CONTROL OF HYPERTENTION IN SPECIAL GROUPS

HYPERTENTION IN PREGNANCY

Etiology & Definition Complicates 10-20% of pregnancies Elevation of BP ≥140 mmHg systolic and/or ≥90 mmHg diastolic, on two occasions at least 6 hours apart.

Categories Chronic Hypertension Gestational Hypertension Preeclampsia Preeclampsia superimposed on Chronic Hypertension

Chronic Hypertension “Preexisting Hypertension” Definition Systolic pressure ≥ 140 mmHg, diastolic pressure ≥90 mmHg, or both. Presents before 20 th week of pregnancy or persists longer then 12 weeks postpartum. Causes Primary = “Essential Hypertension” Secondary = Result of other medical condition (ie: renal disease)

Prenatal Care for Chronic Hypertensives Electrocardiogram should be obtained in women with long-standing hypertension. Baseline laboratory tests Urinalysis, urine culture, and serum creatinine, glucose, and electrolytes Tests will rule out renal disease, and identify comorbidities such as diabetes mellitus. Women with proteinuria on a urine dipstick should have a quantitative test for urine protein.

Treatment for Chronic Hypertension Avoid treatment in women with uncomplicated mild essential HTN as blood pressure may decrease as pregnancy progresses. May taper or discontinue meds for women with blood pressures less than 120/80 in 1 st trimester. Reinstitute or initiate therapy for persistent diastolic pressures >95 mmHg, systolic pressures >150 mmHg, or signs of hypertensive end-organ damage. Medication choices = Oral methyldopa and labetalol.

Preeclampsia Definition = New onset of hypertension and proteinuria after 20 weeks gestation. Systolic blood pressure ≥140 mmHg OR diastolic blood pressure ≥90 mmHg Proteinuria of 0.3 g or greater in a 24-hour urine specimen Preeclampsia before 20 weeks, think MOLAR PREGNANCY! Categories Mild Preeclampsia Severe Preeclampsia Eclampsia Occurrence of generalized convulsion and/or coma in the setting of preeclampsia, with no other neurological condition.

Preeclampsia Severe Preeclampsia must have one of the following: Symptoms of central nervous system dysfunction = Blurred vision, scotomata, altered mental status, severe headache Symptoms of liver capsule distention = Right upper quadrant or epigastric pain Nausea, vomiting Hepatocellular injury = Serum transaminase concentration at least twice normal Systolic blood pressure ≥160 mm Hg or diastolic ≥110 mm Hg on two occasions at least six hours apart Thrombocytopenia = <100,000 platelets per cubic milimeter Proteinuria = 5 or more grams in 24 hours Oliguria = <500 mL in 24 hours Severe fetal growth restriction Pulmonary edema or cyanosis Cerebrovascular accident

Preeclampsia superimposed on Chronic Hypertension Affects 10-25% of patients with chronic HTN Preexisting Hypertension with the following additional signs/symptoms: New onset proteinuria Hypertension and proteinuria beginning prior to 20 weeks of gestation. A sudden increase in blood pressure. Thrombocytopenia. Elevated aminotransferases.

Treatment of Preeclampsia Definitive Treatment = Delivery Major indication for antihypertensive therapy is prevention of stroke. Diastolic pressure ≥ mmHg or systolic pressure ≥160 mmHg Choice of drug therapy: Acute – IV labetalol, IV hydralazine, SR Nifedipine Long-term – Oral methyldopa or labetalol

Gestational Hypertension Mild hypertension without proteinuria or other signs of preeclampsia. Develops in late pregnancy, after 20 weeks gestation. Resolves by 12 weeks postpartum. Can progress onto preeclampsia. Often when hypertension develops <30 weeks gestation. Indications for and choice of antihypertensive therapy are the same as for women with preeclampsia.

