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

/pdf/risks-and-benefits-of-estrogen-plus-progestin-in-healthy-4glim99n2t.pdf

Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial

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 …

/pdf/2013-esh-esc-guidelines-for-the-management-of-arterial-4ydvs5ifsx.pdf

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).

Guidelines are inconsistent in how they rate the quality of evidence and the strength of recommendations. This article explores the advantages of the GRADE system, which is increasingly being adopted by organisations worldwide

/pdf/grade-an-emerging-consensus-on-rating-quality-of-evidence-ft3aqcsyh5.pdf

GRADE: an emerging consensus on rating quality of evidence and strength of recommendations

2007 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).

Although considerable improvement has occurred in the process of care for patients with ST-elevation myocardial infarction (STEMI), room for improvement exists.[1–3][1][][2][][3] The purpose of the present guideline is to focus on the numerous advances in the diagnosis and management of patients

/pdf/acc-aha-guidelines-for-the-management-of-patients-with-st-3d4n2zt04k.pdf

ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction—Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction)

Our objective is to illustrate the bias introduced in assessing factors associated with age at menopause when the population sample has been selected using restricted criteria, i.e. number of years since menopause, by using a cross-sectional analysis of baseline data from a population-based randomized clinical trial. The participants were women who participated in the Postmenopausal Estrogen/Progestins Intervention (PEPI) trial, had not had a hysterectomy, were between 45 and 64 years old, and were menopausal for at least 1 but not greater than 10 years. The outcome measures were self-reported age at menopause and factors thought to be associated with it, including smoking, alcohol use, oral contraceptive use, number of pregnancies, education, income, body mass index, waist-hip ratio, thigh girth, and systolic and diastolic blood pressures. At entry, the mean age of the 601 women was 56.2 years. Mean age at menopause was 51.0 years. Chronologic (current) age was strongly correlated with age at menopause (r = 0.74, p = 0.0001). In bivariate analyses, factors associated with younger age at menopause were ever-use of cigarettes, former oral contraceptive use, and higher thigh girth; factors associated with later age at menopause were greater number of pregnancies, higher waist-hip ratio, and higher systolic blood pressure. After stratification by 5-year age intervals, these associations were no longer statistically significant. Because of restricted sampling, an artificial association was observed between chronologic age and age at time of menopause. This artifact made it difficult to distinguish between factors associated with chronologic age and those that may be independently associated with menopause. Failure to recognize this bias could lead to erroneous conclusions.

Age at menopause in women participating in the postmenopausal estrogen/progestins interventions (PEPI) trial: An example of bias introduced by selection criteria

Smoking status and sociodemographic characteristics were recorded for 23,572 white women 25-74 years of age in a private census of Washington County, Maryland, done in 1963. Deaths from all causes, from total and sudden arteriosclerotic heart disease, and with stroke were recorded for the next 12 years. Smoking-specific mortality rates for women aged 25-44, 45-64, and 65-74 years at entry were calculated after adjustment for the effects of marital status, education, housing quality, and frequency of church attendance. Among women in the 65-74-year age group, smoking was not related to mortality. Among women in the two younger age groups, the risks of dying from any cause and from arteriosclerotic heart disease (total and sudden) were positively associated with cigarette smoking. For all arteriosclerotic heart disease deaths, the relative risks associated with smoking more than 20 cigarettes a day were 3.6 and 2.2 for women aged 25-44 and 45-64, respectively; for sudden deaths from arteriosclerotic heart disease, the relative risks were 6.5 and 2.7. The risk of dying with stroke was not associated with cigarette smoking.

Smoking and cardiovascular mortality in women

Hormone replacement therapy and risk of breast cancer.

Data from cross-sectional surveys show an increase in systolic blood pressure with increasing age. However, cross-sectional data can be misleading. Our purpose in this study is to prospectively describe changes in systolic and diastolic blood pressure levels over time in community-dwelling elderly persons. The participants were 1, 917 men and women aged 65 to 98 yr who had participated at least seven years in the Florida Geriatric Research Program, a community-based, multi-phasic health screening program located in Dunedin, Florida (USA). Our results show that contrary to the cross-sectional data, systolic and diastolic blood pressure levels tend to decrease with increasing age. Mean systolic blood pressure in women at the baseline visit (Visit 2) was 143 mmHg and three years later (Visit 5) it had dropped to 140 mmHg. This downward trend was consistent at all ages and for both men and women. Stratification by use of antihypertensive medication, weight change, and survivorship did not alter this association. Further follow-up of this cohort to Visit 7 revealed a U-shaped trend of blood pressure with aging. There was also clear evidence of a cohort effect, as the age-specific mean systolic blood pressure was consistently lower in each younger 5 yr birth cohort. Our results suggest that in a healthy elderly population, systolic and/or diastolic blood pressure levels do not increase with aging; this finding may have implications for the diagnosis and treatment of hypertension in the elderly.

Trudy L. Bush

Papers

Age at menopause in women participating in the postmenopausal estrogen/progestins interventions (PEPI) trial: An example of bias introduced by selection criteria

Smoking and cardiovascular mortality in women

Hormone replacement therapy and risk of breast cancer.

Blood pressure changes with aging: evidence for a cohort effect.

The epidemiology of cardiovascular disease in older persons.