Debbie A Lawlor

Bio: Debbie A Lawlor is an academic researcher from University of Bristol. The author has contributed to research in topics: Population & Body mass index. The author has an hindex of 147, co-authored 1114 publications receiving 101123 citations. Previous affiliations of Debbie A Lawlor include Southampton General Hospital & University of Vermont.

The Association of Smoking and Cardiovascular Disease in a Population With Low Cholesterol Levels: A Study of 648 346 Men From the Korean National Health System Prospective Cohort Study

Abstract: Background and Purpose— The association of smoking with cardiovascular diseases in populations with low cholesterol levels is unclear and this lack of clarity may have contributed to the very high prevalence of smoking in East Asian men. The effect of smoking on stroke subtypes is particularly unclear. Methods— We used data from a prospective cohort study of 648 346 Korean men aged 30 to 64 years at their baseline assessment in 1992. Results— Mean (SD) total cholesterol at baseline was 4.9 (1.0) mmol/L and 59% of the men were current smokers. Over the follow-up period of 10 years, 9475 men experienced any type of stroke, 4768 experienced an ischemic stroke, 2380 an intracerebral hemorrhage, 786 a subarachnoid hemorrhage, 3329 men experienced a myocardial infarction, and 269 an aortic aneurysm. Smoking at baseline was associated with marked increases in risk of ischemic stroke (hazard ratio comparing current smokers with never smokers 1.58 [95% CI: 1.49 to 1.68]), subarachnoid hemorrhage (1.91 [1.63 to 2.2...

The effect of a lifestyle intervention in obese pregnant women on gestational metabolic profiles: findings from the UK Pregnancies Better Eating and Activity Trial (UPBEAT) randomised controlled trial

Abstract: Pregnancy is associated with widespread change in metabolism, which may be more marked in obese women. Whether lifestyle interventions in obese pregnant women improve pregnancy metabolic profiles remains unknown. Our objectives were to determine the magnitude of change in metabolic measures during obese pregnancy, to indirectly compare these to similar profiles in a general pregnant population, and to determine the impact of a lifestyle intervention on change in metabolic measures in obese pregnant women. Data from a randomised controlled trial of 1158 obese (BMI ≥ 30 kg/m2) pregnant women recruited from six UK inner-city obstetric departments were used. Women were randomised to either the UPBEAT intervention, a tailored complex lifestyle intervention focused on improving diet and physical activity, or standard antenatal care (control group). UPBEAT has been shown to improve diet and physical activity during pregnancy and up to 6-months postnatally in obese women and to reduce offspring adiposity at 6-months; it did not affect risk of gestational diabetes (the primary outcome). Change in the concentrations of 158 metabolic measures (129 lipids, 9 glycerides and phospholipids, and 20 low-molecular weight metabolites), quantified three times during pregnancy, were compared using multilevel models. The role of chance was assessed with a false discovery rate of 5% adjusted p values. All very low-density lipoprotein (VLDL) particles increased by 1.5–3 standard deviation units (SD) whereas intermediate density lipoprotein and specific (large, medium and small) LDL particles increased by 1–2 SD, between 16 and 36 weeks’ gestation. Triglycerides increased by 2–3 SD, with more modest changes in other metabolites. Indirect comparisons suggest that the magnitudes of change across pregnancy in these obese women were 2- to 3-fold larger than in unselected women (n = 4260 in cross-sectional and 583 in longitudinal analyses) from an independent, previously published, study. The intervention reduced the rate of increase in extremely large, very large, large and medium VLDL particles, particularly those containing triglycerides. There are marked changes in lipids and lipoproteins and more modest changes in other metabolites across pregnancy in obese women, with some evidence that this is more marked than in unselected pregnant women. The UPBEAT lifestyle intervention may contribute to a healthier metabolic profile in obese pregnant women, but our results require replication. UPBEAT was registered with Current Controlled Trials, ISRCTN89971375 , on July 23, 2008 (prior to recruitment).

Association of maternal circulating 25(OH)D and calcium with birth weight: A mendelian randomisation analysis.

