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).

Background—The objective of this study was to examine the association of Joint National Committee (JNC-V) blood pressure and National Cholesterol Education Program (NCEP) cholesterol categories with coronary heart disease (CHD) risk, to incorporate them into coronary prediction algorithms, and to compare the discrimination properties of this approach with other noncategorical prediction functions. Methods and Results—This work was designed as a prospective, single-center study in the setting of a community-based cohort. The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up. During the 12 years of follow-up, a total of 383 men and 227 women developed CHD, which was significantly associated with categories of blood pressure, total cholesterol, LDL cholesterol, and HDL cholesterol (all P,.001). Sex-specific prediction equations were formulated to predict CHD risk according to age, diabetes, smoking, JNC-V blood pressure categories, and NCEP total cholesterol and LDL cholesterol categories. The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used. After adjustment for other factors, ’28% of CHD events in men and 29% in women were attributable to blood pressure levels that exceeded high normal ($130/85). The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ($200 mg/dL) was 27% in men and 34% in women. Conclusions—Recommended guidelines of blood pressure, total cholesterol, and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample. A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD. (Circulation. 1998;97:1837-1847.)

/pdf/prediction-of-coronary-heart-disease-using-risk-factor-2poljzi903.pdf

Prediction of Coronary Heart Disease Using Risk Factor Categories

Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68. Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice suggest that these F4/80+ cells are CSF-1 dependent, bone marrow-derived adipose tissue macrophages. Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-alpha expression and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals.

/pdf/obesity-is-associated-with-macrophage-accumulation-in-130af7ivca.pdf

Obesity is associated with macrophage accumulation in adipose tissue

Background Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently. We studied the effect of an angiotensin-converting-enzyme inhibitor, enalapril, on mortality and hospitalization in patients with chronic heart failure and ejection fractions less than or equal to 0.35. Methods Patients receiving conventional treatment for heart failure were randomly assigned to receive either placebo (n = 1284) or enalapril (n = 1285) at doses of 2.5 to 20 mg per day in a double-bind trial. Approximately 90 percent of the patients were in New York Heart Association functional classes II and III. The follow-up averaged 41.4 months. Results There were 510 deaths in the placebo group (39.7 percent), as compared with 452 in the enalapril group (35.2 percent) (reduction in risk, 16 percent; 95 percent confidence interval, 5 to 26 percent; P = 0.0036). Although reductions in mortality were observed in several categories of cardiac deaths, the largest reduction occurred among the deaths attributed to progressive heart failure (251 in the placebo group vs. 209 in the enalapril group; reduction in risk, 22 percent; 95 percent confidence interval, 6 to 35 percent). There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure. Fewer patients died or were hospitalized for worsening heart failure (736 in the placebo group and 613 in the enalapril group; risk reduction, 26 percent; 95 percent confidence interval, 18 to 34 percent; P less than 0.0001). Conclusions The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions.

Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.

Because of new evidence on several diagnostic and therapeutic aspects of hypertension, the present guidelines differ in many respects from the previous ones. Some of the most important differences are listed below: 
1. Epidemiological data on hypertension and BP control in Europe. 
2. Strengthening of the prognostic value of home blood pressure monitoring (HBPM) and of its role for diagnosis and management of hypertension, next to ambulatory blood pressure monitoring (ABPM). 
3. Update of the prognostic significance of night-time BP, white-coat hypertension and masked hypertension. 
4. Re-emphasis on integration of BP, cardiovascular (CV) risk factors, asymptomatic organ damage (OD) and clinical complications for total CV risk assessment. 
5. Update of the prognostic significance of asymptomatic OD, including heart, blood vessels, kidney, eye and brain. 
6. Reconsideration of the risk of overweight and target body mass index (BMI) in hypertension. 
7. Hypertension in young people. 
8. Initiation of antihypertensive treatment. More evidence-based criteria and no drug treatment of high normal BP. 
9. Target BP for treatment. More evidence-based criteria and unified target systolic blood pressure (SBP) (<140 mmHg) in both higher and lower CV risk patients. 
10. Liberal approach to initial monotherapy, without any all-ranking purpose. 
11. Revised schema for priorital two-drug combinations. 
12. New therapeutic algorithms for achieving target BP. 
13. Extended section on therapeutic strategies in special conditions. 
14. Revised recommendations on treatment of hypertension in the elderly. 
15. Drug treatment of octogenarians. 
16. Special attention to resistant hypertension and new treatment approaches. 
17. Increased attention to OD-guided therapy. 
18. New approaches to chronic management of hypertensive disease

