Hypertension cardiovascular disease in diabetes Mohsen Eledrisi MD
Hypertension & cardiovascular disease in diabetes Mohsen Eledrisi, MD, FACP, FACE Department of Medicine Hamad Medical Corporation Doha, Qatar www. eledrisi. com
Session objectives • Discuss the diagnosis and management of hypertension in patients with diabetes • Recognize risk factors for CVD in diabetes • Explain strategies to lower the risk of CVD in diabetes • Describe the management of glycemia in patients with DM and established CVD
Case 1 • A 48 -year-old woman with DM 2 for 3 years • Presents for regular follow up • She has no complaints • Blood pressure 155/92 • BMI 31. 4. Exam otherwise is normal. • How would you manage the blood pressure?
Measuring blood pressure • Proper patient preparation: – Sit quiet in a chair for at least 5 minutes – Seated with back supported (not on table/bed or lying) – Feet on floor, legs uncrossed – Ensure patient emptied his/her bladder – No talking (patient and observer) – No smoking, caffeine, and exercise for 30 minutes before measurement ACC/AHA guidelines. J Am Coll Cardiol 2018; 71: e 127
Measuring blood pressure • Proper technique: – Arm should have no clothes – Shirt’s sleeve not to be rolled up (may act as a tourniquet) – Arm is supported (resting on a disk) – Middle of BP cuff at the level of the heart (mid-sternum) – Appropriate cuff size (tight cuff overestimates BP) • For manual devices: the cuff must cover 75– 100% of the arm circumference • For electronic devices: use cuff according to device instructions ACC/AHA guidelines. J Am Coll Cardiol 2018; 71: e 127
Measuring blood pressure • Documentation: – If BP is high, check both arms – If BP is high, perform 2 more readings: • Separate readings by 1 -2 minutes – If there is a difference between arms >10 mm. Hg in repeated measurements, use the arm with the higher BP – If the difference is >20 mm. Hg consider further investigation – Inform patient about readings (verbally & written) International Society of Hypertension 2020; 75: 1334
What if clinic BP is ≥ 140/90? Confirm with out-of-office measurement Home BP Monitoring or Ambulatory BP Monitoring International society of hypertension. Hypertension 2020; 75: 1334 ACC/AHA guidelines. Circulation 2018; 138(17): e 426. NICE 2019 guidelines.
Home BP Monitoring (HBPM)
Home BP Monitoring (HBPM) • Which machine? – Consult www. stridebp. org (endorsed by International Society of HTN & European Society of HTN) – Use automated arm machines – Use of auscultatory machines is generally not useful as patients/family rarely master them International Society of Hypertension 2020; 75: 1334
Home BP Monitoring (HBPM) • Patient education: • Use appropriate cuff size • Use left & right arms - If there’s a difference, use arm with higher reading • Instruct the patient on how to measure BP
Back supported No talking Quiet room Rest for 5 minutes No smoking, coffee, exercise for 30 min Empty bladder Bottom of cuff above elbow Arm bare & supported on table On chair Legs uncrossed Feet on floor
Home BP monitoring: How frequent? • Take 2 readings each time (separated by 1 minute) - Take the average • Twice daily (morning & evening) • At least 4 days (better 7 days) • Discard 1 st day values • Bring all readings • Take average (mean)
Accuracy of other machines Wrist machines Less accuracy Not recommended
Accuracy of other machines Smart phone applications Not accurate Not recommended
Ambulatory BP Monitoring
Ambulatory BP Monitoring (ABPM ) • Not widely available • Expensive • For 24 hours; every 15 -30 minutes • BP values during different times • At least 20 daytime & 7 nighttime values • Average (mean) is provided
Diagnosis of hypertension HBPM Average 135/85 Overall: 130/80 Daytime: 135/85 Nighttime: 120/70 International Society of Hypertension 2020; 75: 1334
How about if home BP monitoring and Ambulatory BP monitoring are not available Then do office BP follow up
Office blood pressure Proper measurement is important ADA: 2 visits International Society of Hypertension: 2 -3 visits over 1 -4 weeks Take mean (average) BP Hypertension if mean BP ≥ 140/90 American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125 International Society of Hypertension 2020; 75: 1334
Back to our case • Office BP: 155/92 • PLAN: – Repeat BP measurement properly – If BP is still high, it should be confirmed – By home BP or ambulatory BP monitoring – If none available, do office BP
Case 1: Plan • Patient willing to do home BP monitoring • Follow up scheduled after 1 week • Mean home BP: 148/88 – This confirms the diagnosis of hypertension • What is the plan?
