Author
John J.P. Kastelein
Bio: John J.P. Kastelein is an academic researcher from University of Amsterdam. The author has contributed to research in topics: Familial hypercholesterolemia & Cholesterol. The author has an hindex of 138, co-authored 802 publications receiving 87937 citations.
Papers published on a yearly basis
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Brigham and Women's Hospital1, Novartis2, Baylor College of Medicine3, Federal University of São Paulo4, Technische Universität München5, University of Amsterdam6, St. John's University7, University of Pavol Jozef Šafárik8, McGill University9, First Faculty of Medicine, Charles University in Prague10, University of Szeged11, Iuliu Hațieganu University of Medicine and Pharmacy12, University of East Anglia13, Tohoku University14, Sahlgrenska University Hospital15
TL;DR: Antiinflammatory therapy targeting the interleukin‐1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid‐level lowering.
Abstract: BackgroundExperimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. MethodsWe conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. ResultsAt 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in t...
5,660 citations
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TL;DR: It is shown that statin therapy reduces high-sensitivity C-reactive protein levels as well as cholesterol, but no prospective trials have directly addressed the issue of whether elevated levels of high-magnifying C- reactive protein are beneficial for apparently healthy people.
Abstract: Previous studies have shown that statin therapy reduces high-sensitivity C-reactive protein levels as well as cholesterol, but no prospective trials have directly addressed the issue of whether elevated levels of high-sensitivity C-reactive protein are beneficial for apparently healthy perso
3,762 citations
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Tanya M. Teslovich1, Kiran Musunuru, Albert V. Smith2, Andrew C. Edmondson3 +215 more•Institutions (46)
TL;DR: The results identify several novel loci associated with plasma lipids that are also associated with CAD and provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
Abstract: Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
3,469 citations
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TL;DR: Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of least-in- LDL cholesterol levels per day, with a greater incidence of elevated aminotransferase levels.
Abstract: background Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD). methods A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non–procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. results The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality. conclusions Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.
3,141 citations
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The Heart Research Institute1, St Bartholomew's Hospital2, Karolinska Institutet3, University of Amsterdam4, Pierre-and-Marie-Curie University5, Autonomous University of Madrid6, Columbia University7, Université de Montréal8, University of California, San Francisco9, Pfizer10, University of Wisconsin-Madison11
TL;DR: Although there was evidence of an off-target effect of torcetrapib, it cannot rule out adverse effects related to CETP inhibition, and the trial was terminated prematurely because of an increased risk of death and cardiac events.
Abstract: Background Inhibition of cholesteryl ester transfer protein (CETP) has been shown to have a substantial effect on plasma lipoprotein levels. We investigated whether torcetrapib, a potent CETP inhibitor, might reduce major cardiovascular events. The trial was terminated prematurely because of an increased risk of death and cardiac events in patients receiving torcetrapib. Methods We conducted a randomized, double-blind study involving 15,067 patients at high cardiovascular risk. The patients received either torcetrapib plus atorvastatin or atorvastatin alone. The primary outcome was the time to the first major cardiovascular event, which was defined as death from coronary heart disease, nonfatal myocardial infarction, stroke, or hospitalization for unstable angina. Results At 12 months in patients who received torcetrapib, there was an increase of 72.1% in high-density lipoprotein cholesterol and a decrease of 24.9% in low-density lipoprotein cholesterol, as compared with baseline (P<0.001 for both compari...
2,832 citations
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TL;DR: In this article, a randomized controlled trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly people was presented. But the authors did not discuss the effect of the combination therapy in patients living with systolic hypertension.
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 …
14,173 citations
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TL;DR: In this article, Anderson et al. proposed a new FAHA Chair, Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect, Alice K. Jacobs et al., this article and Biykem Bozkurt.
11,386 citations
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Theo Vos1, Amanuel Alemu Abajobir, Kalkidan Hassen Abate2, Cristiana Abbafati3 +775 more•Institutions (305)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
10,401 citations
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TL;DR: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the management of Arterspertension of the European Society ofhypertension (ESH) and of theEuropean 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).
9,932 citations
01 Jan 2014
TL;DR: 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.
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.
9,618 citations