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: In this paper, the relationship of systemic inflammatory disease, complement factor H (CFH ) Y402H (1277T→C) genotype status and age-related macular degeneration (AMD) prevalence in a multiethnic population of whites, blacks, Hispanics, and Chinese was described.
100 citations
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TL;DR: Auditory and nonauditory risk factors were identified, therefore suggesting that future directions aimed at assessing, preventing, and managing these types of HDs might benefit from information outside the traditional scope of audiology.
Abstract: OBJECTIVE Clinicians encounter patients who report experiencing hearing difficulty (HD) even when audiometric thresholds fall within normal limits. When there is no evidence of audiometric hearing loss, it generates debate over possible biomedical and psychosocial etiologies. It is possible that self-reported HDs relate to variables within and/or outside the scope of audiology. The purpose of this study is to identify how often, on a population basis, people with normal audiometric thresholds self-report HD and to identify factors associated with such HDs. DESIGN This was a cross-sectional investigation of participants in the Beaver Dam Offspring Study. HD was defined as a self-reported HD on a four-item scale despite having pure-tone audiometric thresholds within normal limits (<20 dB HL0.5, 1, 2, 3, 4, 6, 8 kHz bilaterally, at each frequency). Distortion product otoacoustic emissions and word-recognition performance in quiet and with competing messages were also analyzed. In addition to hearing assessments, relevant factors such as sociodemographic and lifestyle factors, environmental exposures, medical history, health-related quality of life, and symptoms of neurological disorders were also examined as possible risk factors. The Center for Epidemiological Studies-Depression was used to probe symptoms associated with depression, and the Medical Outcomes Study Short-Form 36 mental score was used to quantify psychological stress and social and role disability due to emotional problems. The Visual Function Questionnaire-25 and contrast sensitivity test were used to query vision difficulties. RESULTS Of the 2783 participants, 686 participants had normal audiometric thresholds. An additional grouping variable was created based on the available scores of HD (four self-report questions), which reduced the total dataset to n = 682 (age range, 21-67 years). The percentage of individuals with normal audiometric thresholds who self-reported HD was 12.0% (82 of 682). The prevalence in the entire cohort was therefore 2.9% (82 of 2783). Performance on audiological tests (distortion product otoacoustic emissions and word-recognition tests) did not differ between the group self-reporting HD and the group reporting no HD. A multivariable model controlling for age and sex identified the following risk factors for HD: lower incomes (odds ratio [OR] $50,000+ = 0.55, 95% confidence interval [CI] = 0.30-1.00), noise exposure through loud hobbies (OR = 1.48, 95% CI = 1.15-1.90), or firearms (OR = 2.07, 95% CI = 1.04-4.16). People reporting HD were more likely to have seen a doctor for hearing loss (OR = 12.93, 95% CI = 3.86-43.33) and report symptoms associated with depression (Center for Epidemiological Studies-Depression [OR = 2.39, 95% CI = 1.03-5.54]), vision difficulties (Visual Function Questionnaire-25 [OR = 0.93, 95% CI = 0.89-0.97]), and neuropathy (e.g., numbness, tingling, and loss of sensation [OR = 1.98, 95% CI = 1.14-3.44]). CONCLUSIONS The authors used a population approach to identify the prevalence and risk factors associated with self-reported HD among people who perform within normal limits on common clinical tests of auditory function. The percentage of individuals with normal audiometric thresholds who self-reported HD was 12.0%, resulting in an overall prevalence of 2.9%. Auditory and nonauditory risk factors were identified, therefore suggesting that future directions aimed at assessing, preventing, and managing these types of HDs might benefit from information outside the traditional scope of audiology.
100 citations
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TL;DR: The prevalence of macular telangiectasia type 2 (0.1%) is higher than previously thought and is useful in estimating the burden of this condition in the population.
99 citations
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TL;DR: Progression to proliferative retinopathy was related to higher LDL cholesterol, fibrinogen, serum triglycerides, albumin excretion rate, and glycosylated hemoglobin, whilst this was not the case in the presence of nephropathy.
Abstract: This study examined potential risk factors for the incidence and progression of retinopathy in a large representative cohort of childhood onset insulin-dependent diabetic patients. Participants in the Epidemiology of Diabetes Complications (EDC) Study underwent a full clinical examination at baseline and again at a 2-year follow-up. Retinopathy status was ascertained using stereo fundus photographs graded according to the modified Airlie House System. The study population is based on a large cohort of childhood-onset insulin-dependent diabetic patients, seen within 1 year of diagnosis at the Children's Hospital of Pittsburgh between January 1950 and May 1980. A total of 657 subjects participated at baseline (1986-1988), with 80% of eligible survivors taking part in the follow-up examination. This report concerns risk factors associated with the progression of diabetic retinopathy over a 2-year period, and the interaction of these factors with the presence of nephropathy. Analyses showed that baseline diastolic blood pressure was significantly associated with the incidence of any retinopathy, while glycosylated hemoglobin, baseline severity of retinopathy, serum triglycerides, and, to a lesser extent, higher levels of low-density lipoprotein (LDL) cholesterol and fibrinogen were associated with the progression of retinopathy. Progression to proliferative retinopathy was related to higher LDL cholesterol, fibrinogen, serum triglycerides, albumin excretion rate, and glycosylated hemoglobin (GHb). Risk factors varied with the presence of nephropathy. In the absence of nephropathy, GHb was a significant predictor of progression, whilst this was not the case in the presence of nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
99 citations
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TL;DR: In women in the authors' analyses, waist-to-hip ratio is more strongly associated with age-related eye disease than is body mass index, and when adiposity is considered as a risk factor itself, or as a confounder of risk factors for age- related ocular disease, waist tohip ratio may be the better measure to use in women.
Abstract: OBJECTIVE. To compare body mass index with waist-to-hip ratio as correlates of age-related eye disease. DESIGN. Population-based cross-sectional study. PARTICIPANTS. Participants of the Beaver Dam Eye Study at 5-year follow-up examinations. METHODS. Body mass index was computed from weight and height, and waist-to-hip ratio was computed from measurements all done at the 5-year examination. Presence of ocular lesions was based on gradings of standard photographs of the retina and lens. MAIN OUTCOME MEASURES. Presence of early and late age-related maculopathy and nuclear, cortical, and posterior subcapsular cataracts. RESULTS. In women, early age-related maculopathy was significantly associated with both body mass index and waist-to-hip ratio. The relationship between waist-to-hip ratio and late age-related maculopathy was of borderline significance. When analyzed as continuous measures, waist-to-hip ratio was more strongly associated with nearly every outcome compared to body mass index. In men, there was ...
98 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