Risk Factors for Hypertension in Pregnancy Nulliparity Preeclampsia in a previous pregnancy Age >40 years or <18 years Family history of pregnancy-induced hypertension Chronic hypertension Chronic renal disease Antiphospholipid antibody syndrome or inherited thrombophilia Vascular or connective tissue disease Diabetes mellitus (pregestational and gestational) Multifetal gestation High body mass index Male partner whose previous partner had preeclampsia Hydrops fetalis Unexplained fetal growth restriction

Evaluation of Hypertension in Pregnancy History ID and Complaint HPI (S/S of Preeclampsia) Past Medical Hx, Past Family Hx Past Obstetrical Hx, Past Gyne Hx Social Hx Medications, Allergies Prenatal serology, blood work Assess for Hypertension in Pregnancy risk factors Physical Vitals HEENT = Vision Cardiovascular Respiratory Abdominal = Epigastric pain, RUQ pain Neuromuscular and Extremities = Reflex, Clonus, Edema Fetus = Leopold’s, FM, NST

Evaluation of Hypertension in Pregnancy Laboratory Tests CBC (Hgb, Plts) Renal Function (Cr, UA, Albumin) Liver Function (AST, ALT, ALP, LD) Coagulation (PT, PTT, INR, Fibrinogen) Urine Protein (Dipstick, 24 hour)

Management of Hypertension in Pregnancy Depends on severity of hypertension and gestational age!!!! Observational Management Restricted activity Close Maternal and Fetal Monitoring BP Monitoring S/S of preeclampsia Fetal growth and well being (NST, and U/S) Routine weekly or biweekly blood work

Management of Hypertension in Pregnancy Medical Management Acute Therapy = IV Labetalol, IV Hydralazine, SR Nifedipine Expectant Therapy = Oral Labetalol, Methyldopa, Nifedipine Eclampsia prevention = MgSO4 Contraindicated antihypertensive drugs ACE inhibitors Angiotensin receptor antagonists

Management of Hypertension in Pregnancy Proceed with Delivery Vaginal Delivery VS Cesarean Section Depends on severity of hypertension! May need to administer antenatal corticosteroids depending on gestation! Only cure is DELIVERY!!!

Medical Education & Information – for all Media, all Disciplines, from all over the World Powered by 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) - J Hypertension 2013;31: Definitions and classification of office BP levels (mmHg)* CategorySystolicDiastolic Optimal<120and<80 Normal120–129and/or80–84 High normal130–139and/or85–89 Grade 1 hypertension140–159and/or90–99 Grade 2 hypertension160–179and/or100–109 Grade 3 hypertension≥180and/or≥110 Isolated systolic hypertension≥140and<90 * The blood pressure (BP) category is defined by the highest level of BP, whether systolic or diastolic. Isolated systolic hypertension should be graded 1, 2, or 3 according to systolic BP values in the ranges indicated. Hypertension: SBP >140 mmHg ± DBP >90 mmHg

JNC 8: Graded Recommendations A – Strong evidence B – Moderate evidence C – Weak evidence D – Against E – Expert Opinion N – No recommendation

JNC 8: Drug Treatment Thresholds and Goals Age > 60 yo Systolic: Threshold > 150 mmHg Goal < 150 mmHg LOE: Grade A Diastolic: Threshold > 90 mmHg Goal < 90 mmHg LOE: Grade A

JNC 8: Drug Treatment Thresholds and Goals Age < 60 yo Systolic: Threshold > 140 mmHg Goal < 140 mmHg LOE: Grade E Diastolic: Threshold > 90 mmHg Goal < 90 mmHg LOE: Grade A for ages 40-59; Grade E for ages 18-39

JNC 8: Drug Treatment Thresholds and Goals Age > 18 yo with CKD or DM JNC 7: < 130/80 (MDRD NEJM 1994) Systolic: Threshold > 140 mmHg Goal < 140 mmHg LOE: Grade E Diastolic: Threshold > 90 mmHg Goal < 90 mmHg LOE: Grade E

JNC 8: Initial Drug Choice Nonblack, including DM Thiazide diuretic, CCB, ACEI, ARB LOE: Grade B Black, including DM Thiazide diuretic, CCB LOE: Grade B (Grade C for diabetics)

JNC 8: Initial Drug Choice Age > 18 yo with CKD and HTN (regardless of race or diabetes) Initial (or add-on) therapy should include an ACEI or ARB to improve kidney outcomes LOE: Grade B Blacks w/ or w/o proteinuria ACEI or ARB as initial therapy (LOE: Grade E) No evidence for RAS-blockers > 75 yo Diuretic is an option for initial therapy

JNC 8: Subsequent Management Reassess treatment monthly Avoid ACEI/ARB combination Consider 2-drug initial therapy for Stage 2 HTN (> 160/100) Goal BP not reached with 3 drugs, use drugs from other classes Consider referral to HTN specialist LOE: Grade E

