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.

Long-term use of aspirin and age-related macular degeneration.

Abstract: Context Aspirin is widely used for relief of pain and for cardioprotective effects. Its use is of concern to ophthalmologists when ocular surgery is being considered and also in the presence of age-related macular degeneration (AMD). Objective To examine the association of regular aspirin use with incidence of AMD. Design, Setting, and Participants The Beaver Dam Eye Study, a longitudinal population-based study of age-related eye diseases conducted in Wisconsin. Examinations were performed every 5 years over a 20-year period (1988-1990 through 2008-2010). Study participants (N = 4926) were aged 43 to 86 years at the baseline examination. At subsequent examinations, participants were asked if they had regularly used aspirin at least twice a week for more than 3 months. Main Outcome Measure Incidence of early AMD, late AMD, and 2 subtypes of late AMD (neovascular AMD and pure geographic atrophy), assessed in retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System. Results The mean duration of follow-up was 14.8 years. There were 512 incident cases of early AMD (of 6243 person-visits at risk) and 117 incident cases of late AMD (of 8621 person-visits at risk) over the course of the study. Regular aspirin use 10 years prior to retinal examination was associated with late AMD (hazard ratio [HR], 1.63 [95% CI, 1.01-2.63]; P = .05), with estimated incidence of 1.76% (95% CI, 1.17%-2.64%) in regular users and 1.03% (95% CI, 0.70%-1.51%) in nonusers. For subtypes of late AMD, regular aspirin use 10 years prior to retinal examination was significantly associated with neovascular AMD (HR, 2.20 [95% CI, 1.20-4.15]; P = .01) but not pure geographic atrophy (HR, 0.66 [95% CI, 0.25-1.95]; P = .45). Aspirin use 5 years (HR, 0.86 [95% CI, 0.71-1.05]; P = .13) or 10 years (HR, 0.86 [95% CI, 0.65-1.13]; P = .28) prior to retinal examination was not associated with incident early AMD. Conclusions Among an adult cohort, aspirin use 5 years prior to observed incidence was not associated with incident early or late AMD. However, regular aspirin use 10 years prior was associated with a small but statistically significant increase in the risk of incident late and neovascular AMD.

Women’s Ischemic Syndrome Evaluation Current Status and Future Research Directions: Report of the National Heart, Lung and Blood Institute Workshop: October 2–4, 2002: Section 5: Gender-Related Risk Factors for Ischemic Heart Disease

Abstract: The concomitant effects of aging, traditional risk factors, and a lack of endogenous estrogen promote the sequelae of arterial dysfunction, inflammation, and atheromatous plaque deposition in women. The challenges for improved diagnosis of coronary artery disease (CAD) in women include the more complex and multifactorial nature of the disease process; small artery size; and vascular and metabolic abnormalities that have yet to be thoroughly elucidated with existing imaging technology. Conditional risk markers, such as high-sensitivity C-reactive protein (hs-CRP), may provide greater insight into the arterial insult and underlying risk burden. Conventional ischemia testing, aimed primarily at detection of obstructive lesions, has provided disappointing results in women. Perhaps as a result of vascular remodeling, symptomatic women more often have nonobstructive atherosclerotic disease and, in some cases, evidence of metabolic or vascular dysfunction. Imaging accuracy in women is also hampered by technical problems and differences in body habitus. In addition, studies assessing diagnostic accuracy of imaging methods have often included small numbers of women subjects. In larger female samples, stress echocardiography and single photon emission computed tomography (SPECT) have yielded positive results in terms of estimating clinical outcomes. Newer technology, such as magnetic resonance spectroscopy (MRS) and perfusion imaging (MRI), has revealed intriguing findings indicating reductions in both subendocardial flow and high-energy phosphates that are suggestive of myocardial ischemia during stress testing in symptomatic women without obstructive CAD. This section reviews the evidence for gender differences in traditional and novel risk factors and explores the use of conventional and innovative myocardial methods to detect myocardial ischemia. ### Traditional Risk Factors The Atherosclerosis Risk In Communities (ARIC) study assessed traditional risks (age, cholesterol, blood pressure, smoking, and diabetes) for CAD events in 15 792 middle-aged, black and white women and men. These traditional risk factors can be integrated into a global risk score to predict 10-year risk …

Changes in abdominal obesity and age-related macular degeneration: the Atherosclerosis Risk in Communities Study.

Abstract: Objective To examine the association between changes in waist-hip ratio (WHR), a measure of abdominal obesity, and age-related macular degeneration (AMD). Methods A total of 12 515 persons from a population-based cohort study, aged 45 to 64 years in 1987 to 1989, were followed up over 6 years. The percentage change in WHR during follow-up was ranked into sex-specific deciles; an increase in WHR was defined as the top 10% of change and a decrease in WHR as the bottom 10%. The association of increased or decreased WHR and presence of AMD at follow-up was determined using logistic regression adjusting for potential confounders. Results The average change in WHR was an increase of 2%, ranging from a decrease of 44% to an increase of 102%. A decrease in WHR of 3% or more was associated with 29% lower odds of any AMD (odds ratio = 0.71; 95% confidence interval, 0.52-0.97). This effect was most pronounced among obese participants at baseline, where a decrease in WHR was associated with 59% lower odds of AMD (odds ratio = 0.41; 95% confidence interval, 0.20-0.82). Conclusions Middle-aged persons who had a 3% or greater reduction in WHR over time were less likely to have AMD, particularly among those who were initially obese.

Inhibition of EGF Signaling Protects the Diabetic Retina from Insulin-Induced Vascular Leakage

Abstract: Diabetes mellitus is a disease with considerable morbidity and mortality worldwide. Breakdown of the blood–retinal barrier and leakage from the retinal vasculature leads to diabetic macular edema, an important cause of vision loss in patients with diabetes. Although epidemiologic studies and randomized clinical trials suggest that glycemic control plays a major role in the development of vascular complications of diabetes, insulin therapies for control of glucose metabolism cannot prevent long-term retinal complications. The phenomenon of temporary paradoxical worsening of diabetic macular edema after insulin treatment has been observed in a number of studies. In prospective studies on non–insulin-dependent (type 2) diabetes mellitus patients, a change in treatment from oral drugs to insulin was often associated with a significant increased risk of retinopathy progression and visual impairment. Although insulin therapies are critical for regulation of the metabolic disease, their role in the retina is controversial. In this study with diabetic mice, insulin treatment resulted in increased vascular leakage apparently mediated by betacellulin and signaling via the epidermal growth factor (EGF) receptor. In addition, treatment with EGF receptor inhibitors reduced retinal vascular leakage in diabetic mice on insulin. These findings provide unique insight into the role of insulin signaling in mediating retinal effects in diabetes and open new avenues for therapeutics to treat the retinal complications of diabetes mellitus.

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.