There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Importance Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. Objective To evaluate and, as needed, update definitions for sepsis and septic shock. Process A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Key Findings From Evidence Synthesis Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Recommendations Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. Conclusions and Relevance These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

https://jamanetwork.com/journals/jama/articlepdf/2492881/jsc160002.pdf

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

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://caltcm.memberclicks.net/assets/documents/acc_aha_chf_2013_guidelines.pdf

2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines

https://hull-repository.worktribe.com/preview/1797952/1-s2.0-S0140673618322797-main.pdf

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

/pdf/the-efficacy-of-hormonal-therapy-for-reducing-coronary-1czzbrt7ao.pdf

The Efficacy of Hormonal Therapy for Reducing Coronary Artery Disease in Women

http://www.onlinecjc.ca/article/S0828282X23001782/pdf

Increased Left Ventricular Ejection Fraction in Women with Ischemia But No Obstructive Coronary Artery Disease: Novel insight from Strain Imaging


 
 
 Ischemia with no obstructed coronary arteries (INOCA) is prevalent among women and associated with an increased risk of developing heart failure with preserved ejection fraction (HFpEF), however the mechanism linking these conditions remains poorly understood. Coronary vascular dysfunction is common in INOCA, representing a putative mechanism driving heart failure progression.
 
 
 
 To evaluate the role of coronary vascular dysfunction on left ventricular (LV) function in women with INOCA.
 
 
 
 Women with suspected INOCA, defined as having signs and symptoms of ischemia but no obstructive coronary artery disease, underwent LV pressure-volume assessment at rest and during 3 minutes of isometric handgrip stress at 30% of maximal voluntary contraction. Coronary function testing was performed by infusing standard doses of adenosine, acetylcholine, and nitroglycerine through a guiding catheter placed in the left main coronary artery, per our published protocols. Using standardized definitions of normal versus abnormal responses, cases with zero abnormal coronary pathways (n=12) were compared to cases with three abnormal coronary pathways (n=7).
 
 
 
 At rest, end-systolic pressure and end-systolic elastance were elevated in cases with abnormal coronary vascular function (Figure), while normalized peak filling rate was lower (0.45±0.15 s mmHg–1 vs 0.37±0.08 s mmHg–1). With isometric handgrip, end-systolic pressure and end-systolic elastance increased similarly between groups, remaining highest in those with abnormal coronary vascular function (Figure). End-diastolic pressure-volume declined with handgrip in those without coronary vascular dysfunction, while increasing (up and to the left) in those with coronary vascular dysfunction (Figure). Likewise, normalized peak filling rate improved with handgrip in those without coronary vascular dysfunction, but did not change in those with coronary vascular dysfunction (0.66±0.37 s mmHg–1 vs 0.38±0.15 s mmHg–1).
 
 
 
 We show heightened ventricular and vascular stiffness in women with INOCA who have abnormal coronary vascular function. These preliminary data support the hypothesis that coronary vascular dysfunction may be a putative mechanistic pathway driving heart failure progression in INOCA.
 
 
 
 Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health


Ventricular and vascular stiffening in ischemia with no obstructed coronary arteries: novel insight from pressure-volume analysis

Management of patients with persistent angina and no obstructive coronary artery disease continues to be a challenging area. Currently, pharmacotherapy used in patients with microvascular coronary dysfunction (MCD) is targeted at their underlying mechanism for pain. Therapies used in patients with coronary artery disease such as nitrates, β-blockers, calcium channel blockers, and statins have also been found to be beneficial in those with MCD. Other agents found to have promising effects on anginal symptoms includes ranolazine and angiotensin converting enzyme inhibitors. Hormone therapy in women with MCD improves quality of life, although improvement in myocardial ischemia remains to be determined. In patients with cardiac syndrome X, small trials have been performed showing either beneficial or indeterminate results with the use of other pharmacologic agents such as tricyclic medications, L-arginine, xanthine derivatives, n-3 polyunsaturated fatty acids, nicorandil, and trimetazidine. Non-pharmacologic therapies in the management of chronic angina also play an important role. Lifestyle modification, exercise, and cognitive behavioral therapy have shown to improve angina and exercise capacity in those with MCD. The use of neurostimulation, including transcutaneous electrical nerve stimulation and spinal cord stimulation, can also improve symptoms in those with chronic angina. Incorporating both pharmacologic and non-pharmacological therapies can lead to the effective management of chronic angina in patients with MCD.

Management of Pain

Background: Pregnancy is associated with physiological changes to meet the metabolic demands of the growing fetus. To understand adverse pregnancy outcomes it is important to establish vascular changes throughout pregnancy. We examined longitudinal changes in vascular measurements from prepregnancy through postpartum. Materials and Methods: Seventy women planning to conceive in Ulaanbaatar, Mongolia enrolled in this prospective study. Within 6 months, 44 (63%) had conceived; of which 36 (82%) delivered. Ten (28%) developed complex pregnancies and were analyzed separately. Vascular measures included central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), augmentation index corrected for heart rate of 75 beats/minute (AIx-75), and pulse wave velocity (PWV). Measurements were performed at prepregnancy, second trimester (22-24 weeks), third trimester (34-36 weeks), and 2 months postpartum. Missing values (n = 0-6 per time period) were replaced by multiple imputation. A repeated measures analysis of variance analyzed changes within individual women over the four time points adjusted for age, parity, and body mass index. Results: We observed significant reductions from prepregnancy to second trimester for mean Alx-75 (17.1%-12.6%; p = 0.006) and cSBP (91.7-86.8 mmHg; p = 0.03) but not for cDBP or PWV. Both mean AIx-75 and cSBP increased in third trimester. In the postpartum, cSBP returned to prepregnancy levels, whereas AIx-75 exceeded prepregnancy levels, although this fell short of significance (p = 0.09). Similar vascular patterns were observed in women with complex pregnancies for AIx-75; however, PWV increased from the second trimester and remained higher through postpartum, although not significant. Conclusion: In Mongolian women, we observed a decrease in AIx-75 and cSBP from prepregnancy through second trimester, which resolved postpartum. These results provide an understanding of changes across pregnancies in an Asian country. Future studies should assess vascular changes across pregnancies to determine if it can predict conditions such as pre-eclampsia.

C. Noel Bairey Merz

Papers

The Efficacy of Hormonal Therapy for Reducing Coronary Artery Disease in Women

Increased Left Ventricular Ejection Fraction in Women with Ischemia But No Obstructive Coronary Artery Disease: Novel insight from Strain Imaging

Ventricular and vascular stiffening in ischemia with no obstructed coronary arteries: novel insight from pressure-volume analysis

Management of Pain

Changes in Vascular Function from Preconception to Postpartum Among Mongolian Women.