Reframe the Paradigm of Hypertension treatment Focus on Diabetes

Reframe the Paradigm of Hypertension treatment Focus on Diabetes Paola Atallah, MD Lecturer of Clinical Medicine SGUMC EDL monthly meeting October 25,2016

Overview Physiopathology of hypertension Classification of blood pressure Epidemiology i of hypertension Consequences of hypertension Guidelines for the management of hypertension Antihypertensive drugs ADA Guidelines

Pathophysiology of hypertension

What is the goal BP?

Classification of Blood Pressure JNC VII Systolic Diastolic Normal < 120 And < 80 Prehypertension 120-139 Or 80-89 Hypertension Stage 1 140-159 Or 90-99 Stage 2 > 160 Or > 100 Highest value (systolic or diastolic) determines Stage

High/ Very High Risk Subjects BP 180systolic and/or 110mmHg diastolic SBP >160 mmhg with low DBP (<70 mmhg) DM / MS / 3 CV risk factors Subclinical organ damages: LVH Carotid artery wall thickening or plaque Increased arterial stiffness creatinine GFR or Cr Cl Microalbuminuria or proteinuria Established CV or renal disease

Most patients have overlapping CV Risk Factors Overall 23% of individuals without CV comorbidities has HTN Of all dyslipidaemics: 48% have hypertension 14% have type 2 diabetes 35% are overweight/obese HTN was found in: 82% of those with CKD 77% of those with DM 74% in those with PAD 73% of those with CHD Dyslipidaemia 71% in those with CHF 62% in those with MetS 70% in those with stroke 52% in those with dyslipidemia Hypertension Type 2 Diabetes Of all type 2 diabetes: 60% have hypertension 60% have hyperlipidemia 90% are overweight/ obese Wong ND et al. Arch Intern Med 2007;167:2394

Hypertension and Diabetes Hypertension is common in type 1 and type 2 diabetes Time course in relation to the duration of diabetes is different In type1: 5% risk at 10y 33%at 20y 70%at 40y In > 3500 newly diagnosed type 2: 39% HTA 50% of them, HTA before the onset of albuminuria Epstein M, Sowers JR. Diabetes mellitus and hypertension. Hypertension 1992; 19:403.

Renal and cardiovascular disease develop in parallel Renal disease CV disease Renal failure ESD Heart failure GFR decline Progression CV events Proteinuria albuminuria Diabetes, HTN ageing Organ damage High risk CHD LVH Diabetes, HTN, ageing

Guidelines :HTA management One pill for all??

Guidelines Acknowledge That Most Patients Need Combination Therapy to Achieve BP Goals JNC 8 Most patients with hypertension will require two or more antihypertensive medications to achieve their BP goals** J When BP is > 20/10 mmhg above goal, consideration should be given to initiating therapy with two drugs 16 ESH 20 NICE Combination treatment should be considered as first choice when there is high CV risk BP is above the hypertension threshold (> 20/10 mmhg), or multiple risk factors, sub clinical organ damage, diabetes, renal or CV disease The use of two or three drugs in combination is often necessary to achieve the target BP control A low dose of a diuretic should be included in this combination The use of two or three drugs in combination is often necessary to achieve the target BP control A low dose of a diuretic should be included din this combination **Chobanian et al. JAMA. 2008;289:2560 2572; Mancia et al. Eur Heart J. 2007;28:1462 1536; http://www.nice.org.uk/ download.aspx?o=cg034fullguideline (accessed January 2010); Ogihara et al. Hypertens Res. 2009;32:3 107.

Target Blood Pressure <140/90 mmhg Multipleanti hypertensive agents may be needed to achieve the Multiple anti hypertensive agents may be needed to achieve the desired target

Achieving Antihypertensive Goals National Kidney Foundation, Am J Kid Dis 39 (Suppl 1): S1 S321

Hypertension in Diabetes (UKPDS) Patients with eve ents (%) 50 40 30 20 10 0 Less tight control (mean BP 154/87 mmhg) Tight control (mean BP 144/82 mmhg) Tight BP control: 24% reduction of events (95% CI 8-38) 0 1 2 3 4 5 6 7 8 9 Years from randomization guidelines.diabetes.ca 1-800-BANTING (226-8464) diabetes.ca Copyright 2013 Canadian Diabetes Association UKPDS Study Group. BMJ 1998; 317:703-13.