ADA guidelines: Blood pressure in diabetes • Patients with confirmed BP ≥ 140/90 mm. Hg: – Lifestyle changes AND – Drug therapy If confirmed BP ≥ 140/90: 1 drug + lifestyle changes If confirmed BP ≥ 160/100: 2 drugs + lifestyle changes American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125
Lifestyle management in HTN • DASH diet: – Rich in fruits, vegetables, whole grains, nuts – Low fat dairy products, poultry, fish, vegetable oil – Reduce saturated and trans fat • Reduced dietary sodium • Physical activity • Weight loss (if overweight or obese) • Smoking cessation American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125 ACC/AHA guidelines. Circulation 2018; 138(17): e 426.
What is the drug of choice for HTN in DM?
Drug choice: HTN in DM If albuminuria or coronary artery disease (CAD): - ACEi or ARB If no albuminuria, no CAD: ADA, JNC, ACC guidelines: - ACEi, ARB, D-CCB or Thiazide-like diuretic (any is acceptable) AACE, NICE guidelines: - ACEi or ARB American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125; JNC 8 JAMA. 2014; 311: 507 ACC/AHA guidelines. Circulation. 2018; 138(17): e 426; AACE 2020 guidelines. NICE 2021 guidelines
Case 2 • A 58 -year-old woman with DM 2 and hypertension • Metformin, Sitagliptin, Simvastatin • For hypertension: Lisinopril 20 mg qd • Office BP 152/90, BMI 28. 4 • A 1 c 6. 8, serum creatinine & potassium normal, LDL 2. 4 mmol • How would you approach the blood pressure?
Diabetes & blood pressure • Patients with DM have higher risk of hypertension • Hypertension risk of cardiovascular complications (MI, stroke, PAD) • Hypertension risk of microvascular complications (nephropathy, retinopathy, possibly neuropathy) • Treatment of HTN reduces ASCVD events, heart failure & microvascular complications American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125
What is the target BP for hypertension in DM?
Target BP in DM ADA guidelines: - If ASCVD or 10 -year ASCVD risk ≥ 15%: <130/80 - If 10 -year ASCVD risk <15%: <140/90 ACC/AHA, ISH guidelines: <130/80 NICE guidelines: <140/90 American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125 International Society of Hypertension 2020; 75: 1334 -1357 ACC/AHA guidelines. Circulation 2018; 138(17): e 426; NICE 2021 guidelines
Use home BP monitoring to follow BP American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125
BP targets with home BP monitoring Office BP Home BP <130/80 <140/90 <135/85 ACC/AHA guidelines. Circulation 2018; 138(17): e 426.
Approach to the patient • Is she adherent to lifestyle changes? • Is she adherent to medications? • Was the BP measured properly? • Does she have a home BP machine?
Case 2: plan & follow up • Confirm blood pressure – Proper office measurement – Advise home BP monitoring • Home BP monitoring in our patient: – Mean BP 144/86 – Remember: target is <135/85 (or <130/80)
Case 2: plan • Either add another agent or maximize dose of current medication • In general, each agent will BP by 10/5 mm. Hg • At half the maximum dose = ~ 75% of full effect • Many will add another agent rather than increasing dose to maximum (no evidence to support this)
Case 2: plan • What should be added after ACEi/ARB in DM? • Guidelines recommend: Dihydropyridine-CCB (Amlodipine, Nifedipine) or Thiazide-like diuretic (Indapamide, chlorthalidone) • Combination single pill can improve patient’s adherence