Medical Education & Information – for all Media, all Disciplines, from all over the World Powered by 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) - J Hypertension 2013;31: Blood pressure goals in hypertensive patients SBP, systolic blood pressure; CV, cardiovascular; TIA, transient ischaemic attack; CHD, coronary heart disease; CKD, chronic kidney disease; DBP, diastolic blood pressure. Recommendations SBP goal for “most” Patients at low–moderate CV risk Patients with diabetes Consider with previous stroke or TIA Consider with CHD Consider with diabetic or non-diabetic CKD <140 mmHg SBP goal for elderly Ages <80 years Initial SBP ≥160 mmHg mmHg SBP goal for fit elderly Aged <80 years <140 mmHg SBP goal for elderly >80 years with SBP ≥160 mmHg mmHg DBP goal for “most”<90 mmHg DB goal for patients with diabetes<85 mmHg

Medical Education & Information – for all Media, all Disciplines, from all over the World Powered by 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) - J Hypertension 2013;31: RecommendationsAdditonal considerations Mandatory: initiate drug treatment in patients with SBP ≥160 mmHg Strongly recommended: start drug treatment when SBP ≥140 mmHg SBP goals for patients with diabetes: <140 mmHg DBP goals for patients with diabetes: <85 mmHg All hypertension treatment agents are recommended and may be used in patients with diabetes RAS blockers may be preferred Especially in presence of preoteinuria or microalbuminuria Choice of hypertension treatment must take comorbidities into account Coadministration of RAS blockers not recommended Avoid in patients with diabetes Hypertension treatment for people with diabetes SBP, systolic blood pressure; DBP, diastolic blood pressure; RAS, renin–angiotensin system.

Medical Education & Information – for all Media, all Disciplines, from all over the World Powered by 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) - J Hypertension 2013;31: RecommendationsAdditonal considerations Consider lowering SBP to <140 mmHg Consider SBP <130 mmHg with overt proteinuria Monitor changes in eGFR RAS blockers more effective to reduce albuminuria than other agents Indicated in presence of microalbuminuria or overt proteinuria Combination therapy usually required to reach BP goals Combine RAS blockers with other agents Combination of two RAS blockersNot recommended Aldosterone antagonist not recommended in CKD Especially in combination with a RAS blocker Risk of excessive reduction in renal function, hyperkalemia Hypertension treatment for people with nephropathy SBP, systolic blood pressure; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; RAS, renin–angiotensin system.

Comparison of Recent Guideline Statements JNC 8ESH/ESCAHA/ACCASH/ISH >140/90 Threshold>140/90 < 60 yrEldery SBP >160>140/90 <80 yr for Drug Rx>150/90 >60 yrConsider SBP>140/90>150/90 >80 yr if <80 yr B-blockerNoYesNo First line Rx Initiate Therapy>160/100"Markedly>160/100 w/ 2 drugselevated BP"

Comparison of Recent Guideline Statements JNC 8ESH/ESCAHA/ACCASH/ISH >140/90 Threshold>140/90 < 60 yrEldery SBP >160>140/90 <80 yr for Drug Rx>150/90 >60 yrConsider SBP>140/90>150/90 >80 yr if <80 yr B-blockerNoYesNo First line Rx Initiate Therapy>160/100"Markedly>160/100 w/ 2 drugselevated BP"

Goal BP GroupBP Goal (mm Hg) GeneralDM*CKD** JNC 8:<60 yr: <140/90< 140/90 >60 yr: <150/90 ESH/ESC:< 140/90< 140/85< 140/90 Elderly /90(SBP < 130 if proteinuria) (<80 yr: SBP<140) ASH/ISH< 140/90 >80 yr: <150/90(Consider < 130/80 if proteinuria) AHA/ACC< 140/90 *ADA: < 140/80 or lower **KDIGO: <140/90 w/o albuminuria 30 mg/24hr

