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.

Severe Hypoglycemia and Smoking in a Long-Term Type 1 Diabetic Population: Wisconsin Epidemiologic Study of Diabetic Retinopathy

Abstract: Objective To evaluate the relationship of severe hypoglycemia (SH) and smoking in a population-based cohort of persons with long-term type 1 diabetes. Research Design and Methods Cross-sectional analysis of the population-based cohort of the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). The analyses in this report were limited to 537 type 1 diabetes individuals with complete data who participated in the last examination phase (2000-2001). SH was defined as having one or more episodes of loss of consciousness or overnight hospitalization due to hypoglycemia in a one year period prior to the examination. Results The prevalence of SH in this population was 14.3%. In univariate analysis, current smokers had a greater chance of having SH compared to never smokers: OR and 95% CI 2.40 (1.30-4.40). When controlling for relevant confounders such as age, gender, glycosylated hemoglobin, waist-hip ratio, orthostatic hypotension, alcohol consumption, intensive insulin treatment, past history of severe hypoglycemia, and late complications of diabetes (nephropathy, neuropathy, and retinopathy), the association remained statistically significant with current smoking presenting approximately 2.6 times greater odds of developing SH. Conclusions Current smokers with type 1 diabetes have higher odds of SH episodes.

Is age-related Maculopathy related to hearing loss?

Abstract: Objective To describe the relationship of age-related maculopathy (ARM) to hearing loss. Design Population-based cohort study. Participants All 3397 adults (age range, 48-92 years) living in Beaver Dam, Wis, who were examined for age-related eye disease and hearing loss from March 1, 1993, to July 18, 1995, and who had analyzable hearing thresholds in at least 1 ear and fundus photographs gradable for ARM in at least 1 eye. Methods Characteristics of drusen and other lesions typical of ARM were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. We used standard protocols of pure-tone air-conduction audiometry to assess hearing loss, which was defined as the pure-tone average of hearing thresholds at 500, 1000, 2000, and 4000 Hz greater than 25-dB hearing level. Results The prevalence of ARM was 25.4% and of hearing loss was 45.0% in this population. Both conditions were present in 15.1%. The relationships between early ARM lesions and hearing loss were not statistically significant. After controlling for age and sex, persons with late ARM were more likely (odds ratio, 3.15; 95% confidence interval, 1.34-7.42) to have hearing loss than persons without late ARM. This relation did not change when other factors related to ARM or hearing loss (eg, cigarette smoking status, history of occupational noise exposure, and history of cardiovascular disease) were entered into multivariate models. Conclusions These population-based estimates document the frequent coexistence of signs of ARM and hearing loss. As late ARM is an important cause of loss of vision, and as hearing loss is associated with difficulty in communicating, the high frequencies of sensory comorbidity may affect maintenance of independent functioning as people age. Further study is necessary to examine why late ARM and hearing loss are associated.

Severity of age-related macular degeneration in 1 eye and the incidence and progression of age-related macular degeneration in the fellow eye: the Beaver Dam Eye Study.

Abstract: Importance Previous studies regarding the severity of age-related macular degeneration (AMD) in 1 eye and its prognostic implications for the fellow eye have focused on the incidence of neovascular AMD in the fellow eye of participants with neovascular AMD in the other eye. It is unclear to what extent the severity of AMD in 1 eye affects the incidence, progression, and regression of AMD in its fellow eye across the entire range of AMD severity. Objective To investigate the effect of the severity of AMD in 1 eye on the incidence, progression, and regression of AMD in the fellow eye. Design, Setting and Participants The Beaver Dam Eye Study is a longitudinal population-based study of age-related eye diseases conducted in the city and township of Beaver Dam, Wisconsin. Examinations were performed every 5 years over a 20-year period (from the baseline examination in 1988-1990 to 2008-2010). Study participants (n = 4379) were 43 to 86 years of age at the baseline examination. At baseline and in up to 4 subsequent examinations, retinal photographs were taken. Main Outcomes and Measures Incidence, progression, and regression of AMD (assessed by use of the Wisconsin Age-Related Maculopathy Grading System on retinal photographs and adjusted for age, sex, and the Y402H polymorphism in the complement factor H gene on chromosome 1q) and mortality. Results More severe AMD in 1 eye was associated with increased incidence of AMD and accelerated progression in its fellow eye (levels 1-2: hazard ratio [HR], 4.90 [95% CI, 4.26-5.63]; levels 2-3: HR, 2.09 [95% CI, 1.42-3.06]; levels 3-4: HR, 2.38 [95% CI, 1.74-3.25]; levels 4-5: HR, 2.46 [95% CI, 1.65-3.66]). Less severe AMD in 1 eye was associated with less progression of AMD in its fellow eye (levels 2-3: HR, 0.42 [95% CI, 0.33-0.55]; levels 3-4: HR, 0.50 [95% CI, 0.34-0.83]). We estimate that 51% of participants who develop any AMD always maintain AMD severity states within 1 step of each other between eyes; 90% of participants stay within 2 steps. Conclusions and Relevance Using multistate models, we show that AMD severity in 1 eye tracks AMD severity in its fellow eye.

Relation of ocular trauma to cortical, nuclear, and posterior subcapsular cataracts: the Beaver Dam Eye Study

Abstract: Background: The consequences of minor ocular trauma in the general population are unclear. The relation of self reported ocular trauma to cortical, nuclear, and posterior subcapsular cataracts is described in a defined population. Methods: Population based, cross sectional study involving all people aged 43 to 86 years, living in Beaver Dam, Wisconsin (n=4926). Ocular trauma was ascertained by interview and cataract was graded from lens photographs. The relation of ocular trauma to cortical, nuclear, and posterior subcapsular cataracts was examined. Results: People with a history of ocular trauma were more likely to have cortical (odds ratio (OR): 1.5; 95% confidence interval (CI): 1.0 to 2.2) and posterior subcapsular (OR: 1.7; 95% CI: 1.0 to 3.1) cataracts, compared to people without a history of trauma. These associations were stronger for people with previous trauma caused by a blunt object (OR: 3.3; 95% CI: 1.6 to 6.9 for cortical cataract, and OR: 4.1; 95% CI: 1.5 to 10.8 for posterior subcapsular cataracts). However, in analyses comparing the frequencies of cataract between traumatised and non-traumatised eyes among people with unilateral ocular trauma, the ocular trauma association for cortical cataract was no longer present, although the association for posterior subcapsular cataract persisted (OR: 2.4; 95% CI: 0.8 to 7.8). Conclusion: The data provide evidence of a possible association between self reported ocular trauma and posterior subcapsular cataract.

Genetic Loci for Retinal Arteriolar Microcirculation

Abstract: Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value ,5610 28 . This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value=2.11610 212 in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.

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.