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: The WESDR has provided precise estimates of the prevalence, and 4-year incidence and progression of diabetic retinopathy, and evidence of a possible causal relationship between specific risk factors, such as hyperglycemia and the development and progression in people with diabetes.
Abstract: The WESDR has provided precise estimates of the prevalence, and 4-year incidence and progression of diabetic retinopathy. It has provided evidence of a possible causal relationship between specific risk factors, such as hyperglycemia and the development and progression of retinopathy. Our data support current recommendations for ophthalmologic examinations for people with diabetes. In 1990 we will reexamine the cohort to determine the 10-year incidence and progression of diabetic retinopathy, macular edema, and visual impairment.
185 citations
01 Jan 1995
TL;DR: In this paper, the authors investigated the relationship of various retinal lesions to systemic hypertension in the population-based Beaver Dam Eye Study and found that retinopathy, arteriolar narrowing, and arteriovenous nicking are common in people with hypertension.
Abstract: Objective: To investigate the relationship of various retinal lesions to systemic hypertension in the population-based Beaver Dam Eye Study. Design: In this cross-sectional population-based study, blood pressure was measured using standardized protocols. Using standardized protocols, stereoscopic color fundus photographs were graded in a masked fashion to determine the presence of retinopathy (defined as retinal microaneurysms only, blot hemorrhages only, hemorrhages and/or microaneurysms, cotton-wool spots, hard exudates, intraretinal microvascular abnormalities, venous beading, and retinal new vessels), retinal arteriolar narrowing, and arteriovenous nicking. Participants: Subjects aged 43 through 84 years who lived in Beaver Dam, Wis, between 1987 and 1988 were examined between 1988 and 1990. People with diabetes or retinal vascular occlusions were excluded. Results: Retinopathy was present in 336 subjects (7.8%), arteriolar narrowing in 582 subjects (13.5%), and arteriovenous nicking in 95 subjects (2.2%) in the nondiabetic population. Hypertension was associated with increased frequency of retinopathy, arteriolar narrowing, and arteriovenous nicking. After adjusting for age, hypertension was associated with the presence of retinopathy (in men: relative risk [RR], 1.47; 95% confidence interval [CI], 1.10 to 1.96; in women: RR, 1.69; 95% CI, 1.26 to 2.27), arteriolar narrowing (in men: RR, 1.34; 95% CI, 1.03 to 1.74; in women: RR, 1.37; 95% CI, 1.14 to 1.64), and arteriovenous nicking (in men: RR, 1.87; 95% CI, 0.99 to 3.54; in women: RR, 1.65; 95% CI, 1.00 to 2.73). Retinopathy, arteriolar narrowing, and arteriovenous nicking were more frequent in those subjects whose blood pressure was elevated despite use of antihypertensive medications compared with those subjects whose blood pressure was controlled with antihypertensive medications or those who were normotensive. Conclusions: These data suggest that retinopathy and retinal arteriolar narrowing are common in people with hypertension. Further longitudinal study is necessary to evaluate the public health significance of these retinal lesions regarding possibly increased risk of renal and cardiovascular disease.
182 citations
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TL;DR: Data suggest that after controlling for age and sex, nuclear scleroticCataract severity, cataract surgery, and visual impairment are risk indicators for poorer survival.
Abstract: Objective: To investigate the relationship of cataract, age-related maculopathy, glaucoma, and visual impairment to survival in the population-based Beaver Dam Eye Study. Design: In this population-based study, visual acuity was measured with use of standardized protocols. At baseline, stereoscopic color fundus photographs and color slit-lamp and retroillumination photographs were graded in a masked fashion to determine the presence of age-related maculopathy and cataract, respectively. Deaths were ascertained by contacting family members, daily review of obituaries, and use of vital status records. Participants: Subjects aged 43 through 84 years who lived in Beaver Dam, Wis, were identified and examined between 1988 and 1990. Results: From the time of the baseline examination until a median of 4 years later, 9.5% (467/4926) of the population had died. After correcting for age and sex, poorer survival was associated with more severe nuclear sclerosis (5-year survival of 88.9% for the most severe compared with 94.1% for the least severe stage) and visual impairment (5-year survival of 87.5% for impaired compared with 91.8% for unimpaired vision). However, after controlling for systemic factors, only more severe nuclear sclerosis in people without diabetes was significantly associated with poorer survival (hazard ratio per level of severity, 1.19; 95% confidence interval, 1.00 to 1.40). Conclusions: These data suggest that after controlling for age and sex, nuclear sclerotic cataract severity, cataract surgery, and visual impairment are risk indicators for poorer survival. Cortical cataract, posterior subcapsular cataract, glaucoma, and age-related maculopathy were unrelated to poorer survival.
