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).

https://staff.blog.ui.ac.id/hsuryadi/files/2012/02/ROS_RNS.pdf

Free radicals and antioxidants in normal physiological functions and human disease

The metabolic syndrome has received increased attention in the past few years. This statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults.

The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors —that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).1 Patients with the metabolic syndrome also are at increased risk for developing type 2 diabetes mellitus. Another set of conditions, the underlying risk factors , give rise to the metabolic risk factors. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria to be used in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general they include a combination of both underlying and metabolic risk factors.

The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a pro-inflammatory state as well. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to which components of the syndrome are …

https://www.lipidcenter.com/pdf/metabolic.pdf

Diagnosis and Management of the Metabolic Syndrome An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

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).

Purpose: This study conducted confirmatory factor analysis (CFA) to examine the measurement structure of the Women’s Health Questionnaire (WHQ) and how its components were organized.Methods...

Hierarchical measurement structure in the Women's Health Questionnaire: a confirmatory factor analysis.

Barrington claims that the women’s health initiative (WHI) trial had impeccable standards1 We recently highlighted some of its shortcomings relating to hormone replacement therapy (HRT)2

The data and safety monitoring board used a global index of health which was modified on three occasions, including once after formal monitoring had started Although the oestrogen-progestogen arm of the studies was stopped after a designated safety boundary was breached, the oestrogen alone arm was stopped by staff of the National Heart, Lung and Blood Institute …

If only WHI was done well

Introduction: Physical activity is presumed to improve cardiovascular disease (CVD), of which carotid artery intima-media thickness (CIMT) is a common indicator. Individuals with spinal cord injury (SCI) have limited mobility and therefore an expected increased risk for CVD. The purpose of this study was to determine which CVD risk factors predict CIMT among women with SCI, with the ultimate goal of targeting therapy to improve CVD in this population. Methods: One hundred twenty-two women with SCI who attended an outpatient SCI clinic and met inclusion and exclusion criteria participated in this study. SCI was categorized into 1 of 4 categories: complete tetraplegia, incomplete tetraplegia, complete paraplegia, and incomplete paraplegia. Maximum heart rate and VO2 max were obtained using bicycle ergometry with ventilatory gas exchange and continuous electrocardiogram. Hierarchical regression was used to predict CIMT, with the first block including demographic variables (age, race, smoking status) and the second block including physiologic variables (total cholesterol, heart rate, VO2 max, BMI, fasting serum glucose, hemoglobin A1c, and blood pressure). Results: Similar findings were observed for left and right CIMT, therefore only results from right CIMT are reported. The overall model was significant, F(16,46)=8.53, p=.000. Adjusted R square was .54 for the first block of variables and increased significantly (p=.006) to .66 when the second block of variables was added. Significant predictors at alpha=.05 included age (beta=.51, t=4.79, p=.000) and max/peak heart rate (beta=−.336, t=−2.39, p=.02). At alpha=.10, A1c was significant (beta=.187, t=1.99, p=.053). Conclusions: Although low aerobic conditioning is a purported CVD risk factor, quantitative measurements of such lack a demonstrable relationship with subclinical atherosclerosis (CIMT), perhaps because of its reduced importance relative to other CVD risk factors in a mobile population. We found expected relationships with CIMT in our SCI population (i.e., age), however we also found a quantitative measure of aerobic conditioning (max/peak heart rate) to be associated with CIMT. Our data indicate that SCI individuals may bear a greater CVD burden from cardiac de-conditioning than the general population and that investigation of a cohort with mobility limitation may provide a unique opportunity to study the impact of physical conditioning on CVD risk.

Abstract P313: De-Conditioning Adversely Affects Subclinical Atherosclerosis in a Unique Cohort of Spinal Cord Injury

Publisher Summary There is now serial angiographic evidence for atherosclerotic lesion improvement induced by diverse modes of intervention. The weight of evidence indicates that atherosclerotic lesions as well as clinical coronary events are reduced by intervention. The Cholesterol-Lowering Atherosclerosis Study (CLAS) gave the first clear indication of the importance of triglyceride-rich lipoproteins in lesion progression-an effect manifested after LDL-C was removed as a risk factor. Although clinical events were not significantly different between drug and placebo groups during the 2 years of intervention, 10 year follow-up indicates a significantly lower clinical coronary event rate in the drug group. This chapter concentrates on familial atherosclerosis treatment study (FATS), NHLBl type II coronary intervention study, cholesterol-lowering atherosclerosis study (CLAS), research intervention trials, monitored atherosclerosis regression study (MARS), multicentre anti-atheroma study (MAAS), Heidelberg exercise-diet study, and the program on the surgical control of the hyperlipidemias (POSCH). Many interesting and important findings have resulted from coronary angiographic trials that need further attention if it is to increase our success with secondary preventive measures. The majority of the coronary angiographic trials, NHLBI Type II, CLAS, FATS, STARS, MARS, CCAIT, MAAS, Leiden Intervention Trial, and Lifestyle Heart Trial indicate that LDL-C reduction preferentially regresses lesions 250%S and typically retards coronary artery lesion progression in only 50 to 80% of subjects. Improved therapeutic regimens to alter progression of coronary atherosclerosis may require adjunctive therapy in concert with LDL-C reduction to prevent new lesion formation or to induce early lesion regression, such as for lesions

Reversal of atherosclerosis with therapy: update of coronary angiographic trials.

We thank Wang et al for their commentary regarding our recently published article relating childhood O3 exposure to carotid intima–media thickness (CIMT) in adulthood.1 The authors suggest that adjustment for additional clinical information may strengthen our conclusion regarding O3 as a novel predictor of CIMT. Specifically, they suggest we include data on childhood dietary patterns, adolescent blood pressure (BP), and glucose tolerance testing. Although we agree that these data are relevant clinical parameters when assessing cardiovascular disease risk and atherosclerosis, it is unlikely that they will act as confounders of our observed association with O3 if they are not related to exposure.

First, the evaluation of elementary and lifetime diet, as suggested by the authors, is a daunting task, and one highly susceptible to recall bias. Most food frequency questionnaires are designed to address recall only …

Howard N. Hodis

Papers

Hierarchical measurement structure in the Women's Health Questionnaire: a confirmatory factor analysis.

If only WHI was done well

Abstract P313: De-Conditioning Adversely Affects Subclinical Atherosclerosis in a Unique Cohort of Spinal Cord Injury

Reversal of atherosclerosis with therapy: update of coronary angiographic trials.

Response to Letter Regarding Article, “Childhood Air Pollutant Exposure and Carotid Artery Intima–Media Thickness in Young Adults”