/pdf/2013-esh-esc-guidelines-for-the-management-of-arterial-4eubk4p0u3.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)

The relationship between the degree of obesity and the incidence of cardiovascular disease (CVD) was reexamined in the 5209 men and women of the original Framingham cohort. Recent observations of disease occurrence over 26 years indicate that obesity, measured by Metropolitan Relative Weight, was a significant independent predictor of CVD, particularly among women. Multiple logistic regression analyses showed that Metropolitan Relative Weight, or percentage of desirable weight, on initial examination predicted 26-year incidence of coronary disease (both angina and coronary disease other than angina), coronary death and congestive heart failure in men independent of age, cholesterol, systolic blood pressure, cigarettes, left ventricular hypertrophy and glucose intolerance. Relative weight in women was also positively and independently associated with coronary disease, stroke, congestive failure, and coronary and CVD death. These data further show that weight gain after the young adult years conveyed an increased risk of CVD in both sexes that could not be attributed either to the initial weight or the levels of the risk factors that may have resulted from weight gain. Intervention in obesity, in addition to the well established risk factors, appears to be an advisable goal in the primary prevention of CVD.

Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study.

The natural history of congestive heart failure was studied over a 16-year period in 5192 persons initially free of the disease. Over this period, overt evidence of congestive heart failur...

https://www.nejm.org/doi/pdf/10.1056/NEJM197112232852601

The Natural History of Congestive Heart Failure: The Framingham Study

In the Framingham Study 2325 men and 2866 women 30 to 62 years old at entry were followed biennially over 22 years for the development of chronic atrial fibrillation in relation to antecedent cardiovascular disease and risk factors. During surveillance, atrial fibrillation developed in 49 men and 49 women. The incidence rose sharply with age but did not differ significantly between the sexes. Overall, there was a 2.0 per cent chance that the disorder would develop in two decades. Atrial fibrillation usually followed the development of overt cardiovascular disease. Only 18 men and 12 women (31 per cent) had chronic atrial fibrillation in the absence of cardiovascular disease. Cardiac failure and rheumatic heart disease were the most powerful predictive precursors, with relative risks in excess of sixfold. Hypertensive cardiovascular disease was the most common antecedent disease, largely because of its frequency in the general population. Among the risk factors for cardiovascular disease, diabetes and electrocardiographic evidence of left ventricular hypertrophy were related to the occurrence of atrial fibrillation. The development of chronic atrial fibrillation was associated with a doubling of overall mortality and of mortality from cardiovascular disease.

https://www.nejm.org/doi/pdf/10.1056/NEJM198204293061703?listPDF=true

Epidemiologic features of chronic atrial fibrillation: the Framingham study.

Abstract Risk of coronary heart disease over 14 years was examined prospectively in 2,282 men and 2,845 women according to their antecedent cholesterol and lipoprotein status. An increased risk pro...

Serum Cholesterol, Lipoproteins, and the Risk of Coronary Heart Disease: The Framingham Study

In a sixteen year follow-up study in Framingham, it was found that diabetics in general show an increased morbidity and mortality from all cardiovascular causes. Insulin-treated diabetic women showed the greatest relative mortality from coronary heart disease. Diabetics were found to have higher lipid values, more hypertension and more obesity, even prior to diagnosis. When all the associated risk factors, individually or together, were taken into consideration their presence could not entirely explain the increase in cardiovascular morbidity and mortality experienced by the diabetic. An as yet unknown factor appears to be present in diabetics that could be responsible for much of the higher incidence of cardiovascular complications in diabetics.

Patricia M. McNamara

Papers

Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study.

The Natural History of Congestive Heart Failure: The Framingham Study

Epidemiologic features of chronic atrial fibrillation: the Framingham study.

Serum Cholesterol, Lipoproteins, and the Risk of Coronary Heart Disease: The Framingham Study

Morbidity and Mortality in Diabetics In the Framingham Population: Sixteen Year Follow-up Study