Management of HTN in DM Go to next step if BP is uncontrolled Lifestyle changes & medications Albuminuria or CAD ACEi or ARB Add CCB or Thiazide-like diuretic No albuminuria, No CAD (ACEi or ARB) or CCB or Thiazide-like diuretic Some authorities recommend starting with ACEi or ARB Add CCB or (ACEi or ARB) or Thiazide-like diuretic Add Thiazide-like diuretic or CCB Add Thiazide-like diuretic or (ACEi or ARB) or CCB Add spironolactone Consider referral (can add Beta blocker, alpha blocker, vasodilator, centrally-acting) CAD: coronary artery disease CCB: calcium channel blocker (dihydropyridine type as amlodipine, nifedipine) Thiazide-like: (as indapamide, chlorthalidone). If not available, use hydrochlorothiazide
Anti-hypertensive classes • Angiotensin converting enzyme inhibitors (ACEi): Agent Starting dose (mg) Usual doses used Usual daily (mg) frequency Benazepril 5 or 10 10, 20, 40 1 Captopril 12. 5 or 25 25, 50, 100 2 -3 times Enalapril 2. 5 or 5 5, 10, 20 1 -2 times Lisinopril 5 or 10 10, 20, 40 1 Perindopril 2. 5 or 5 5, 10 1 2. 5 5, 10, 20 1 Ramipril
Anti-hypertensive classes • ARB (Angiotensin receptor blockers): Agent Starting dose (mg) Usual doses used (mg) Usual daily frequency Candesartan 8 or 16 16, 32 1 150, 300 1 Losartan 25 or 50 50, 100 1 -2 Telmisartan 20 or 40 40, 80 1 Valsartan 40 or 80 Irbesartan 80, 160, 320 1 -2
Anti-hypertensive classes • Diuretics: Thiazide (Hydrochlorothiazide) Thiazide-like (Indapamide, Chlorthalidone) Agent Starting dose (mg) Usual doses used (mg) Usual daily frequency Chlorthalidone 12. 5, 25 1 HCTZ 12. 5, 25 1 1. 25, 2. 5 1 (Hydrochlorothiazide) Indapamide
Anti-hypertensive classes • Diuretics: – Minerlaocorticoid receptor antagonists (MRA) Agent Eplerenone Spironolactone Starting dose (mg) Usual doses used (mg) Usual daily frequency 50 50, 100 1 12. 5 25, 50 1
Anti-hypertensive classes • Dihydropyridine calcium channel blockers: Agent Starting dose Usual doses used Usual daily (mg) frequency Amlodipine 2. 5 or 5 5 , 10 1 Felodipine 2. 5 or 5 5, 10, 20 1 Nifedipine extended release 30 30, 60, 90 1 Nifedipine modified release 10 or 20 20, 40, 60 2 times
Anti-hypertensive classes • Non-Dihydropyridine calcium channel blockers: Agent Diltiazem immediate release Diltiazem extended release Verapamil immediate release Verapamil extended release Starting dose Usual doses used Usual daily (mg) frequency 30 or 60 90, 120 3 -4 times 120 or 180, 240, 360 1 40 or 80 80, 120, 160 2 -3 times 120 or 180, 240, 360 1
Anti-hypertensive classes • Beta blockers: Agent Starting dose (mg) Usual doses used Usual daily (mg) frequency Atenolol 25 or 50 50, 100 1 Bisoprolol 2. 5 or 5 5, 10 1 Carvedilol 6. 25 12. 5, 25 2 times Metoprolol 25 or 50 50, 100 2 times Metoprolol extended release 25 or 50 50, 100 1
Anti-hypertensive classes • Alpha-2 agonist, centrally acting: Agent Clonidine Methyldopa Moxonidine Starting dose (mg) Usual doses used (mg) Usual daily frequency 0. 1 or 0. 2 0. 4, 0. 6, 0. 8 2 times 250 500, 1000 2 -3 times 0. 2, 0. 4 1
Anti-hypertensive classes • Vasodilators: Agent Starting dose Usual doses Usual daily (mg) used frequency (mg) Hydralazine 25 or 50 50, 100 2 -3 times Minoxidil 5 10, 20, 40 1 -2 times
Anti-hypertensive classes • Alpha blockers: Agent Starting dose (mg) Usual doses used Usual daily (mg) frequency Doxazosin 1 or 2 2, 4, 8 1 Prazosin 1 or 2 2, 5 2 -3 times Terazosin 1 2, 5, 10 1 -2 times
Case 3 • A 62 -year-old woman with DM 2 and hypertension • Insulin, Metformin, Gliclazide, Sitagliptin, Enalapril, Amlodipine • BP 126/72, BMI 31 • A 1 c 7. 5, LDL 2. 4 mmol, HDL 0. 9 mmol, TG 1. 8 mmol, serum creatinine & potassium normal • How can the CVD risk be lowered • Should the patient be screened for CAD?
