"The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure" provides a new guideline
for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of
more than 140 mm Hg is a much more important cardiovascular disease
(CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75
mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive
at 55 years of age have a 90% lifetime risk for developing hypertension; (3)
Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80
to 89 mm Hg should be considered as prehypertensive and require health-promoting
lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should
be used in drug treatment for most patients with uncomplicated hypertension,
either alone or combined with drugs from other classes. Certain high-risk
conditions are compelling indications for the initial use of other antihypertensive
drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor
blockers, β-blockers, calcium channel blockers); (5) Most patients with
hypertension will require 2 or more antihypertensive medications to achieve
goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes
or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal
BP, consideration should be given to initiating therapy with 2 agents, 1 of
which usually should be a thiazide-type diuretic; and (7) The most effective
therapy prescribed by the most careful clinician will control hypertension
only if patients are motivated. Motivation improves when patients have positive
experiences with and trust in the clinician. Empathy builds trust and is a
potent motivator. Finally, in presenting these guidelines, the committee recognizes
that the responsible physician's judgment remains paramount.

https://jamanetwork.com/journals/jama/articlepdf/196589/JSC30096.pdf

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

/pdf/cochrane-handbook-for-systematic-reviews-of-interventions-1xbdy6uvru.pdf

Cochrane Handbook for Systematic Reviews of Interventions

Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall; however, it is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations,2,3 cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.4,5 In fact, the lesions of atherosclerosis represent . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199901143400207

Atherosclerosis — An Inflammatory Disease

Context Little is known about lifetime prevalence or age of onset of DSM-IV disorders. Objective To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Participants Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Main Outcome Measures Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Results Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. Conclusions About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.

https://www.ph.ucla.edu/epi/faculty/detels/PH150/Kessler_DSMIV_AGP2009.pdf

Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication

The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

The effects of early indomethacin administration on late scar formation following myocardial infarction.

Insights in cardiovacular physiology derived from muscle mechanics.

When I graduated from New York University's School of Medicine in 1952, drugs available for the management of cardiovascular diseases were few and with the exception of nitroglycerine, which was widely used in the treatment of angina, they were relatively ineffective. Digitalis was given universally for heart failure, along with painful, deep i.m. injections of the diuretic mercuhydrin; to augment the latter's potency, it was sometimes preceded by large doses of oral ammonium chloride and followed by i.v. theophylline. The only anti-arrhythmic drug available was quinidine, which was widely used for the treatment of many tachyarrhythmias; its intrinsic pro-arrhythmic properties were not suspected. Bradycardia and heart block were treated with oral ephedrine, and in emergencies epinephrine was administered subcutaneously. While heparin and warfarin were available, the indications for their use were unclear and they were not prescribed frequently. High doses of salicylates were administered for acute rheumatic fever, a condition which was still quite common, and penicillin was life saving in many patients with streptococcal endocarditis.

Anti-hypertensive drugs, adrenergic receptor blockers, antiplatelet agents (other than salicylates), cholesterol-lowering agents, and oral diuretics had not yet been developed. The renin–angiotensin–aldosterone axis had not been defined and drugs that blocked its activity did not exist. The entire subject of drug therapy of cardiovascular diseases was well covered in a 1 hour lecture, with time to spare.

Since … 

[↵][1]*Corresponding author. Tel: +1 6177328989, Fax: +1 6179750955, Email: ebraunwald{at}partners.org

 [1]: #xref-corresp-1-1

/pdf/cardiovascular-pharmacology-a-look-back-and-a-glimpse-into-21azqyx77r.pdf

Cardiovascular pharmacology: a look back and a glimpse into the future

Vorapaxar is a first-in-class protease-activated receptor-1 antagonist indicated for secondary prevention in stable patients with previous myocardial infarction (MI) or peripheral artery disease and no cerebrovascular disease. Vorapaxar is not recommended for initiation in the acute phase of acute coronary syndromes (ACS) because of an unfavorable balance between bleeding and efficacy when started in that setting. The aim of this analysis was to investigate outcomes in patients who experienced a new ACS while receiving vorapaxar for long-term secondary prevention. Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic ischemic Events-Thrombolysis In Myocardial Infarction 50 was a randomized, double-blind, placebo-controlled trial of vorapaxar (n = 26,449). We evaluated bleeding and ischemic events during the acute care of patients with a new ACS during the trial. During a median follow-up of 30 months, 799 patients (8.9%) randomized to vorapaxar and 913 (10.0%) to placebo had a new ACS event (p = 0.003); 87% and 86%, respectively, were on study therapy at the time of the event. In a landmark analysis through 7 days after ACS, the rates of Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe bleeding were 0.8% versus 0.8% (hazard ratio [HR] 0.99, 95% CI 0.33 to 2.94) and GUSTO moderate/severe bleeding were 2.5% versus 1.6% (HR 1.59, 95% CI 0.78 to 3.24) with vorapaxar versus placebo. The effect of vorapaxar on cardiovascular death, MI, or stroke (2.4% vs 4.4%; HR 0.54, 95% CI 0.31 to 0.93; p = 0.027) was consistent with the overall trial result. In conclusion, in patients who experience a new ACS event while receiving vorapaxar for secondary prevention, continuing therapy was associated with favorable efficacy without excess severe bleeding during the period of acute ACS management.

Eugene Braunwald

Papers

The effects of early indomethacin administration on late scar formation following myocardial infarction.

Insights in cardiovacular physiology derived from muscle mechanics.

Cardiovascular pharmacology: a look back and a glimpse into the future

Outcomes in Stable Patients With Previous Atherothrombotic Events Receiving Vorapaxar Who Experience a New Acute Coronary Event (from TRA2°P-TIMI 50).

Front-loaded accelerated infusions of tissue plasminogen activator: putting a better foot forward.