Benefits of BP Lowering in DM Meta analysis of 27 randomized trials showed intense BP reduction (6/4.6 mmhg) resulted in: 36% reduction in stroke 27% reduction in total mortality 25% reduction in major cardiovascular events The important factor was blood pressure reduction not the agent used. Arch Intern Med 2005;165:1410-1419

HOT:BP Control Reduces CV Events Diabetes Subgroup 30 P<0.005 MI, stro oke, CV mortality/ 1000 pt-y 25 20 15 10 24.4 18.8 11.9 Goal of therapy: target diastolic BP 90 mm Hg (n=501) 85 mm Hg g( (n=501) 80 mm Hg (n=499) 5 0 Hansson et al. Lancet. 1998;351:1755.

Antihypertensive drugs and diabetes ARB/ACEI may have positive effects on insulin action and plays a role in protecting high risk hypertensive patients from developing diabetes HOPE The development of new diabetes was reduced by 34% (p<0.001) in the Ramipril treated group LIFE Losartan was associated with 25% relative risk reduction in new onset diabetes when compared with ihatenolol l VALUE Valsartan, was associated with 23% RRR in new onset diabetes when compared with amlodipine

Diuretic - Classes Thiazides Hydrochlorothiazide (HCTZ) 12.5 mg or 25mg Outcome benefits not established Hyponatremia & hypokalemia more common in women >12 combinations with HCTZ available Chlorthalidoneh lid 25 mg provide better 24h hr BP control than HCTZ 50 mg Mg for mg twice as potent as HCTZ Outcome data available regarding reduced CV events

Chlorthalidone Reduces Cardiovascular Events

Chlorthalidone Reduces Cardiovascular Events

Diuretic - Classes Loop If only treating hypertension use only in CKD Potassium sparing Combined with thiazide reduces risk sudden death and hypokalemia Do not combine with continuous K + supplements or in renal failure Increased risk hyperkalemia Especially with ACE or ARB combination

Diuretics diabetes, hyperlipidemia? Diuretics can raise glucose & lipid levels short term However, no long term adverse effects in diabetics Fasting glucose increases in older adults regardless antihypertensive drug Diuretics may be safely used in patients with diabetes or hyperlipidemia

Best drug for Diabetic patients? The choice of antihypertensive agents in diabetic patients is based upon their ability to prevent adverse cardiovascular events and to slow progression of renal disease, if present The choice is not based upon retinopathy endpoints since p p y p comparative trials have not demonstrated superiority of one agent over another for retinopathy

ADA 2016 Guidelines HypertensionManagement: Treatment Targets Measure BP at every visit Confirm elevated BP at separate visit Systolic (SBP) targets <140 mm Hg Lower target (<130 mm Hg) may be appropriate in certain individuals * Screening Treatment targets Diastolic (DBP) targets <90 mm Hg Lower target (<130 mm Hg) may be appropriate in certain individuals * * Younger individuals, those with albuminuria, and/or those with hypertension and one or more additional ASCVD risk factor if lower target can be achieved without undue treatment burden American Diabetes Association. Diabetes Care. 2016;39(suppl 1):S1-S106.

ADA 2016 Guidelines Treatment of High Blood Pressure BP>120/80 mm Hg Lifestyle changes Confirmed office BP >140/90 Older adults Pregnant individuals Prompt initiation and timely subsequent titration of pharmacologic therapy in addition to lifestyle changes Treating to <130/70 is not recommended SBP <130 not shown to improve CV outcomes DBP <70 associated with increased mortality Targets of 110 129/65 79 recommended to optimize long term maternal health and minimize impaired fetal growth Pharmacologic therapy Regimen to include ACEI or ARB but not both If either class is not tolerated, substitute for the other If using ACEI, ARB, or diuretic, monitor serum creatinine/egfr i and serum potassium levels l ACEI=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; egfr=estimated glomerular filtration rate; American Diabetes Association. Diabetes Care. 2016;39(suppl 1):S1-S106.

Weight loss DASH style dietary pattern, including: Lifestyle Changes for High Blood Pressure Reduced sodium intake (<2,300 mg/day) Increased potassium intake Increased fruit/vegetable intake (8 10 servings/day) Moderate alcohol intake Increased physical activity ADA 2016 Guidelines DASH=Dietary Approaches to Stop Hypertension American Diabetes Association. Diabetes Care. 2016;39(suppl 1):S1-S106.