Medical Education & Information – for all Media, all Disciplines, from all over the World Powered by 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) - J Hypertension 2013;31: Lifestyle changes for hypertensive patients * Unless contraindicated. BMI, body mass index. Recommendations to reduce BP and/or CV risk factors Salt intakeRestrict 5-6 g/day Moderate alcohol intakeLimit to g/day men, g/day women Increase vegetable, fruit, low-fat dairy intake BMI goal25 kg/m 2 Waist circumference goalMen: <102 cm (40 in.)* Women: <88 cm (34 in.)* Exercise goals≥30 min/day, 5-7 days/week (moderate, dynamic exercise) Quit smoking

Hypertension in the Elderly Fastest growing segment of the population Prevalence of hypertension is very high Several issues make managing HTN unique: Often present with isolated systolic HTN More likely to present with comorbidities Many clinical trials in HTN have excluded these patients (particularly for those 80 years and older) Elderly are more susceptible to certain adverse effects (orthostatic hypotension)

Hypertension in the Elderly HYVET demonstrated that treatment of HTN to goal BP less than 150/80 mm Hg in patients >80 years old was safe and effective But…what about a lower BP goal? And…what about the patients age 60-80?

Hypertension in the Elderly Two “treat-to-target” trials in this age group Japanese Trial to Assess Optimal SBP (JATOS) 4416 patients aged (average age of 74) Randomized to SBP<140 vs. SBP Achieved BP of 136/75 vs. 146/78 No difference in CV events or renal failure (p=0.99) VALISH trial 3079 patients aged (average age of 76) Randomized to SBP<140 or SBP No significant reductions in stroke, CV events, or renal failure Overall event rates were lower than anticipated in both of these studies JATOS Study Group. Hypertens Res 2008;31: Ogihara T et al. Hypertension 2010;56:

Hypertension in the Elderly The opposing arguments: The Japanese trials had low event rates and may not represent the risks in other populations Data from other studies suggests a goal SBP closer to 140mm Hg may be more appropriate for ages Methodology may have prevented JNC-8 panel from considering the results in their analysis The “Speed Limit” effect Wright JT Jr et al. Ann Intern Med 2014;160:

Hypertension in Diabetics Action to Control CV Risk in Diabetes (ACCORD) Randomized, double-blind trial Included patients with T2DM and high CV risk Randomized to SBP<120 or SBP<140 Primary outcome of CV death, MI, or stroke Results Mean SBP of 119 mm Hg vs. 133 mm Hg No significant difference in primary outcome (HR=0.88, p=0.2) Incidence of stroke was lower with intensive treatment (HR 0.59, p=0.01) Significant increase in serious adverse events The ACCORD Study Group. N Engl J Med 2010;362:

Comparisons to Other Guidelines BP GoalJNC-7JNC-8ASH/ISHESC/ES H CHEP Age < 60<140/90 Age <140/90<150/90<140/90 Age 80+<140/90<150/90 Diabetes<130/80<140/90 <140/85<130/80 CKD<130/80<140/90 <130/90<140/90 Adapted from Salvo M et al. Ann Pharmacother 2014;48:

Comparisons to Other Guidelines JNC-7JNC-8ASH/ISHESC/ES H CHEP Non- black (no DM or CKD) ThiazideThiazide, ACEI, ARB, CCB <60:ACE I,ARB >60:CCB, thiazide Thiazide, ACEI, ARB, CCB, BB Thiazide, ACEI, ARB (BB if <60) Black (no DM or CKD) ThiazideThiazide, CCB Thiazide, ACEI, ARB, CCB, BB Thiazide, ARB (BB if <60) DiabetesACEI, ARB, CCB, BB, thiazide CCB, thiazide ACEI, ARB, CCB, thiazide ACEI, ARB ACEI, ARB, CCB, thiazide CKDACEI, ARB Adapted from Salvo M et al. Ann Pharmacother 2014;48:

Hypertension and The Kidney Update: Clinical Trials Paul J. Scheel, Jr., M.D. Director, Division of Nephrology The Johns Hopkins University School of Medicine

Diabetes 45% Other Glomerulonephritis Hypertension Primary Diagnosis in Patients With Kidney Disease Patient Primary Diagnosis USRDS 2010Annual Data Report. The data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. government. Available at: Accessed 3/28/05.

