Author
Ronald Klein
Other affiliations: Los Angeles Biomedical Research Institute, Wake Forest University, LSU Health Sciences Center Shreveport ...read more
Bio: Ronald Klein is an academic researcher from University of Wisconsin-Madison. The author has contributed to research in topics: Population & Diabetic retinopathy. The author has an hindex of 194, co-authored 1305 publications receiving 149140 citations. Previous affiliations of Ronald Klein include Los Angeles Biomedical Research Institute & Wake Forest University.
Papers published on a yearly basis
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TL;DR: In this article, the authors describe the 15-year incidence of retinal vein occlusion and associated risk factors, including age, history of barbiturate use, serum creatinine level, and serum ionized calcium level.
Abstract: Objectives To describe the 15-year incidence of retinal vein occlusion (central retinal vein occlusion and branch retinal vein occlusion) and associated risk factors. Methods A population-based study where branch retinal vein occlusion and central retinal vein occlusion were detected at baseline (n = 4068, 1988-1990) and three 5-year follow-up examinations by grading 30° color fundus photographs. Results The 15-year cumulative incidences of branch retinal vein occlusion and central retinal vein occlusion were 1.8% and 0.5%, respectively. Using a generalized estimating equation model, incident retinal vein occlusion was related to baseline age (odds ratio [OR] per 10 years, 1.70; 95% confidence interval [CI], 1.36-2.12), history of barbiturate use (OR, 5.30; 95% CI, 2.28-12.31), focal retinal arteriolar narrowing (OR, 2.45; 95% CI, 1.29-4.66), glaucoma (OR, 3.17; 95% CI, 1.50-6.69), serum ionized calcium level (OR per 0.4 mg/dL, 0.43; 95% CI, 0.23-0.79), serum phosphorus level (OR per 0.3 mg/dL, 1.15; 95% CI, 1.01-1.30), and serum creatinine level (OR for ≥ 1.4 vs Conclusions Incident retinal vein occlusion is not infrequent in the population, especially after age 65 years. The relationships of barbiturate use, serum creatinine level, serum ionized calcium level, and serum phosphorus level with incident retinal vein occlusion require further assessment in other large population-based studies.
341 citations
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TL;DR: Serum total and high-density lipoprotein (HDL) cholesterol were measured in a sample of individuals examined between 1984 and 1986 and support the current management strategies for diabetes, which include control of level of glycemia, blood pressure, and blood lipids.
336 citations
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TL;DR: Several factors offer potential for modification for the prevention of amputations but require further study, including blood pressure, glycosylated hemoglobin, and smoking.
Abstract: Objective.—— To describe the incidence of lower extremity amputations and sores or ulcers and investigate risk factors for these complications. Design.— Cohort. Setting.— Primary care. Participants.— Population-based sample (N =1210) of younger-onset diabetic persons (diagnosed before age 30 years and taking insulin) and a stratified random sample (N =1780) of older-onset diabetic persons (diagnosed after age 30 years). Baseline and 4-year follow-up examinations were completed by 996 and 891 younger-onset persons, respectively, and by 1370 and 987 older-onset persons, respectively. Main Outcome Measures.—— Amputations and sores or ulcers of the lower extremities. Results. — Four-year incidence of amputations was 2.2% in both groups. Incidence of sores or ulcers was 9.5% in younger-onset and 10.5% in older-onset persons. In younger-onset persons, significant risk factors for amputation with odds ratios (and 95% confidence intervals) include age, 2.0 for 10 years (1.2 to 3.1), history of sores or ulcers, 10.5 (3.7 to 29.8), diastolic blood pressure, 2.1 for 10 mm Hg (1.3 to 3.5), and pack-years smoked, 1.3 for 10 years (1.0 to 1.6). Risk factors for sores or ulcers include glycosylated hemoglobin, 1.6 for 2% (1.3 to 2.0), retinopathy, 1.3 for two steps (1.1 to 1.6), and current smoking, 2.3 (1.0 to 5.6). In older-onset persons, risk factors for amputation are history of sores or ulcers, 4.6 (1.7 to 12.2), proteinuria, 4.3 (1.6 to 11.5), glycosylated hemoglobin, 1.5 for 2% (1.0 to 2.2), sex, 2.8 for males (1.0 to 7.5), and duration of diabetes, 1.8 for 10 years (1.0 to 3.2). For sores or ulcers, risk factors are glycosylated hemoglobin, 1.6 for 2% (1.3 to 2.0), duration, 1.5 for 10 years (1.0 to 2.1), proteinuria, 2.2 (1.1 to 4.3), and diastolic blood pressure, 0.8 for 10 mm Hg (0.6 to 1.0). Conclusions.— Several factors offer potential for modification for the prevention of amputations but require further study. These include blood pressure, glycosylated hemoglobin, and smoking. (Arch Intern Med. 1992;152:610-616)
335 citations
01 Jan 2016
TL;DR: Investigation of retinal vein occlusion is not infrequent in the population, especially after age 65 years, and the relationships of barbiturate use, serum creatinine level, serum ionized calcium level, and serum phosphorus level with incident Retinal vein Occlusion require further assessment in other large population-based studies.
Abstract: Results: The 15-year cumulative incidences of branch retinal vein occlusion and central retinal vein occlusion were 1.8% and 0.5%, respectively. Using a generalized estimating equation model, incident retinal vein occlusion was related to baseline age (odds ratio [OR] per 10 years,1.70;95%confidenceinterval[CI],1.36-2.12),history of barbiturate use (OR, 5.30; 95% CI, 2.28-12.31), focalretinalarteriolarnarrowing(OR,2.45;95%CI,1.294.66), glaucoma (OR, 3.17; 95% CI, 1.50-6.69), serum ionized calcium level (OR per 0.4 mg/dL, 0.43; 95% CI, 0.23-0.79), serum phosphorus level (OR per 0.3 mg/dL, 1.15;95%CI,1.01-1.30),andserumcreatininelevel(OR for 1.4 vs1.4 mg/dL, 1.61; 95% CI, 1.00-2.59). Migraine headache history was associated with branch retinal vein occlusion (OR, 1.99; 95% CI, 1.08-3.67). Diabetes history was associated with central retinal vein occlusion (OR, 6.35; 95% CI, 1.90-21.27). Conclusions: Incident retinal vein occlusion is not infrequent in the population, especially after age 65 years. Therelationshipsofbarbiturateuse,serumcreatininelevel, serumionizedcalciumlevel,andserumphosphoruslevel with incident retinal vein occlusion require further assessment in other large population-based studies.
324 citations
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TL;DR: Whether retinal arteriolar narrowing is related to incident hypertension in a cohort of middle-aged normotensive persons is examined and the value of specific antihypertensive treatment targeted at the peripheral microcirculation remains questionable.
Abstract: Researchers have speculated that narrowing of the small arterioles contributes to the pathogenesis of hypertension. In this prospective study, patients who were normotensive at baseline but had nar...
322 citations
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TL;DR: Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
Abstract: Background Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. Methods A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. Results In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. Conclusions Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
21,148 citations
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TL;DR: The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use.
Abstract: The Modification of Diet in Renal Disease (MDRD) Study equation underestimates glomerular filtration rate (GFR) in patients with mild kidney disease. Levey and associates therefore developed and va...
18,691 citations
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TL;DR: In those older than age 50, systolic blood pressure of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP, and hypertension will be controlled only if patients are motivated to stay on their treatment plan.
Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.
14,975 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: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
12,661 citations