Screening Screening and Treatment for Diabetic Kidney Disease ADA 2016 Guidelines Annually measure urinary albumin and egfr in patients with type 1with 5 yr diabetes duration, in all type 2 patients starting at diagnosis, and in all patients with hypertension For individuals with nondialysis dependent diabetic kidney disease: Dietary protein intake should be 0.8 g/kg of body weight per day For individuals on dialysis: Higher levels of protein intake should be considered ACEI or ARB recommended for treatment of nonpregnant individuals with diabetes and modestly elevated urinary albumin excretion (300-299 mg/d) Treatment Strongly recommended d for individuals id with urinary albumin excretion 300 mg/d and/or egfr <60 ml/min/1.73m 2 Periodically monitor serum creatinine and potassium levels when ACEIs, ARBs, or diuretics are used for treatment Monitor urinary albumin-to-creatinine ratio in individuals with albuminuria treated with ACEI or ARB ACEI or ARB not recommended for primary prevention of diabetic kidney disease in individuals with diabetes who have normal BP, urinary albumin-to-creatinine ratio, and egfr ACEI=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; egfr=estimated glomerular filtration rate American Diabetes Association. Diabetes Care. 2016;39(suppl 1):S1-S106.

Management of for Diabetic Kidney Disease ADA 2016 Guidelines egfr is <60 ml/min/1.73m 2 : evaluate and manage potential complications of chronic kidney disease egfr <30 ml/min/1.73m 2 : refer for evaluation for renal replacement treatment Refer to physician experienced in care of kidney disease for uncertainty about cause of kidneydisease disease, difficultmanagementissues issues, rapidlyprogressingdisease progressing disease egfr 45 60 egfr 30 44 egfr <30 Referral to nephrologist if possibility for nondiabetic kidney disease Consider need for dose adjustment of meds Monitor egfr, electrolytes, bicarbonate, calcium, phosphorous, parathyroid hormone, hemoglobin, albumin, weight every 6 months Assure vitamin D sufficiency Consider bone density testing Refer for dietary counseling Monitor egfr every 3 months Monitor electrolytes, bicarbonate, calcium, phosphorous, parathyroid hormone, hemoglobin, albumin, weight every 3 months Consider needfor dose adjustment of meds Refer to a nephrologist egfr=estimated glomerular filtration rate American Diabetes Association. Diabetes Care. 2016;39(suppl 1):S1-S106.

ADA 2016 Guidelines Screening Treatment Children and Adolescents WithType 1 Diabetes: High Blood Pressure Measure BP at every visit Confirm elevated BP at separate visit High normal BP * or hypertension : confirm BP on 3 separate days High normal BP * Lifestyle changes (diet & physical activity) aimed at weight control Initial pharmacologic If target BP not achieved within 3 6 months, therapy: initiate pharmacologic therapy ACEI or ARB (Never in Hypertension combination) Initiate lifestyle changes and pharmacologic therapy Target: Consistently <90th percentile for age, gender, and height * SBP or DBP consistently 90th percentile for age,, and height SBP or DBP consistently 95th percentile for age, gender, and height Provide counseling regarding potential teratogenic effects Not all ACEIs and ARBs are indicated for use in children/adolescents by the U.S. Food and Drug Administration (FDA). Refer to full prescribing information for indications and uses in pediatric populations. American Diabetes Association. Diabetes Care. 2016;39(suppl 1):S1-S106.

ADA 2016 Guidelines Managing ghypertension During Pregnancy BP is lower during a normal pregnancy than in the nonpregnant state Target BP for pregnancy complicated by diabetes Antihypertensive medications Safe medications Methyldopa Labetalol Diltiazem Clonidine Prazosin SBP: 110 129 mm Hg DBP: 65 79 mm Hg Unsafe medications (contraindicated) ACEIs ARBs ACEI=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; DBP=diastolic blood pressure; SBP=systolic blood pressure American Diabetes Association. Diabetes Care. 2016;39(suppl 1):S1-S106.

Conclusions HTA occurs in 75% of patients t with type 2 diabetes is common in type 1 diabetes HTA is a promoter of macro and micro vascular disease There is evidence to link the RAAS with hypertension in yp patients with obesity, metabolic syndrome, and type 2 diabetes

Summary of Pharmacotherapy for Hypertension in Patients with Diabetes Threshold equal or over 140/90 mmhg and Target below 140/90 mmhg Diabetes With Nephropathy, CVD or CV risk factors Without the above ACE Inhibitor or ARB 1. ACE Inhibitor or ARB or 2. Thiazide diuretic or DHP-CCB Combination of 2 first line drugs may be considered as initial therapy if the blood pressure is >20 mmhg systolic or >10 mmhg diastolic above target > 2-drug combinations Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB More than 3 drugs may be needed to reach target values If Creatinine over 150 µmol/l or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control of volume is desired

We are still evolving towards finding an Ideal Antihypertensive