Management of HTN in diabetic patient Fatemeh saffarian Assisstant professor of cardiology at qazvin university of medicine

HTN & DM: HTN affecting 60-70% of patients with DM. in type 2 diabetes,HTN is often present as part of the metabolic syn while in type 1,HTN may reflect the onset of diabetic nephropathy. HTN increased risk of both macrovascular & microvascular complication. People with DM & HTN have twice the risk of CVE as non-diabetic people with HTN. masked hypertension is not infrequent, so that monitoring 24-h ambulatory BP in apparently normotensive patients with diabetes,may be a useful diagnostic procedure.

Target level of BP in DM ? Which drugs prefered ? Threshold of initiation of therapy?

Hypertension Guidelines

Case A 58 year old African-American woman with diabetes and dyslipidemia has a BP of 158/94 confirmed on several office visits. Other than obesity, the exam is normal. Labs show normal renal function, well-controlled lipids on atorvastatin and well-controlled diabetes on metformin. Urine micro- albumin is mildly elevated.

Case Question 1 What goal BP is most appropriate for this patient? 1.<150/90 mmHg 2.<130/80 mmHg 3.<140/90 mmHg 4.<140/80 mmHg 5.<140/85 mmHg

Case Question 2 What is the drug of choice to start? 1.HCTZ 2.Norvasc 3.Lisinopril 4.Losartan 5.Combination therapy

Classification of BP – JNC 7 Category Systolic (mmHg) Diastolic (mmHg) Normal< 120and< 80 Pre-HTN or80-89 Hypertension Stage I or90-99 Stage II> 160or> 100

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

Definitions of hypertension by office and out-of-office blood pressure levels: Office : ≥ 140 and/ or ≥ 90 Ambulatory: Daytime (or awake): ≥135 and/or ≥85 Nighttime (or asleep): ≥120 and/or ≥70 24-h: ≥130 and/or ≥80

BP must be remeasured at least 3 times over a period of at least 4 weaks. Except: BP>180/110 or symptomatic or end organ damage

JNC Evidence-Based Guidelines for the Management of High Blood Pressure in Adults –JAMA. 2014;311(5): –December 18, 2013

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 Diastolic: Threshold > 90 mmHg Goal < 90 mmHg –LOE: Grade A for age 30-59; Grade E for ages For patients who can tolerate without asdverse symptom,can target as SBP<130 and DBP<80

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 Diastolic: Threshold > 90 mmHg Goal < 90 mmHg

For patients who can tolerate without asdverse symptom,can target as SBP<130 and DBP<80 For pts with SBP of or DBP of mmHg should initiate lifestyle modification alone,for a maximum of 3 months,if after these,BP not reduced,drug therapy initiated.

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

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

Recent HTN Guideline Statements 2013 ESH/ESC Guidelines for the management of arterial hypertension. J Hypertnsion 2013;31: An Effective Approach to High Blood Pressure Control: A Science Advisory From the AHA, ACC, and CDC. Hypertension online November 15, Clinical Practice Guidelines for the Management of HTN in the Community A Statements by the ASH/ISH. J Hypertension 2014;32:3-15

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

BP goal in the elderly

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 BP <130/90 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 CKDEspecially 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.

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 Canadian D.A:<130/80

Drug therapy of HTN in diabetes ACEI: prefered in most guidelines Favorable effects on glucose metabolism & neghropathy & CVD outcomes. In patient with H.F& post MI ACEI was superior to ARB (OPTIMAL & ELITE II trials) ARB: Similar level of recommendation in guidelines. Prefered in pts with LVH

Drug therapy of HTN in diabetes Dihydropyridine CCB : (amlodipine) Shown superiority to HCT when added to ACEI Bet a blockeres: Masking hypoglycemia symptoms Adverse effects on glucose & lipid metabolism Carvedilol prefered May be in IHD patient but no first line.

Drug therapy of HTN in diabetes Thiazide diuretics: Advers glycemic & triglyceridemic effect ALHHAT trial:compared with lisinopril & amlodipine were similar CVE effect on diabetic patients. In USA,chlorthalidone prefered(longer duration of action,more potent,

Beta-blocker / Diuretic Combination Despite trial evidence of outcome reduction, the BB / diuretic combination favours development of diabetes and should thus be avoided, unless required for other reasons,

ACEI / ARB Combination An ACEI / ARB combination presents a dubious potentiation of benefits with a consistent increase of serious side effects Specific benefits in nephropathic patients with proteinuria (because of a superior antiproteinuric effect) expect confirmation in event based trials

ACEI / CA Combination Tested or widely used combination therapy in Syst-Eur / Syst-China / HOT / ASCOT / INVEST / ACCOMPLISH Greater CV protection than placebo in Syst-Eur / Syst-China Equal (INVEST) or greater (ASCOT) CV protection than D/BB Greater CV protection than ACEI/D in ACCOMPLISH

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

Most guidelines have raised the office BP treatment threshold in DM to 140/90mmHg,except : 2013 ESH/ESC recommended 140/85 if proteinuria;130/ ADA which recommended 140/80mmHg &2013 canadian guidelines that recommended 130/80mmHg

Treatment of risk factors associated with hypertension *It is recommended to use statin in moderate to high CV risk :>40 Y or 100 (target:LDL 50,TG<150) in DM aspirin(75-162mg/day) recommended if man>50 y & woman >60 y In hypertensive patients with DM, a HbA1c target of <7.0%

Thank you for your attention