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
Papers
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TL;DR: Findings support evidence for common pathways influencing ocular and renal function and suggest that further work is required on their common determinants.
Abstract: In this study, we investigated the associations of complement factor H (CFH) and hemicentin-1 (HMCN1) with age-related macular degeneration (AMD) and renal function. Three scales, measuring the course of AMD and drusen development, were examined in two samples: the Family Age-Related Macular degeneration Study (FARMS), consisting of families ascertained through a single individual with severe AMD, and an unascertained population-based family cohort, the Beaver Dam Eye Study (BDES), which was also used to assess longitudinal changes in AMD and associations with renal function. Associations were performed by a regression accounting for known risk factors as well as familial and sibling effects. Strong evidence of the association of rs1061170 (Y402H) variation with AMD was confirmed (P 5 9.15 3 10 25 in BDES, P 5 0.016 in FARMS). This association was observed in multiple AMD scales, suggesting that its role is not phenotypespecific. Polymorphisms in both CFH and HMCN1 appeared to influence the longitudinal rate of change of AMD. The rs1061170 polymorphism was also associated with a reduction in estimated glomerular filtration rate (eGFR) (P 5 0.046). Another CFH polymorphism, rs800292, was similarly associated with eGFR [b 52 0.90 (P 5 0.022)]. Associations between rs743137 (P 5 0.05) and rs680638 (P 5 0.022) in HMCN1 with calculated creatinine clearance progression were also observed. Both genes appear to play a role in both AMD and renal pathophysiology. These findings support evidence for common pathways influencing ocular and renal function and suggest that further work is required on their common determinants.
54 citations
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TL;DR: Recommendations include intensive training of primary-care physicians in ophthalmoscopy, use of objective recording of retinopathy by fundus photography with interpretation of fundus photographs by retinal specialists, and better communication between primary-Care physicians and retinal specialist.
Abstract: Diabetic retinopathy is a leading cause of blindness in the United States. Photocoagulation has been shown to reduce visual loss from macular edema and proliferative retinopathy. Because serious diabetic retinopathy may be asymptomatic and its detection difficult, several recommendations have been made by the National Diabetes Advisory Board for routine ophthalmologic examinations to ensure timely treatment. In geographic areas devoid of ophthalmologists, alternate approaches are necessary. These include intensive training of primary-care physicians in ophthalmoscopy, use of objective recording of retinopathy by fundus photography with interpretation of fundus photographs by retinal specialists, and better communication between primary-care physicians and retinal specialists.
54 citations
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TL;DR: Three modifiable behaviors-smoking, drinking alcohol, and physical activity-were associated with changes in vision and incidence of visual impairment over a 20-year period.
53 citations
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TL;DR: There is a relationship between the level of serum cystatin C and chronic kidney disease with the incidence of AMD and the underlying biological processes remain to be determined.
Abstract: Objective To examine the associations of the serum cystatin C level and chronic kidney disease with the incidence of age-related macular degeneration (AMD) over 15 years. Methods In this population-based cohort study of 4926 individuals aged 43 to 86 years at baseline, 3779 participated in 1 or more follow-up examinations. Age-related macular degeneration was determined by grading photographs of the macula. Individuals were defined as having mild or moderate to severe chronic kidney disease based on a value of more than 45 mL/min/1.73 m 2 to 60 mL/min/1.73 m 2 or less and 45 mL/min/1.73 m 2 or less, respectively, according to the Modification of Diet in Renal Disease Study equation. Results While controlling for age and other risk factors, the level of serum cystatin C at baseline was associated with the incidence of early AMD (odds ratio per log standard deviation [95% confidence interval], 1.16 [1.01-1.35]) and exudative AMD (1.42 [1.03-1.96]) but not geographic atrophy (0.89 [0.56-1.41]) or progression of AMD (1.02 [0.88-1.18]). Mild chronic kidney disease was associated with the 15-year cumulative incidence of early AMD (odds ratio per log standard deviation, 1.36 [95% confidence interval, 1.00-1.86]) but not the incidence of other AMD end points. Conclusion There is a relationship between the level of serum cystatin C and chronic kidney disease with the incidence of AMD. The underlying biological processes remain to be determined.
53 citations
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TL;DR: Population-based data on the frequency and incidence of retinopathy from the time of diagnosis of insulin-dependent diabetes mellitus provided by this study suggest a possible reduction in risk of developingretinopathy in those in whom glycemic control is achieved from thetime of diagnosis.
Abstract: Objective: To describe the prevalence at baseline and 4-year incidence of retinopathy and its relation to glycemic control from the time of diagnosis of insulin-dependent diabetes. Design: Geographically defined population-based study. Setting: Twenty-eight-county area in Wisconsin. Study Population: Incipient cohort of children, teenagers, and young adults (n=354) up to 30 years of age with newly diagnosed insulin-dependent diabetes. Main Outcome Measure: Diabetic retinopathy as determined by gradings from 30° color stereoscopic photographs of the Diabetic Retinopathy Study 7 standard fields. Results: The prevalence of retinopathy at diagnosis was 1.3%. Four years after diagnosis of diabetes, retinopathy was first identified in 5.1% of our cohort and in 9.7% of those 15 years of age or older. After controlling for age, subjects with a mean glycosylated hemoglobin level of 12% or greater were 3.2 times as likely (95% confidence interval, 1.1-9.9) to have retinopathy present at follow-up as were subjects with a mean glycosylated hemoglobin level of less than 12%. Conclusion: Population-based data on the frequency and incidence of retinopathy from the time of diagnosis of insulin-dependent diabetes mellitus provided by this study suggest a possible reduction in risk of developing retinopathy in those in whom glycemic control is achieved from the time of diagnosis.
53 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