Author
Frank E. Speizer
Other affiliations: Medical Research Council, Beth Israel Deaconess Medical Center, Washington University in St. Louis ...read more
Bio: Frank E. Speizer is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Relative risk & Risk factor. The author has an hindex of 193, co-authored 636 publications receiving 135891 citations. Previous affiliations of Frank E. Speizer include Medical Research Council & Beth Israel Deaconess Medical Center.
Papers published on a yearly basis
Papers
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TL;DR: The CYP19 gene codes for aromatase, a key steroidogenic enzyme involved in the conversion of androgens to estrogens, and a tetranucleotide (TTTA) repeat polymorphism, which is not close to the splice sites in intron 4, may explain the findings of an increased association between breast cancer and the 10 allele variant of CYp19.
Abstract: The CYP19 gene codes for aromatase, a key steroidogenic enzyme involved in the conversion of androgens to estrogens. A tetranucleotide (TTTA) repeat polymorphism is present in intron 4 of CYP19; 2 out of 4 breast cancer case-control studies have reported a greater frequency of 2 specific alleles among affected women. We evaluated associations between CYP19 repeat alleles and breast cancer risk in a case-control study nested within the Nurses' Health Study cohort (incident cases: n=462; controls: n=618). We observed seven different CYP19 alleles (TTTA(7-13)). Compared to controls, cases had a statistically significant greater frequency of the 10 (TTTA)(10) repeat allele (10 allele: 2.3% vs. 0.7%, p = 0.005) and a nonsignificant increase in the frequency of the 12 (TTTA)(12) allele (12 allele: 3.1% vs. 2.1%, p = 0.11). A higher frequency of the 10 allele was observed in more advanced cancer cases defined as four or more involved nodes or distant metastasis [4+ nodes: 5/36 (13.9%) vs. 0-3 nodes: 13/330 (3.9%), p = 0.02]. Among controls, we found women with the 7 repeat allele to have decreased levels of estrone sulfate (-16.4%, p = 0.02), estrone (-6.1%, p = 0.22) and estradiol (-9.9%, p = 0.10), and a lower estrone/androstenedione ratio (E1/A) (-10.5%, p = 0.08) compared to non-carriers. A higher E1/A ratio and elevated estrogen levels were observed among carriers of the 8 repeat allele; E1/A ratio (+21.0%, p = 0.003), estrone (+7.5%, p = 0.16) and estradiol (+10.8%, p = 0.08). However, we observed no evidence of an association between these alleles and breast cancer risk. We were unable to make inferences regarding the effect of the 10 allele on hormone levels due to the small number of allele carriers in the subgroup with hormone levels. As this repeat polymorphism is not close to the splice sites in intron 4, linkage disequilibrium with other functional polymorphisms in CYP19 may explain the findings of an increased association between breast cancer and the 10 allele variant of CYP19. We did not detect any sequence variants in the regulatory region or in the adipose-specific exon I.4. The lack of an established effect on CYP19 function associated with the 10 allele means that these findings should be interpreted with caution.
140 citations
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TL;DR: The hypothesis that height is inversely related to risk of coronary heart disease in women is supported by data from the Nurses' Health Study, a prospective cohort of 121,700 female nurses aged 30-55 years in 1976.
Abstract: Height has been inversely associated with coronary heart disease in several prospective studies in men, but data in women are sparse. The relation between height and cardiovascular disease was examined in 14 years of follow-up data from the Nurses' Health Study, a prospective cohort of 121,700 US female nurses aged 30-55 years in 1976. The relative risks associating height with coronary heart disease (nonfatal myocardial infarction (n = 1,000), fatal myocardial infarction (n = 304), confirmed angina (n = 1,343), or coronary revascularization (n = 901)) were estimated after adjustment for a large number of cardiovascular risk factors, including age and body mass index. Compared with the shortest women ( or = 1.70 m) tall (p for trend < 0.0001). The inverse association was more pronounced for angina/coronary revascularization (p for trend < 0.0001; relative risk for 67 or more inches = 0.67 (95% CI 0.58-0.78)) than for myocardial infarction (p for trend = 0.03; relative risk for 67 or more inches = 0.78 (95% CI 0.64-0.95)). No trend was evident for height in relation to risk of stroke. These data support the hypothesis that height is inversely related to risk of coronary heart disease in women.
139 citations
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TL;DR: Diagnosis of hypertension, higher BMI, and increasing pack-years of smoking appear to independently increase the risk of renal cell carcinoma.
Abstract: Objective:We prospectively investigated the independent association of hypertension, thiazide use, body mass index, weight change, and smoking with the risk of renal cell carcinoma among men and women using biennial mailed questionnaires.
139 citations
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TL;DR: Overall past use of oral contraceptives is not associated with a substantial increase in the risk of breast cancer, and women who used oral contraceptives for a long duration in early reproductive life was too small to permit firm conclusions regarding the risk.
