RR2011-08 DM and CVD outpatient management - Dr Ha

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Prevention & Management of Cardiovascular Complications of Type II Diabetes:

Prevention & Management of Cardiovascular Complications of Type II Diabetes Dat Ha, DO

Outline::

Outline: Introduction Pathophysiology CV risk factors Preventive measures ADA guidelines

Introduction:

Introduction Well established link between DM and CVD (DM is independent risk factor) Coexisting conditions: HTN, dyslipidemia , smoking Cardiovascular disease (CVD) is the major cause of morbidity and mortality for diabetic patients, and the largest contributor to direct and indirect costs of diabetes

Introduction:

Introduction Risk of CVD (MI, stroke, etc), significantly higher (RR 2.4 to 5.0) in diabetic compared to nondiabetic individuals Nurses Health Study, 117,629 RN aged 35-55 years, followed over 20 years Cardiovascular disease (CVD) is the major cause of morbidity and mortality for diabetic patients, and the largest contributor to direct and indirect costs of diabetes

CVD- RELATED MORTALITY :

CVD- RELATED MORTALITY R.W. Nesto , “Correlation Between Cardiovascular disease and diabetes mellitus: Current Concepts.” Am J Med. 2004; 116(5A): 11S-22S

PATHOPHYSIOLOGY DM-CVD:

PATHOPHYSIOLOGY DM-CVD insulin resistance, oxidative stress, and endothelial dysfunction  proinflammatory , prothrombotic state and atherogenesis Increased in sympathetic tone associated with CV dysfunction  HTN, LV dysfunction, cardiac autonomic neuropathy R.W. Nesto , “Correlation Between Cardiovascular disease and diabetes mellitus: Current Concepts.” Am J Med. 2004; 116(5A): 11S-22S

PATHOPHYSIOLOGY:

PATHOPHYSIOLOGY

SMOKING :

SMOKING Surveys found smoking was higher among diabetics than nondiabetics , even after adjusting for age, sex, race, and education Smoking cessation had greater benefit survival (prolongs life by 3-4 yrs) than most other interventions (lipid lowering, BP control, ASA) Diabetes mellitus and cigarette smoking. Findings from the 1989 National Health Interview Survey. Diabetes Care. 1994;17(7):688. Yudkin . “How can we best prolong life? Benefits of coronary risk factor reduction in non-diabetic and diabetic subjects.” BMJ. 1993; 306; 1313-8

SMOKING:

SMOKING

SMOKING:

SMOKING Brief counseling has been shown to be cost-effective & efficacious 1-800-NO-BUTTS (doubles chances of quitting) >10 cig/d: 21mg qd x 6 wk, 14 mg qd x 2 wk, 7mg qd x 2wk <10 cig/d: 14mg qd x 6wk, 7mg qd x 2 wk

HYPERTENSION :

HYPERTENSION Diabetics have imbalance in autonomics; decreased PNS and increased SNS, related to hyperinsulinemia Insulin-mediated SNS may play role in HTN that develops in 50% of pt with Type 2 DM Comorbid HTN & DM are a/w 2-3x increased in heart failure than DM alone It is proposed that hyperinsulinemia slows the rate of protein breakdown, allowing a buildup of tissue mass and potentiating LVH R.W. Nesto , “Correlation Between Cardiovascular disease and diabetes mellitus: Current Concepts.” Am J Med. 2004; 116(5A): 11S-22S

HYPERTENSION:

HYPERTENSION BP screen every visit: goal < 130/80 (C/B) >130/80, consider lifestyle therapy for maximum 3 months Weight loss, exercise, moderate ETOH, DASH diet Medication should include ACEI or ARB Delay progression of nephropathy, reduced CVD outcomes