Abstract: Background Systematic reviews of randomised controlled trials (RCTs) have suggested that maternal vitamin D (25[OH]D) and calcium supplementation increase birth weight. However, limitations of many trials were highlighted in the reviews. Our aim was to combine genetic and RCT data to estimate causal effects of these two maternal traits on offspring birth weight. Methods and findings We performed two-sample mendelian randomisation (MR) using genetic instrumental variables associated with 25(OH)D and calcium that had been identified in genome-wide association studies (GWAS; sample 1; N = 122,123 for 25[OH]D and N = 61,275 for calcium). Associations between these maternal genetic variants and offspring birth weight were calculated in the UK Biobank (UKB) (sample 2; N = 190,406). We used data on mother–child pairs from two United Kingdom birth cohorts (combined N = 5,223) in sensitivity analyses to check whether results were influenced by fetal genotype, which is correlated with the maternal genotype (r ≈ 0.5). Further sensitivity analyses to test the reliability of the results included MR-Egger, weighted-median estimator, ‘leave-one-out’, and multivariable MR analyses. We triangulated MR results with those from RCTs, in which we used randomisation to supplementation with vitamin D (24 RCTs, combined N = 5,276) and calcium (6 RCTs, combined N = 543) as an instrumental variable to determine the effects of 25(OH)D and calcium on birth weight. In the main MR analysis, there was no strong evidence of an effect of maternal 25(OH)D on birth weight (difference in mean birth weight −0.03 g [95% CI −2.48 to 2.42 g, p = 0.981] per 10% higher maternal 25[OH]D). The effect estimate was consistent across our MR sensitivity analyses. Instrumental variable analyses applied to RCTs suggested a weak positive causal effect (5.94 g [95% CI 2.15–9.73, p = 0.002] per 10% higher maternal 25[OH]D), but this result may be exaggerated because of risk of bias in the included RCTs. The main MR analysis for maternal calcium also suggested no strong evidence of an effect on birth weight (−20 g [95% CI −44 to 5 g, p = 0.116] per 1 SD higher maternal calcium level). Some sensitivity analyses suggested that the genetic instrument for calcium was associated with birth weight via exposures that are independent of calcium levels (horizontal pleiotropy). Application of instrumental variable analyses to RCTs suggested that calcium has a substantial effect on birth weight (178 g [95% CI 121–236 g, p = 1.43 × 10−9] per 1 SD higher maternal calcium level) that was not consistent with any of the MR results. However, the RCT instrumental variable estimate may have been exaggerated because of risk of bias in the included RCTs. Other study limitations include the low response rate of UK Biobank, which may bias MR estimates, and the lack of suitable data to test whether the effects of genetic instruments on maternal calcium levels during pregnancy were the same as those outside of pregnancy. Conclusions Our results suggest that maternal circulating 25(OH)D does not influence birth weight in otherwise healthy newborns. However, the effect of maternal circulating calcium on birth weight is unclear and requires further exploration with more research including RCT and/or MR analyses with more valid instruments.

Influence of area and individual lifecourse deprivation on health behaviours: findings from the British Women's Heart and Health Study

Abstract: BackgroundVariable findings have been reported on the contribution of census-based measures of area deprivation over and above that of individual socioeconomic position (SEP) on health outcomes. This study aims to examine the association between residence in a deprived area and health behaviours (diet, smoking and physical inactivity), and how this association is influenced by lifecourse SEP of individuals.DesignA population-based longitudinal study of women aged 60-79 years in 1999-2001 recruited from one general practice in each of 23 British towns.MethodsThree thousand five hundred twenty-two women were included in the analyses. Area deprivation scores were derived from postcode for residence and lifecourse SEP scores were calculated using 10 individual level indicators of childhood and adult circumstances. To allow direct comparisons of effect of area deprivation and individual SEP, we standardized both measures by generating relative indices of inequality.ResultsBoth area deprivation and lifecourse S...

Body mass index in middle life and future risk of hospital admission for psychoses or depression: findings from the Renfrew/Paisley study.

Abstract: Background. There is evidence that greater body mass index (BMI) protects against depression, schizophrenia and suicide. However, there is a need for prospective studies. Method. We examined the association of BMI with future hospital admissions for psychoses or depression/anxiety disorders in a large prospective study of 7036 men and 8327 women. Weight and height were measured at baseline (1972-76) when participants were aged 45-64. Follow-up was for a median of 29 years. Results. Greater BMI and obesity were associated with a reduced risk of hospital admission for psychoses and depression/anxiety in both genders, with the magnitude of these associations being the same for males and females. With adjustment for age, sex, smoking and social class, a I standard deviation (S.D.) greater BMI at baseline was associated with a rate ratio of 0.91 [95 % confidence interval (CI) 0.82-1.01] for psychoses and 0.87 (95 % CI 0.77-0.98) for depression/anxiety. Further adjustment for baseline psychological distress and total cholesterol did not alter these associations. Conclusions. Our findings add to the growing body of evidence that suggests that greater BMI is associated with a reduced risk of major psychiatric outcomes. Long-term follow-up of participants in randomized controlled trials of interventions that effectively result in weight loss and the use of genetic variants that are functionally related to obesity as instrumental variables could help to elucidate whether these associations are causal.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Abstract: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

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 …