Abstract: In 1976, 118,273 female nurses 30-55 years of age with no history of cancer completed a questionnaire regarding possible risk factors. By 1986, after 1,137,415 person-years of follow-up, we had documented 1,799 newly diagnosed cases of breast cancer. Compared with the risk of breast cancer for nonusers of oral contraceptives, the multivariate relative risks were 1.07 (95% confidence interval, 0.97-1.19) for all users, 1.06 (95% confidence interval, 0.96-1.18) for past users, and 1.53 (95% confidence interval, 1.06-2.19) for current users--women who used oral contraceptives up to 2 years before diagnosis of breast cancer. We conclude that overall past use of oral contraceptives is not associated with a substantial increase in the risk of breast cancer. Although we did not find women who used oral contraceptives before the first pregnancy to have an increased risk of breast cancer, the number of women who used oral contraceptives for a long duration in early reproductive life was too small to permit firm conclusions regarding the risk in this subgroup.
138 citations
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TL;DR: Greater dietary intake of certain meats and fats was associated with a higher risk of non-Hodgkin's lymphoma and their potential mechanisms deserve further examination.
Abstract: Background: Non-Hodgkin's lymphoma occurs more frequently in individuals with suppressed immune status, and some types of dietary fat and protein have been associated with decreased immune responses. In this study, we examined the intake of specific types of dietary fat and protein in relation to the risk of non-Hodgkin's lymphoma. Methods: We documented 199 incident cases of non-Hodgkin's lymphoma in a cohort of 88 410 women, who were enrolled in the Nurses' Health Study and were aged 34-60 years in 1980, during 14 years of follow-up. Relative risks of the disease and 95% confidence intervals (95% CIs) were calculated. All P values are two-sided and were considered to be statistically significant for P<.05. Results: Intake of saturated fat was associated with an increase in risk that was not statistically significant; the multivariate relative risk for the highest versus the lowest quintiles of intake was 1.4 (95% CI = 0.7-3.0; P for trend = .42). Intake of beef, pork, or lamb as a main dish was associated with a statistically significantly increased risk of non-Hodgkin's lymphoma; the multivariate relative risk for consumption of these meats at least once per day as compared with less than once per week was 2.2 (95% Cl = 1.1-4.4; P for trend =.002). Higher intake of trans unsaturated fat was also statistically significantly associated with an increased risk of the disease; the multivariate relative risk for the highest versus the lowest quintiles was 2.4 (95% CI = 1.3-4.6; P for trend =.01). Higher intake of red meat cooked by broiling or barbecuing-but not by roasting, pan-frying, or boiling or stewing-was associated with an increase in risk that was not statistically significant. Conclusions: Greater dietary intake of certain meats and fats was associated with a higher risk of non-Hodgkin's Iymphoma These relationships and their potentia mechanisms deserve further examination.
138 citations
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University of Manchester1, University of Barcelona2, St George's Hospital3, University of Marburg4, University of Texas Health Science Center at San Antonio5, Imperial College London6, University of Modena and Reggio Emilia7, University of Michigan8, Hokkaido University9, University of British Columbia10
TL;DR: It is recommended that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation.
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.
17,023 citations
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TL;DR: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Abstract: Context Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain Objective To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States Design Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 85 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998 Interventions Participants received conjugated equine estrogens, 0625 mg/d, plus medroxyprogesterone acetate, 25 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102) Main outcomes measures The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes Results On May 31, 2002, after a mean of 52 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits This report includes data on the major clinical outcomes through April 30, 2002 Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 129 (102-163) with 286 cases; breast cancer, 126 (100-159) with 290 cases; stroke, 141 (107-185) with 212 cases; PE, 213 (139-325) with 101 cases; colorectal cancer, 063 (043-092) with 112 cases; endometrial cancer, 083 (047-147) with 47 cases; hip fracture, 066 (045-098) with 106 cases; and death due to other causes, 092 (074-114) with 331 cases Corresponding HRs (nominal 95% CIs) for composite outcomes were 122 (109-136) for total cardiovascular disease (arterial and venous disease), 103 (090-117) for total cancer, 076 (069-085) for combined fractures, 098 (082-118) for total mortality, and 115 (103-128) for the global index Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures The absolute excess risk of events included in the global index was 19 per 10 000 person-years Conclusions Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 52-year follow-up among healthy postmenopausal US women All-cause mortality was not affected during the trial The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD
14,646 citations
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TL;DR: In this article, a randomized controlled trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly people was presented. But the authors did not discuss the effect of the combination therapy in patients living with systolic hypertension.
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 …
14,173 citations
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TL;DR: This research presents a novel and scalable approach called “Standardation of LUNG FUNCTION TESTing” that combines “situational awareness” and “machine learning” to solve the challenge of integrating nanofiltration into the energy system.
Abstract: [⇓][1]
SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING”
Edited by V. Brusasco, R. Crapo and G. Viegi
Number 2 in this Series
[1]: #F13
13,426 citations
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12,733 citations