HYPERTENSION:

reduction in CHD events after lowering BP <140/90 in diabetics ACCORD trial 2010: Lowering SBP < 120 confers greater CV protection than SBP 130-140 in type 2 DM? Intensive group: BP 119/64 vs Standard group: BP 133/70 Primary outcome: nonfatal MI, nonfatal stroke, CVD death Hazard ratio for primary endpoint in intensive group 0.88 (95% CI 0.73-1.06; P=0.20) Only stroke & nonfatal stroke were statistically significantly reduced in intensive group Stroke - Hazard ratio 0.59 (95% CI 0.39-0.89, P=0.01) Nonfatal stroke – hazard ratio 0.63 (95% CI 0.41-0.96, P=0.03) HYPERTENSION “Effects of Intensive Blood Pressure Control in Type 2 Diabetes Mellitus”. NEJM. 2010: 362: 1575-85

HTN - PREGNANCY:

HTN - PREGNANCY BP goal 110/65-129/79 to minimize impaired fetal growth ACEI and ARB contraindicated (fetal damage) Options: Methyldopa Labetalol Diltiazem Clonidine Prazosin

DYSLIPIDEMIA :

DYSLIPIDEMIA Most common in DM II: LDL concentration in DM II is similar to that of non-DM, however they are smaller, denser & more prone to oxidation, thereby increasing risks of CV events  TG &  HDL

FACTORS AFFECTING LIPIDS :

FACTORS AFFECTING LIPIDS Glycemic load Alcohol Hypothyroidism

DYSLIPIDEMIA - SCREENING :

DYSLIPIDEMIA - SCREENING ADA recommendation: fasting lipid profile at least annually in diabetics Low risk lipid profiles may be screened q2 ys HDL > 50 mg/dl, LDL < 100mg/dl, TG < 150 mg/dl

DYSLIPIDEMIA-MANAGEMENT:

DYSLIPIDEMIA-MANAGEMENT Nutrition & Physical activity Reduces LDL by 15-25 mg/dl Reduction of saturated fat, trans fat, cholesterol intake Increases omega-3, viscous fiber, plant sterols Weight loss Address comorbidities (hypothyroid, ETOH, optimize glycemic control)

DYSLIPIDEMIA - PRIORITIES:

DYSLIPIDEMIA - PRIORITIES Treatment of LDL cholesterol is first priority Hypertriglyceridemia may be CVD risk factor in DM TG 200-400: glycemic control, consider Rx TG > 400: consider Tx w/ fibric acid or niacin to reduce risk pancreatitis increased risk of myositis gemfibrozil + statin renal disease

DYSLIPIDEMIA-MANAGEMENT:

DYSLIPIDEMIA-MANAGEMENT LDL goal < 100 mg/ dL (A) Lower risk pts (without CVD and <40 yo ): Statin in addition to lifestyle changes If LDL goal not reached on maximal statin , a 30-40% reduction in LDL from baseline is acceptable (A) HDL > 40 mg/ dL (men), >50 (women), TG <150 mg/ dL (Grade C)

DYSLIPIDEMIA-MANAGEMENT:

DYSLIPIDEMIA-MANAGEMENT Statin should be added to lifestyle changes regardless (!) of baseline lipids for these diabetics With overt CVD Without overt CVD but >40ys & additional risk factors LDL goal < 70 (optional, Grade B)

ANTIPLATELETS :

ANTIPLATELETS Platelets: important role in atherogenesis Coexisting CV Risk factors (HTN, smoking, hyperlipidemia ) in DM increase atherothrombotic risk Diabetics have larger, more reactive platelets Diabetes Mellitus and Cardiovascular Prevention: The Role and the Limitations of Currently Available Antiplatelet Drugs,” International Journal of Vascular Medicine , vol. 2011, Article ID 250518, 5 pages, 2011

ANTIPLATELETS:

ANTIPLATELETS The role of antiplatelets (ASA, clopidogrel) in secondary prevention of CVD (MI, ischemic stroke, UA) is well accepted The role of antiplatelets in primary prevention of CVD, both with & without DM, is more controversial

ASPIRIN AS PRIMARY PREVENTION:

