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).

Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes. There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes. Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/1791497/jsc130010.pdf

2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)

This article reviews the burgeoning literature on the relationship of mood disorders and heart disease. Major depression and depressive symptoms, although commonly encountered in medical populations, are frequently underdiagnosed and undertreated in patients with cardiovascular disease (CVD). This is of particular importance because several studies have shown depression and its associated symptoms to be a major risk factor for both the development of CVD and death after an index myocardial infarction. This review of the extant literature is derived from MEDLINE searches (1966-1997) using the search terms "major depression," "psychiatry," "cardiovascular disease," and "pathophysiology." Studies investigating pathophysiological alterations related to CVD in depressed patients are reviewed. The few studies on treatment of depression in patients with CVD are also described. Treatment of depression in patients with CVD improves their dysphoria and other signs and symptoms of depression, improves quality of life, and perhaps even increases longevity. Recommendations for future research are proposed.

The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment.

1993 Guidelines for the management of mild hypertension: Memorandum from a World Health Organization/International Society of Hypertension meeting

http://cardiology.org/recentpapers/sumetgl02.pdf

Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines)

In 31 patients with essential hypertension there was a close relation between resting diastolic blood pressure and basal plasma norepinephrine concentrations (r = 0.741, p < 0.001). After ganglionic blockade there was a highly significant correlation between change in resting blood pressure and change in plasma norepinephrine (r = 0.813, p < 0.001). Moreover, patients with the highest resting blood pressure had the largest falls in blood pressure and plasma norepinephrine. These results suggest that the level of the blood pressure in essential hypertension is at least in part dependent on excess sympathetic activity.

https://www.nejm.org/doi/pdf/10.1056/NEJM197303222881203?listPDF=true

Plasma Norepinephrine Levels in Essential Hypertension

Smoking as a risk factor for cerebral ischaemia.

http://www.clinsci.org/content/ppclinsci/63/s8/431s.full.pdf

Australian Therapeutic Trial in Mild Hypertension

Streptozotocin (STZ) diabetes was induced in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Body weight, blood pressure, renal function, glycaemic control and proteinuria were assessed monthly for 32 weeks. At 32 weeks, the animals were killed and glomerular basement membrane (GBM) thickness and fractional mesangial volume were measured. There was no significant difference in renal function between diabetic SHR and diabetic WKY. Diabetic SHR showed an earlier and larger rise in total proteinuria and urinary albumin excretion than diabetic WKY. Urinary albumin excretion was increased more than tenfold in diabetic SHR compared to diabetic WKY after 32 weeks of diabetes. GBM thickness was significantly increased in diabetic SHR compared with diabetic WKY. Both diabetic WKY and diabetic SHR showed mesangial expansion when compared to their nondiabetic counterparts. On the other hand, both hypertensive models showed increased glomerular volume, which was not influenced by the presence of diabetes. The diabetic SHR model has features of accelerated nephropathy, as evidenced by increased albuminuria and GBM thickness. This suggests that pre-existing hypertension may play an important role in the progression of diabetic renal disease.

Effects of genetic hypertension on diabetic nephropathy in the rat--functional and structural characteristics.

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats aged 4 and 16 weeks were given an acute oral dose of either Perindopril (3 mg/kg) or vehicle. Direct blood pressure (BP), glomerular filtration rate (GFR) and renal blood flow (RBF) were measured, and renal vascular resistance (RVR) calculated. GFR and RBF were lower in vehicle-treated SHR than WKY at 4 weeks of age, but were not different at 16 weeks. Acute Perindopril increased GFR and RBF and reduced RVR in both strains at both 4 and 16 weeks. Total body sodium, sodium intake and blood pressure were measured in SHR and WKY from 1 to 28 weeks of age. Rats of both strains were treated daily between 4 and 16 weeks of age with either Perindopril (3 mg/kg per day) or vehicle. Chronic Perindopril treatment prevented the development of hypertension in the SHR. From 16 to 28 weeks of age, after stopping Perindopril, BP rose slowly in SHR, but remained lower than vehicle-treated SHR. No changes in total body sodium occurred during Perindopril treatment. GFR and RBF were measured in SHR and WKY chronically treated with either Perindopril or vehicle, 3 days or 12 weeks after stopping treatment. In WKY, GFR and RBF were not different between Perindopril-treated and untreated rats at either measurement. In SHR, GFR and RBF remained significantly higher in rats previously treated with Perindopril at both ages. These findings suggest that renal haemodynamic abnormalities may be important in the initiation of hypertension in the SHR. These renal circulatory abnormalities and the hypertension of the SHR depend, at least in part, on intact converting enzyme activity, yet appear to be independent of abnormalities of total body sodium. At a later age, hypertension seems to develop independently of renal vascular abnormalities.

Austin E. Doyle

Papers

Plasma Norepinephrine Levels in Essential Hypertension

Smoking as a risk factor for cerebral ischaemia.

Australian Therapeutic Trial in Mild Hypertension

Effects of genetic hypertension on diabetic nephropathy in the rat--functional and structural characteristics.

Persistent effects on blood pressure and renal haemodynamics following chronic angiotensin converting enzyme inhibition with perindopril.