanol in which grapefruit juice was used to mask the taste of the ethanol. Subsequent investigations showed that grapefruit juice acted by reducing presystemic felodipine metabolism through selective post-translational down regulation of cytochrome P450 3A4 (CYP3A4) expression in the intestinal wall. Since the duration of effect of grapefruit juice can last 24 h, repeated juice consumption can result in a cumulative increase in felodipine AUC and Cmax. The high variability of the magnitude of effect among individuals appeared dependent upon inherent differences in enteric CYP3A4 protein expression such that individuals with highest baseline CYP3A4 had the highest proportional increase. At least 20 other drugs have been assessed for an interaction with grapefruit juice. Medications with innately low oral bioavailability because of substantial presystemic metabolism mediated by CYP3A4 appear affected by grapefruit juice. Clinically relevant interactions seem likely for most dihydropyridines, terfenadine, saquinavir, cyclosporin, midazolam, triazolam and verapamil and may also occur with lovastatin, cisapride and astemizole. The importance of the interaction appears to be influenced by individual patient susceptibility, type and amount of grapefruit juice and administration-related factors. Although in vitro findings support the flavonoid, naringin, or the furanocoumarin, 6',7'-dihydroxybergamottin, as being active ingredients, a recent investigation indicated that neither of these substances made a major contribution to grapefruit juice-drug interactions in humans.

Carotid Plaque Area A Tool for Targeting and Evaluating Vascular Preventive Therapy

Abstract: Background and Purpose—Carotid plaque area measured by ultrasound (cross-sectional area of longitudinal views of all plaques seen) was studied as a way of identifying patients at increased risk of stroke, myocardial infarction, and vascular death. Methods—Patients from an atherosclerosis prevention clinic were followed up annually for up to 5 years (mean, 2.51.3 years) with baseline and follow-up measurements recorded. Plaque area progression (or regression) was defined as an increase (or decrease) of 0.05 cm 2 from baseline. Results—Carotid plaque areas from 1686 patients were categorized into 4 quartile ranges: 0.00 to 0.11 cm 2 (n422), 0.12 to 0.45 cm 2 (n424), 0.46 to 1.18 cm 2 (n421), and 1.19 to 6.73 cm 2 (n419). The combined 5-year risk of stroke, myocardial infarction, and vascular death increased by quartile of plaque area: 5.6%, 10.7%, 13.9%, and 19.5%, respectively (P0.001) after adjustment for all baseline patient characteristics. A total of 1085 patients had 1 annual carotid plaque area measurements: 685 (63.1%) had carotid plaque progression, 306 (28.2%) had plaque regression, and 176 (16.2%) had no change in carotid plaque area over the period of follow-up. The 5-year adjusted risk of combined outcome was 9.4%, 7.6%, and 15.7% for patients with carotid plaque area regression, no change, and progression, respectively (P0.003). Conclusions—Carotid plaque area and progression of plaque identified high-risk patients. Plaque measurement may be useful for targeting preventive therapy and evaluating new treatments and response to therapy and may improve cost-effectiveness of secondary preventive treatment. (Stroke. 2002;33:2916-2922.)

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Standards of Medical Care in Diabetes

Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Abstract: Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...

Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association

Abstract: WRITING GROUP MEMBERS Emelia J. Benjamin, MD, SCM, FAHA Michael J. Blaha, MD, MPH Stephanie E. Chiuve, ScD Mary Cushman, MD, MSc, FAHA Sandeep R. Das, MD, MPH, FAHA Rajat Deo, MD, MTR Sarah D. de Ferranti, MD, MPH James Floyd, MD, MS Myriam Fornage, PhD, FAHA Cathleen Gillespie, MS Carmen R. Isasi, MD, PhD, FAHA Monik C. Jiménez, ScD, SM Lori Chaffin Jordan, MD, PhD Suzanne E. Judd, PhD Daniel Lackland, DrPH, FAHA Judith H. Lichtman, PhD, MPH, FAHA Lynda Lisabeth, PhD, MPH, FAHA Simin Liu, MD, ScD, FAHA Chris T. Longenecker, MD Rachel H. Mackey, PhD, MPH, FAHA Kunihiro Matsushita, MD, PhD, FAHA Dariush Mozaffarian, MD, DrPH, FAHA Michael E. Mussolino, PhD, FAHA Khurram Nasir, MD, MPH, FAHA Robert W. Neumar, MD, PhD, FAHA Latha Palaniappan, MD, MS, FAHA Dilip K. Pandey, MBBS, MS, PhD, FAHA Ravi R. Thiagarajan, MD, MPH Mathew J. Reeves, PhD Matthew Ritchey, PT, DPT, OCS, MPH Carlos J. Rodriguez, MD, MPH, FAHA Gregory A. Roth, MD, MPH Wayne D. Rosamond, PhD, FAHA Comilla Sasson, MD, PhD, FAHA Amytis Towfighi, MD Connie W. Tsao, MD, MPH Melanie B. Turner, MPH Salim S. Virani, MD, PhD, FAHA Jenifer H. Voeks, PhD Joshua Z. Willey, MD, MS John T. Wilkins, MD Jason HY. Wu, MSc, PhD, FAHA Heather M. Alger, PhD Sally S. Wong, PhD, RD, CDN, FAHA Paul Muntner, PhD, MHSc On behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics—2017 Update