Risk factors for CVD Age (men > 45; women >55) Family history of CAD (man <55; woman <65) Hypertension Dyslipidemia Smoking Obesity Physical inactivity Hyperglycemia
DM & Cardiovascular disease • risk of coronary artery disease by 200 -40% • risk of stroke by 80 -220% • Occurrence of acute cardiac events 15 years earlier • short- & long-term mortality after ACS by 200% • Post-MI complications (recurrent ischemia, failure, shock) • It is the killer: 80% of patients die of CVD Mc. Allister DA, et al. Circulation 2018; 138(24): 2774 Peters S, et al. Lancet 2014; 383: 1973
Primary prevention of CVD in DM • Lifestyle (diet, exercise, healthy weight) • Smoking cessation • Blood pressure control • Statins for high-risk patients • Use of aspirin? • Glucose control American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125
Lifestyle changes & CVD 1) Diet: - Mediterranean diet, DASH diet 2) Healthy weight 3) Physical activity 4) Smoking history - Ask all patients - Counselling if smoking - Refer for smoking cessation assistance
Target BP in DM ADA guidelines: - If ASCVD or 10 -year ASCVD risk ≥ 15%: < 130/80 - If 10 -year ASCVD risk <15%: < 140/90 ACC/AHA, ISH guidelines: <130/80 NICE guidelines: <140/90 American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125 International Society of Hypertension 2020; 75: 1334 -1357 ACC/AHA guidelines. Circulation 2018; 138(17): e 426; NICE 2021 guidelines
Use home BP monitoring to follow BP American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125
BP targets with home BP monitoring Office BP Home BP <130/80 <140/90 <135/85 ACC/AHA guidelines. Circulation 2018; 138(17): e 426.
Statins in diabetes Age ≥ 40 years High intensity statin if: 10 -year ASCVD risk ≥ 20% Or Age 50 -70 Or ≥ 2 CV risk factors (HTN, Generally moderate intensity statin smoking, CKD, albuminuria, family history of premature CVD) American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125 ACC/AHA Guidelines. J Am Coll Cardiol 2018 10. 1016/j. jacc. 2018. 11. 003
Aspirin for primary prevention in DM: The evidence JPAD study: No overall benefit Possible benefit in subgroup analysis (age ≥ 65) JPAD 2: (10 year follow up) No benefit POPADAD trial: No benefit JPAD 2 study. Circulation 2017; 135: 659 JPAD study. JAMA 2008; 300: 2134; POPADAD. BMJ 2008; 337: a 1840
ASCEND trial: largest trial of aspirin in DM ASCEND trial: - RCT: 15, 480 patients with DM (age ≥ 40 years) - Mean Follow-up for 7. 4 years - 1 ry outcome: vascular events (MI, stroke or TIA or death from any vascular cause) - 1 ry safety outcome: major bleeding event (intracranial hemorrhage, bleeding in the eye, GI bleeding, or other serious bleeding). ASCEND trial. N Engl J Med 2018; 379: 1529.
ASCEND trial: results • Reduction in vascular events: – RR 0. 88; 95% CI, 0. 79 -0. 97; P=0. 01 – Number needed to treat (NNT) = 91 • Increased major bleeding events: – RR 1. 29; 95% CI, 1. 09 -1. 52; P=0. 003 – Mainly GI bleeding, others (nose, urine) – Number needed to harm (NNH) = 112 “ Benefits were largely counterbalanced by the bleeding hazard” ASCEND trial. N Engl J Med 2018; 379: 1529.
Aspirin for 1 ry prevention of CVD in DM: ADA guidelines Aspirin is generally not recommended May consider in high CVD risk with low bleeding risk: - Age ≥ 50 years with ≥ 1 CVD risk factors (hypertension, smoking, dyslipidemia, CKD/albuminuria, family h/o premature ASCVD) AND not at increased risk of bleeding (elderly, anemia, renal disease) American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125
Aspirin for 1 ry prevention of CVD in DM: Other guidelines Canadian Diabetes Association: - Aspirin is not recommended NICE (UK): - Aspirin is not recommended Diabetes Canada. Can J Diabetes 2018; 42: S 162 NICE guidelines 2020.
