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.

Medication use and the 5-year incidence of early age-related maculopathy: the Beaver Dam Eye Study.

Abstract: Objective To evaluate incident early age-related maculopathy (ARM) after a 5-year interval with respect to medication use. Design Population-based incidence study. Setting Participants were adults aged 43 to 86 years living in Beaver Dam, Wis, when first examined in 1988-1990 (n = 4926); they were reexamined in 1993-1995(n = 3684). Methods All participants were examined and interviewed and stereoscopic color fundus photographs were taken. All procedures were done by standard protocol at both examinations. Incidence of ARM was based on grading using the Wisconsin ARM Grading System. All prescribed and over-the-counter medications in current use were brought to the examination site and the names were recorded at that time. Results There were 678 drug preparations (active ingredients) being used at the baseline examination. No relations were found between most antihypertensive drugs, most central nervous system medications, aspirin and other nonsteroidal anti-inflammatory agents, estrogens, lipid-lowering agents, and incident early ARM over the 5-year period. Age- and sex-adjusted logistic regression analyses suggested possible associations ( P P = .06), desiccated thyroid hormones (OR, 2.32; 95% CI, 0.89-6.07; P = .09), and calcium channel blockers (OR, 1.70; 95% CI, 0.93-3.12; P = .08) with incident ARM. When additional information on past use was included in the regression model, the association remained for calcium channel blockers, but not for phenothiazines and desiccated thyroid hormones. A lower incidence of early ARM occurred in those who took antidepressants(OR, 0.34; 95% CI, 0.12-0.94; P = .04) at the baseline examination. Conclusion Although many different medications were being used at the baseline examination in the Beaver Dam Eye Study cohort, there were no striking associations with the 5-year incidence of early ARM.

The role of genetics in susceptibility to diabetic retinopathy.

Abstract: Diabetic retinopathy remains the leading cause of blindness in working-aged adults.(1) Over 4 million adults 40 years and older in the United States are estimated to have diabetic retinopathy, of whom 1 out of every 12 has advanced vision-threatening retinopathy (2). With the projected increase in the world-wide prevalence of diabetes to 380 million people by 2025,(3;4) of whom 40% are expected to have some form of diabetic retinopathy,(2) there is a clearly a need to develop strategies to identify persons at risk of diabetic retinopathy, allowing prevention and early intervention. Risk Factors for Diabetic Retinopathy There is already strong evidence that longer duration of diabetes, poorer control of blood glucose and elevated blood pressure are the major factors responsible for the onset and progression of diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a population-based cohort study of diabetes in which participants were first examined in 1980-82, showed that in persons with type 1 diabetes, the prevalence of diabetic retinopathy ranged from 17% in those with diabetes for less than 5 years to almost 100% in those with diabetes for over 15 years.(5) The corresponding figures in persons with type 2 diabetes were 29% and 78%.(6) The importance of good glycemic control for delaying the development and progression of diabetic retinopathy was confirmed in two landmark clinical trials, the Diabetes Control and Complications Trial (DCCT) in persons with type 1 diabetes,(7) and the UK Prospective Diabetes Study (UKPDS) in persons with type 2 diabetes.(8) The UKPDS has further shown the value of tight blood pressure control in delaying the development of diabetic retinopathy complications and well as other microvascular endpoints.(9;10) More recently, the Fenofibrate Intervention and Event Lowering in Diabetes Study(11) indicated that lipid lowering therapy might reduce retinopathy requiring laser treatment. Nonetheless, diabetic retinopathy occurs even with optimal glucose and blood pressure control. The newly completed ADVANCE trial recruited 11,140 patients with type 2 diabetes and found intensive glucose control to reduce glycosylated hemoglobin to 6.5% or lower had no effect on the 5-year incidence of retinopathy rates. ADVANCE also reported that lowering of blood pressure to near normal levels (approximately 140/80) did not achieve further reduction in progression of diabetic retinopathy.(12) In addition, it is clinically apparent that some patients with poor control of glycemia or blood pressure do not develop diabetic retinopathy even over prolonged periods of time, while others may develop diabetic retinopathy in relatively short periods of time despite good risk factor control. This was prominently illustrated in the Joslin Medalist study which found that almost 50% of older diabetic participants in their study had no evidence of retinopathy despite surviving over 50 years with type 1 diabetes.(13) Finally, a recent observational study of 11,423 participants from three diverse populations,(14) reported that retinopathy signs, mainly retinal microaneurysms, characteristic of diabetes were detectable in 7.4-13.4% of nondiabetic participants, and were present even in individuals with glycosylated hemoglobin levels <5.0%. These results suggest that processes other than hyperglycemia and elevated blood pressure contribute to the development and progression of diabetic retinopathy.

Association of dietary and life-style factors with sex hormones in postmenopausal women.

Abstract: We examined the relations between endogenous sex hormones and alcohol intake, dietary constituents, and life-style factors in a population-based sample of 253 postmenopausal women not using replacement hormones. Estrone, dihydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), and free and total testosterone were measured in serum. Age and years since menopause were negatively associated with dihydroepiandrosterone sulfate and positively associated with sex hormone-binding globulin levels. Higher relative weight was strongly and negatively associated with sex hormone-binding globulin. Other factors were only very weakly associated with sex hormones. Since, except for weight, few potentially modifiable factors appear to influence these hormone profiles, it may be that behaviors earlier in life mediate hormone levels and subsequent disease risk.

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.