Combination Therapy for BP Control: Rule Rather Than Exception 43 Number of BP Medications ALLHAT IDNT RENAAL UKPDS ABCD MDRD HOT AASK Trial/Systolic Blood Pressure Achieved Adapted from Bakris et al. Am J Kidney Dis. 2000;36: mm Hg 141 mm Hg 144 mm Hg 138 mm Hg 128 mm Hg 132 mm Hg

Lower BP Slows Decline in GFR MAP (mmHg) GFR (mL/min/year) 130/85140/90 Untreated HTN Bakris GL et al. Am J Kidney Dis. 2000; 36(3):

Hypertension and The Kidney Significant Publications 2013 The Coral Trial Symplicity HTN I, II, III Study JNC VIII

Atherosclerotic Narrowing of Proximal Renal Artery

CORAL Trial 947 Patients Radomized Medical Therapy Medical Therapy plus Stent Systolic HTN despite 2 or more drugs or CKD Endpoints: Death,MI, Stroke, CHF, Progressive CKD or Need for Dialysis

Kaplan–Meier Curves for the Primary Outcome. Cooper CJ et al. N Engl J Med 2014;370:13-22.

Cooper et al.NEJM. 2014;370(1):13-22

The Coral Trial Results: - No difference in composite end point between the treatment groups. -No difference in individual components of primary endpoint between the treatment groups. -Modest difference in control of systolic BP in patients treated with stents ( -2.3 mm Hg, P= 0.03)

Percutaneous Renal Denervation Symplicity HTN Study Symplicity I, II, III HTN study designed to study efficacy of radiofrequency ablation of renal artery in patients with resistant HTN

Renal Denervation Symplicity

Renal Artery Denervation

Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study -Open- Label Study of 153 patients with resistant HTN -Eligible Patients: BP > 160 mm Hg on 3 or more anti-hypertensives at “optimum dose” -End Point: Safety and Changes in BP over time. ww.thelancet.com Published online November 7, 2013

Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study ww.thelancet.com Published online November 7, 2013

Renal Sympathetic Denervation for Treatment of Drug- Resistant Hypertension: One Year Results From the Symplicity HTN-2 Randomized Controlled Trial -RCT of Medical Therapy vs Renal Denervation with Cross Over -106 Patients with > Drug Hypertension Randomized -Patients Randomized To Medical Therapy were Crossed Over to Renal Denervation at 6 months. -Patients Followed for 12 months -Primary Endpoint = Control of BP Esler et al. Circulation 2012; 18 (25):

Renal Sympathetic Denervation for Treatment of Drug- Resistant Hypertension: One Year Results From the Symplicity HTN-2 Randomized Controlled Trial Esler et al. Circulation 2012; 18 (25):

Symplicity 3 HTN Trial -535 patients with resistant HTN in 87 US medical centers -Intervention: Radiofrequency ablation vs sham control. -Radomization: 2/3 intervention, 1/3 Sham -Endpoints: safety and efficacy at 6 months -Results: Not published. Press release. Study failed to meet efficacy endpoint at 6 months.

2014 Evidence-Based Guidelines for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eight Joint National Committee ( JNC 8) Three Questions Answered: 1) In adults with HTN, does initiating antihypertensive pharmacologic therapy at specific thresholds improve health outcomes ? 2) In adults with HTN, does treatment with antihypertensive pharmacologic therapy to a specific BP goal lead to improvements in health outcomes ? 3) In adults with HTN, do various antihypertensive drug or drug classes differ in comparative benefits and harms on specific health outcomes ? James et al. JAMA published online December 18, 2013

2014 Evidence-Based Guidelines for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eight Joint National Committee ( JNC 8) Evidence Review: 1) Mortality, CVD-related mortality,CKD-related mortality 2) MI, CHF, hospitalization for CHF or CVA 3) Need for coronary revascularizaton, PTA or stent placement (coronary, carotid,renal or lower extremities) 4) ESRD, or doubling of serum creatinine or 50% reduction in measured GFR 5) Included only RCT James et al. JAMA published online December 18, 2013

2014 Evidence-Based Guidelines for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eight Joint National Committee ( JNC 8) James et al. JAMA published online December 18, 2013

Conclusions -PTA and endovascular stenting of the renal artery for atherosclerotic disease should not be routine practice -Renal artery denervation for resistant hypertension has shown initial promise and we will have to await publication of Simplicity 3 to determine its place in management of severe hypertension -JNC 8 has raised goal BP for most patients with HTN. Jury is still out for patients with CKD or CKD plus proteinuria