Ronald Klein

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.

Admixture Mapping Scans Identify a Locus Affecting Retinal Vascular Caliber in Hypertensive African Americans: the Atherosclerosis Risk in Communities (ARIC) Study

Abstract: Retinal vascular caliber provides information about the structure and health of the microvascular system and is associated with cardiovascular and cerebrovascular diseases. Compared to European Americans, African Americans tend to have wider retinal arteriolar and venular caliber, even after controlling for cardiovascular risk factors. This has suggested the hypothesis that differences in genetic background may contribute to racial/ethnic differences in retinal vascular caliber. Using 1,365 ancestry-informative SNPs, we estimated the percentage of African ancestry (PAA) and conducted genome-wide admixture mapping scans in 1,737 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) representing summary measures of retinal arteriolar and venular caliber, respectively, were measured from retinal photographs. PAA was significantly correlated with CRVE (r=0.071, P=0.003), but not CRAE (r=0.032, P=0.182). Using admixture mapping, we did not detect significant admixture association with either CRAE (genome-wide score= 20.73) or CRVE (genome-wide score= 20.69). An a priori subgroup analysis among hypertensive individuals detected a genome-wide significant association of CRVE with greater African ancestry at chromosome 6p21.1 (genome-wide score=2.31, locus-specific LOD=5.47). Each additional copy of an African ancestral allele at the 6p21.1 peak was associated with an average increase in CRVE of 6.14 mm in the hypertensives, but had no significant effects in the non-hypertensives (P for heterogeneity ,0.001). Further mapping in the 6p21.1 region may uncover novel genetic variants affecting retinal vascular caliber and further insights into the interaction between genetic effects of the microvascular system and hypertension.

The Prevalence of Age-related Maculopathy by Geographic Region and Ethnicity. The Colorado-Wisconsin Study of Age-Related Maculopathy

Abstract: Objectives: To determine the prevalence of age-related maculopathy (ARM) in a biethnic population and to determine if there are ethnic and/or geographic differences in the prevalence of ARM. Design: Prevalence data from 2 population-based studies, the San Luis Valley Diabetes Study (n=1541, ages 21-74 years) and the Beaver Dam Eye Study (n=3999, ages 43-74 years), were compared. Setting: Southern Colorado and central Wisconsin. Main Outcome Measure: Color stereoscopic fundus photographs were graded for ARM using the Wisconsin Age-related Maculopathy Grading System. Similar questionnaire, laboratory, and clinical data on potential risk factors were available from both studies. Results: Late-stage ARM was significantly less frequent among Hispanics than non-Hispanic whites (NHW) in Beaver Dam (odds ratio [OR]=0.07; 95% confidence interval [CI] =0.01-0.49; Hispanics vs Beaver Dam NHW). The prevalence of any ARM was significantly lower among San Luis Valley NHW (10.4%) than Beaver Dam NHW (14.3%) (OR=0.67; 95% CI=0.50-0.91). This prevalence difference was not explained by any of the risk factors examined (smoking, cardiovascular disease, diabetes, alcohol consumption, etc). The 2 NHW groups reported different European heritages. Conclusions: Late-stage ARM appeared to be rare among Hispanics but there was no ethnic difference in prevalence of any ARM. The 33% difference in risk among NHW by geographic location was not reduced when controlling for possible risk factors or confounders, suggesting that genetic heritage may be an important determinant of risk for ARM.

Effect of Doxycycline vs Placebo on Retinal Function and Diabetic Retinopathy Progression in Mild to Moderate Nonproliferative Diabetic Retinopathy: A Randomized Proof-of-Concept Clinical Trial

Abstract: Importance Microglia have been associated with inflammatory changes underlying diabetic retinopathy. Objective To investigate whether low-dose oral doxycycline monohydrate, a drug capable of inhibiting microglial activation, can improve or slow the deterioration of retinal function and whether it can induce regression or slow progression of diabetic retinopathy in patients with mild to moderate nonproliferative diabetic retinopathy (NPDR). Design, Setting, and Participants Randomized, double-masked, 24-month proof-of-concept clinical trial. We randomized 33 patients (from the Penn State Hershey Eye Center) with at least 1 eye with mild to moderate NPDR (Early Treatment Diabetic Retinopathy Study level 20-43) to doxycycline monohydrate, 50 mg/d, or daily placebo for 24 months. Main Outcomes and Measures Mean change at 24 months compared with baseline in the foveal sensitivity of matrix frequency-doubling perimetry in each treatment group. We also compared the 2 groups with respect to change from baseline to 24 months in functional variables (Humphrey photopic visual field testing using the Swedish interactive thresholding algorithm 24-2 strategy, contrast sensitivity, dark adaptation, visual acuity, and quality of life) and anatomical variables (diabetic retinopathy severity level, area of retinal thickening, central subfield thickness on optical coherence tomography, and macular volume on optical coherence tomography). Results From baseline to month 24, no significant difference was detected between groups with respect to all visual function and anatomical outcomes assessed. Conclusions and Relevance Although a link between low-dose oral anti-inflammatory agents and subclinical improvement in inner retinal function has been suggested in patients with severe NPDR or non–high-risk proliferative diabetic retinopathy, the same association was not found in the present study of patients with mild to moderate NPDR. The different findings in the 2 patient populations may relate to a differential effect of doxycycline on different stages of diabetic retinal dysfunction, or the sample size of the present study may be too small to detect a treatment effect of doxycycline in patients with mild to moderate NPDR. Trial Registration clinicaltrials.gov Identifier:NCT00917553

Barriers to prevention of vision loss caused by diabetic retinopathy.

Abstract: ARCHIVES OF FAMILY MEDICINE Primary Care Physicians' Practice Patterns and Diabetic Retinopathy: Current Levels of Care Stephanie Kakos Kraft, MPH; David G. Marrero, PhD; Emmanuel N. Lazaridis, PhD; Naomi Fineberg, PhD; Chunfu Qiu, PhD; Charles M. Clark, Jr, MD Background: Diabetic retinopathy is a costly and prevalent complication of diabetes mellitus. Objective: To assess primary care physicians' self-reported practice patterns for the screening and detection of diabetic retinopathy relative to published guidelines. Participants and Methods: All primary care physicians (defined as general internists, family practitioners, and general practitioners) in Indiana were identified and surveyed using a mailed questionnaire. Of 2390 physicians, 1508 (63%) responded and were determined to be eligible. Of these 1508 physicians, 1058 (70%) completed all or some of the eye care-related questions. For each eye care practice, physicians were asked to specify the proportion of patients to which the practice was applied and the frequency (eg, every

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.

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.

A New Equation to Estimate Glomerular Filtration Rate

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...

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

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.

2013 ESH/ESC 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).

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 …

A global reference for human genetic variation.

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.