DM agents and risk of CVD • High risk patients (age ≥ 60 years + ≥ 2 CV risk factors) 1) Use GLP-1 RA (1 st option): Reduced cardiac events (MACE) Dulaglutide (level A) Liraglutide (level B) 2) Use SGLT-2 i (2 nd option): Reduced hospitalization for heart failure Dapagliflozin or Canagliflozin (level B) Canadian Diabetes Association. Can J Diabetes 2020; 44: 575 American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125
Should high risk patients be screened for CAD? In asymptomatic patients, routine screening for CAD is not recommended as it does not improve outcomes [Evidence A] American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125
When to investigate for CAD? • The presence of any of the following: – Atypical cardiac symptoms (e. g. unexplained dyspnea, chest discomfort) – Signs or symptoms of associated vascular disease such as carotid bruit, TIA, stroke, claudication, or peripheral arterial disease – ECG abnormalities (e. g. Q waves) [Evidence E = Expert opinion] American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125
Case 4 • A 58 -year-old man with type 2 DM, HTN & CKD • Insulin, Metformin, Dapagliflozin, Nifedipine, Hydralazine, Atenolol, rosuvastatin • BP 134/82 • A 1 c 7. 4, serum creatinine 155 µmol (range in the last year is 145 to 160), potassium 3. 8 , UACR 15 (repeated, 22) (normal <3)
Case 4: Assessment • BP control – Target? – Control? – Agree with treatment? • Kidney function – CKD with albuminuria – Calculate e. GFR – e. GFR = 42. CKD stage 3
BP in CKD • Confirm blood pressure – Proper measurement – Recommend home BP monitoring • Target BP: – <130/80 • Are there preferred agents to use? ACC/AHA guidelines. Circulation 2018; 138(17): e 426;
Anti-HTN medications in CKD • Stage 1, 2 CKD with no albuminuria: • ACEI, ARB, CCB, or thiazide • Stage 1 or 2 with albuminuria or stage 3 or >: – ACEI first line – If ACEI not tolerated, use ARB ACC/AHA guidelines. Circulation 2018; 138(17): e 426;
Primary prevention of CVD in DM • Lifestyle (diet, exercise, healthy weight) • Stop smoking • Blood pressure control • Statins for high-risk patients • Need for aspirin? • Glucose control American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125
CASE 6 • • A 62 -year-old man with DM 2 and hypertension Had acute MI 2 years ago with stent Smoker Insulin, Metformin, Aspirin, Clopidogrel, Lisinopril, Atenolol, Indapamide, Atorvastatin • B. P. 124/70, pulse 88/min • A 1 c 7. 4, LDL 2. 6 mmol (100 mg), HDL 0. 9 mmol (34 mg) • What can be done to lower future risk of CVD?
DM medications and CVD ASCVD Heart failure Metformin Potential benefit Neutral Sulfonylurea Neutral - Neutral (Sita, Lina) - risk (Saxagliptin) DPP-4 i GLP-1 RA SGLT-2 i Pioglitazone Insulin - Benefit (Liraglutide, Dulaglutide) - Neutral (Exenatide ER, Lixisenatide) Neutral Empagliflozin: mortality & events Canagliflozin: events Dapagliflozin: neutral Benefit Potential benefit Neutral American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125 risk Neutral
Management of glucose in ASCVD • Use SGLT-2 i or GLP-1 RA: – Empagliflozin (A) – Canagliflozin (B) - Dapagliflozin did not reduce CV events or mortality – Liraglutide (A) or Dulaglutide (A) – Subcutaneous Semaglutide (B) American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125 Canadian Diabetes Association. Can J Diabetes 2020; 44: S 42
Secondary prevention of CVD in DM Lifestyle changes (healthy weight, exercise, stop smoking) Aspirin for life • Clopidogrel if true documented aspirin allergy • Dual antiplatelets (Aspirin + P 2 Y 12 inhibitor): For 1 year after acute coronary syndrome > 1 year in some high-risk patients if low risk of bleeding • Aspirin + low dose rivaroxaban if low bleeding risk American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125 ACP/AHA/ACC guidelines. Ann Intern Med 2012; 157: 735
Secondary prevention of CVD in DM • Beta-Blockers: Prior myocardial infarction with normal LV function - For 3 years (any Beta blocker) ↓ LVEF ( ≤ 40%): (heart failure or prior MI) - Metoprolol succinate, Carvedilol, or Bisoprolol High-intensity Statin ACEI or ARB Influenza vaccine ( mortality & morbidity) American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125 ACP/AHA/ACC guidelines. Ann Intern Med 2012; 157: 735
LDL levels in patients with DM & ASCVD LDL target should be <1. 8 mmol (70 mg) If LDL is ≥ 1. 8 mmol (70 mg) on maximally tolerated statin dose: Consider adding ezetimibe or PCSK 9 inhibitor Ezetimibe may be preferred due to lower cost American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 125
Summary: key points • Confirm high office BP with home or ambulatory BP • Lifestyle changes and medications for confirmed high BP • Assess patients with DM for risk factors for CVD • Primary prevention of CVD in DM: lifestyle changes, BP & glucose control & statins for high risk • Selected glucose-lowering medications have CV benefits
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