"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

Introduction In 1836, Sir Richard Bright, widely regarded as the founder of the field of nephrology, described the structural cardiac changes on autopsy seen in patients with “shrunk kidneys” who were secretors of albuminous urine (1). This report is perhaps the earliest description of the cardiorenal connection in contemporary literature of what is known today as CKDassociated cardiomyopathy. This connection is driven by shared risk factors, such as diabetes, hypertension, and obesity, as well as maladaptive cardiorenal crosstalk pathways resulting in bidirectional organ failure.

Changing the Trajectory of Heart Failure and Kidney Disease.

Plasma Renin Activity (PRA) Predicts Diuretic Resistance in Acute Heart Failure Patients: An Ancillary Study of the Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE-AHF)

Impact of atrial fibrillation on exercise capacity in diastolic heart failure: a relax trial ancillary study

Several lines of evidence support a central role for thrombin in the molecular and cellular processes following plaque rupture: (1) thrombus formation at sites of vascular injury in vivo is primarily mediated by thrombin through activation of the coagulation cascade and stimulation of platelet aggregation; (2) thrombin is a key mediator of early smooth muscle cell proliferation following arterial injury; (3) thrombin potentiates the proliferative effects of multiple growth factors; and (4) thrombin regulates in_ammatory processes in neutrophils, monocytes, and their respective counterreceptors by endothelium [1]. Prior studies have demonstrated that thrombins effects can be neutralized by direct or indirect inactivation and by inhibition of thrombin production via the intrinsic or extrinsic limbs of the coagulation pathway [1]. Pilot studies [24] in humans with hirudin, a potent, direct, and highly speci~c inhibitor of free and clotbound thrombin, were promising. Favorable trends in 90 minute infarct-related artery patency rates were seen with hirudin compared to heparin [2,4], and clinical events were lower at the highest doses of hirudin [3]. However, all 3 of the initial large phase III clinical trials (HIT-III, TIMI 9A, GUSTO IIa) testing direct thrombin inhibition with hirudin vs. the indirect action of heparin had to be suspended due to higher than expected hemorrhagic complications. An unacceptable rate of bleeding, especially in an intracranial location, was observed. Following reduction in doses of both heparin and hirudin, and institution of additional hemorrhagic safety precautions, the TIMI 9B [5] and GUSTO IIb [6] trials were carried out. The TIMI 9B study evaluated hirudin vs. heparin as adjunctive therapy in 3,002 patients with acute myocardial infarction who also received aspirin and either streptokinase or accelerated dose tPA. There was no signi~cant difference in the primary endpoint of unsatisfactory clinical outcome (death, recurrent nonfatal myocardial infarction, or development of severe congestive heart failure or cardiogenic shock) by 30 days between the heparin-treated patients (11.9%) and the hirudin-treated patients (12.9%). Similarly, there was no difference in the secondary endpoint of death and nonfatal myocardial infarction (see Table 1). Subgroup analyses failed to identify a patient pro~le that bene~tted more from hirudin. Likewise, a multivariate logistic regression analysis that included previously established risk factors for poor prognosis failed to demonstrate that the antithrombin to which the patient was randomized correlated with unsatisfactory outcome or the sum of death and reinfarction by 30 days. Rates of major hemorrhage (heparin 5.3%, hirudin 4.6%) and intracranial hemorrhage (heparin 0.9%, hirudin 0.4%) were also similar for the 2 antithrombins. In GUSTO IIb, 12,142 patients with acute coronary syndromes were randomized to heparin vs. hirudin. Of the 4,131 patients with ST elevation who were treated with aspirin and tPA or streptokinase, there was no signi~cant difference in the composite endpoint of death and non-fatal reinfarction at 30 days (see Table 1). Similarly for the 8,011 patients with ST depression, there was no signi~cant difference in combined mortality and nonfatal reinfarction between the heparinand hirudin-treated patients at 30 days. For the entire cohort of 12,142 patients, however, a small bene~t of borderline statistical signi~cance was seen for the hirudintreated patients (Table 1). Intracranial hemorrhage rates were 0.4% and 0.5% in patients with ST segment elevation for heparin and hirudin patients respectively. In patients without ST segment elevation, the rates were 0.02% for heparin and 0.2% for hirudin. What are possible explanations for this lack of clinical bene~t despite the theoretical advantages of hirudin over heparin? One possibility is that although hirudin, unlike heparin, is active against both clotbound as well as _uid-phase thrombin [7], heparin has Journal of Thrombosis and Thrombolysis 1997;4:321323 © Kluwer Academic Publishers. Boston. Printed in the Netherlands

Reexamination of the Thrombin Hypothesis: What We Have Learned from TIMI 9B and GUSTO IIb.

Abstract 5581: Cardiovascular Outcomes of Women and Men with Acute Coronary Syndromes and Angiographically Confirmed Epicardial Coronary Artery Disease in TRITON-TIMI 38

Eugene Braunwald

Papers

Changing the Trajectory of Heart Failure and Kidney Disease.

Plasma Renin Activity (PRA) Predicts Diuretic Resistance in Acute Heart Failure Patients: An Ancillary Study of the Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE-AHF)

Impact of atrial fibrillation on exercise capacity in diastolic heart failure: a relax trial ancillary study

Reexamination of the Thrombin Hypothesis: What We Have Learned from TIMI 9B and GUSTO IIb.

Abstract 5581: Cardiovascular Outcomes of Women and Men with Acute Coronary Syndromes and Angiographically Confirmed Epicardial Coronary Artery Disease in TRITON-TIMI 38