180 citations
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TL;DR: Since 1985, diabetic patients have lower rates of progression to PDR and SVL, which may reflect an increased awareness of retinopathy risk factors; earlier identification and initiation of care for patients withretinopathy; and improved medical management of glucose, blood pressure, and serum lipids.
Abstract: OBJECTIVE This meta-analysis reviews rates of progression of diabetic retinopathy to proliferative diabetic retinopathy (PDR) and/or severe visual loss (SVL) and temporal trends. RESEARCH DESIGN AND METHODS This systematic literature review and meta-analysis of prospective studies assesses progression of retinopathy among diabetic patients without treatment for retinopathy at baseline. Studies published between 1975 to February 2008 were identified. Outcomes of interest were rates of progression to PDR and/or SVL. Pooled baseline characteristics and outcome measures were summarized using weighted averages of counts and means. Baseline characteristics and outcomes were compared between two periods: 1975–1985 and 1986–2008. RESULTS A total of 28 studies comprising 27,120 diabetic patients (mean age 49.8 years) were included. After 4 years, pooled incidence rates for PDR and SVL were 11.0 and 7.2%, respectively. Rates were lower among participants in 1986–2008 than in 1975–1985. After 10 years, similar patterns were observed. Participants in 1986–2008 studies had lower proportions of PDR and non-PDR at all time points than participants in 1975–1985 studies. CONCLUSIONS Since 1985, diabetic patients have lower rates of progression to PDR and SVL. These findings may reflect an increased awareness of retinopathy risk factors; earlier identification and initiation of care for patients with retinopathy; and improved medical management of glucose, blood pressure, and serum lipids. Differences in baseline characteristics, particularly in the prevalence and severity of retinopathy, could also have contributed to these temporal differences.
180 citations
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TL;DR: There are several risk factors for LEA with potential for modification and preventive strategies, and the cumulative 14-year incidence of LEA was 7.2% in younger- and 9.9% in older-onset patients.
Abstract: OBJECTIVE: To estimate the cumulative 14-year incidence of lower-extremity amputations (LEAs) and evaluate risk factors for LEA. RESEARCH DESIGN AND METHODS: Study subjects consisted of population-based cohorts of younger-onset (diagnosed before age 30 years and taking insulin, n = 906) and older-onset (diagnosed after age 30 years, n = 984) individuals with diabetes. Subjects participated in baseline (1980-1982), 4-year, 10-year, and 14-year examinations or interviews. LEAs were determined by history. RESULTS: The cumulative 14-year incidence of LEA was 7.2% in younger- and 9.9% in older-onset patients. In multivariable analyses based on the discrete linear logistic model, LEA in the younger-onset group was more likely for males (odds ratio [OR] 5.21 [95% CI 2.50-10.88]), older age (OR for 10 years 1.71 [1.30-2.24]), higher glycosylated hemoglobin (OR for 1% 1.39 [1.22-1.59]), higher diastolic blood pressure (OR for 10 mmHg 1.58 [1.20-2.07]), history of ulcers of the feet (3.19 [1.71-5.95]), and more severe retinopathy (OR for one step 1.16 [1.08-1.24]). In younger-onset patients aged > or = 18, pack-years smoked (OR for 10 years 1.20 [1.03-1.41]) was also associated with LEAs, and daily aspirin use was inversely associated (OR 0.11 [0.01-0.83]). In the older-onset group, LEA was more likely for men (2.66 [1.49, 4.76]) and if the subject had higher glycosylated hemoglobin (OR for 1% 1.25 [1.09-1.43]), higher pulse pressure (OR for 10 mmHg 1.19 [1.04-1.37]), history of ulcers (3.56 [1.84-6.89]), and more severe retinopathy (OR for one step 1.07 [1.00-1.13]). CONCLUSIONS: There are several risk factors for LEA with potential for modification and preventive strategies.
178 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