Report from the panel members appointed to the Eighth Joint National Committee (JNC 8) 2014 evidence-based guidelines for the management of high blood pressure in adults Paul A. James, MD; Suzanne Oparil, MD; Barry L. Carter, PharmD; William C. Cushman, MD; Cheryl Dennison-Himmelfarb, RN, ANP, PhD; Joel Handler, MD; Daniel T. Lackland, DrPH; Michael L. LeFevre, MD, MSPH; Thomas D. MacKenzie, MD, MSPH; Olugbenga Ogedegbe, MD, MPH, MS; Sidney C. Smith Jr, MD; Laura P. Svetkey, MD, MHS; Sandra J. Taler, MD; Raymond R. Townsend, MD; Jackson T. Wright Jr, MD, PhD; Andrew S. Narva, MD; Eduardo Ortiz, MD, MPH JAMA. doi:10.1001/jama.2013.284427. Published online December 18, 2013.

Questions guiding the JNC8 review This hypertension guideline focuses on 3 questions related to high blood pressure (BP) management. They address thresholds, goals for pharmacologic treatment, and whether particular antihypertensive drugs or drug classes improve important health outcomes compared to others. In adults with hypertension, does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes? In adults with hypertension, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvements in health outcomes? In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? RAAS and angiotensin II are activated in the insulin resistance state, and RAAS inhibition has effects on insulin action and secretion. Indeed, the vasodilation induced by ACE inhibitors could improve the blood circulation in skeletal muscles, thus favoring peripheral insulin action, but also in the pancreas, promoting insulin secretion. Preserving cellular potassium and magnesium pools by blocking the aldosterone effects could also improve both cellular insulin action and insulin secretion. However, besides these classical effects, new mechanisms have been recently suggested. A direct effect of the inhibition of angiotensin and/or of the enhancement of bradykinin on various steps of the insulin cascade signaling has been described as well as an increase in GLUT4 glucose transporters after RAS inhibition. Furthermore, it has been demonstrated that angiotensin II inhibits adipogenic differentiation of human adipocytes and, therefore, it has been hypothesized that RAS blockade may prevent diabetes by promoting the recruitment and differentiation of adipocytes. In conclusion, numerous physiological and biochemical mechanisms could explain the protective effect of RAS inhibition against the development of type 2 diabetes in individuals with arterial hypertension or congestive heart failure. What might be the main mechanism in the overall protection effect of ACEIs or ARBs remains an open question.  The answers to these three questions are reflected in 9 recommendations JAMA. doi:10.1001/jama.2013.284427. Published online December 18, 2013.

Recommendations (1/3) Recommendation 1 Recommendation 2 BP thresholds Goals Recommendation 1 (Strong recommendation) Recommendation 2 Recommendation 3 (Expert opinion) General population ≥60 years SBP ≥150 mm Hg or DBP ≥90 mm Hg SBP <150 mm Hg and DBP <90 mm Hg General population <60 years DBP ≥90 mm Hg DBP <90 mm Hg A total of 4071 individuals, with hypertension or normotensives, and without previous history of diabetes mellitus were investigated between January 2004 and September 2009. A subgroup of 1856 hypertensive patients who had at least one additional cardiovascular risk factor took part in the treatment analysis. To adjust for potential cofounders, a propensity score matched analysis was performed using the logistic regression model. The population was finally divided as follows: 321 patients for ACE inhibitor users and 321 patients for ARB users. The primary end point was the cumulative incidence of new-onset diabetes mellitus. General population <60 years SBP ≥140 mm Hg SBP <140 mm Hg JAMA. doi:10.1001/jama.2013.284427. Published online December 18, 2013.

Recommendations (2/3) Recommendation 4 Recommendation 5 BP thresholds Recommendation 4 (Expert opinion) Recommendation 5 Recommendation 6 (Moderate recommendation) Goals Population with CKD ≥18 years SBP ≥140 mm Hg or DBP ≥90 mm Hg SBP <140 mm Hg and DBP <90 mm Hg CKD: chronic kidney disease Population with diabetes ≥18 years SBP ≥140 mm Hg or DBP ≥90 mm Hg SBP <140 mm Hg and DBP <90 mm Hg A total of 4071 individuals, with hypertension or normotensives, and without previous history of diabetes mellitus were investigated between January 2004 and September 2009. A subgroup of 1856 hypertensive patients who had at least one additional cardiovascular risk factor took part in the treatment analysis. To adjust for potential cofounders, a propensity score matched analysis was performed using the logistic regression model. The population was finally divided as follows: 321 patients for ACE inhibitor users and 321 patients for ARB users. The primary end point was the cumulative incidence of new-onset diabetes mellitus. Initial treatment Thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB) General nonblack population (with diabetes) JAMA. doi:10.1001/jama.2013.284427. Published online December 18, 2013.

Recommendations (3/3) Recommendation 7 Recommendation 8 (Moderate recommendation) Recommendation 8 Recommendation 9 (Expert opinion) Initial treatments General (with diabetes) black population Thiazide-type diuretic, or calcium channel blocker (CCB) Initial or add-on treatments Population with CKD ≥18 years Angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB) Non control strategies A total of 4071 individuals, with hypertension or normotensives, and without previous history of diabetes mellitus were investigated between January 2004 and September 2009. A subgroup of 1856 hypertensive patients who had at least one additional cardiovascular risk factor took part in the treatment analysis. To adjust for potential cofounders, a propensity score matched analysis was performed using the logistic regression model. The population was finally divided as follows: 321 patients for ACE inhibitor users and 321 patients for ARB users. The primary end point was the cumulative incidence of new-onset diabetes mellitus. Goal BP not reached within a month of treatment Increase the dose of the initial drug, or add a second drug (from the list provided) Goal BP not reached with 2 drugs Add and titrate a third drug (from the list provided) Do not use an ACEI and an ARB together in the same patient JAMA. doi:10.1001/jama.2013.284427. Published online December 18, 2013.

Conclusions This JNC8 guideline has not redefined high BP, and considers the 140/90 mm Hg definition from JNC 7 reasonable. It offers clinicians an analysis of what is known and not known about BP treatment thresholds, goals, and drug treatment strategies to achieve those goals. However 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.