ASPIRIN AS PRIMARY PREVENTION JPAD (Japanese Prevention of Atherosclerosis with aspirin for Diabetes) POPADAD (Prevention of Progression of Arterial Disease and Diabetes) ETDRS (Early Treatment of Diabetic Retinopathy Study) BMD (British Medical Doctors) PHS (Physicians’ Health Study) TPT (Thrombosis Prevention Trial) HOT (Hypertension Optimal Treatment) PPP (Primary Prevention Project) WHS (Women’s Health Study)

RECONCILIATION:

RECONCILIATION Antithrombotic Trialists (ATT) Collaboration – meta-analysis of six trials (95,000 patients, 4000 with DM): ASA reduced risk of vascular events (mostly nonfatal MI) by 12% (RR 0.88, 95% CI 0.82 to 0.94) Meta-analysis, JACC (Journal of American College of Cardiology), 3 additional trials (JPAD, POPADAD, ETDRS): ASA associated with 9% decrease in risk CHD events (nonfatal & fatal MI) (but not statistically significant, RR 0.91, 95% CI 0.79-1.05) Aspirin for primary prevention of cardiovascular events in people with diabetes. J. Am. Coll. Cardiol . 2010, 55; 2878-2886

ADVERSE EFFECTS :

ADVERSE EFFECTS Intracranial bleeding – hemorrhagic stroke 1 in 10,000 people annually Extracranial bleeding – mainly GI 3 in 10,000 people annually Aspirin for primary prevention of cardiovascular events in people with diabetes. J. Am. Coll. Cardiol . 2010, 55; 2878-2886

ADA 2011 & AHA 2010 GUIDELINES:

ADA 2011 & AHA 2010 GUIDELINES ASA (75-162 mg/d) recommended for secondary prevention in diabetics with hx CVD (MI, vascular bypass, angina, stroke/TIA, PVD) – Grade A Consider ASA (75-162 mg/d) as primary prevention in diabetics (type 1 or 2) at increased CV risk (10 year risk > 10%)-Grade C Men > 50 yo Women > 60 yo PLUS >1 RF CVD (smoking, HTN, dyslipidemia , FHx CHD, albuminuria , obesity) For patients with ASA allergy, clopidogrel (75 mg/day) is recommended (Grade B) ASA is CONTRAINDICATED in patients <21 yo (Reyes syndrome)

SPECIAL THANKS :

SPECIAL THANKS Dr. Flattery Drs Haefner & Nelson

References :

References R.W. Nesto , “Correlation Between Cardiovascular disease and diabetes mellitus: Current Concepts.” Am J Med. 2004; 116(5A): 11S-22S American Diabetes Association: Dyslipidemia management in adults with diabetes. Diabetes Care 27 (Supplement 1), 2004 American Diabetes Association: standards of medical care in diabetes 2011. Diabetes Care 34 (Supplement 1), 2011 ADA, AHA, ACCF: Aspirin for primary prevention of cardiovascular events in people with diabetes. J. Am. Coll. Cardiol . 2010, 55; 2878-2886 A. Tufano , E. Cimino , M. N. D. Di Minno , et al., “Diabetes Mellitus and Cardiovascular Prevention: The Role and the Limitations of Currently Available Antiplatelet Drugs,” International Journal of Vascular Medicine , vol. 2011, Article ID 250518, 5 pages, 2011 Yudkin . “How can we best prolong life? Benefits of coronary risk factor reduction in non-diabetic and diabetic subjects.” BMJ. 1993; 306; 1313-8 “Effects of Intensive Blood Pressure Control in Type 2 Diabetes Mellitus”. NEJM. 2010: 362: 1575-85 Uptodate

MKSAP I - Question:

MKSAP I - Question A 60yo man with DM2 and HTN visits to establish care. He reports monitoring his blood pressure and blood glc at home with good results. He had a cholesterol panel checked 5 ys ago at which time he was instructed to exercise, lose weight, and reduce his intake of dietary cholesterol. He has made some lifestyle changes, which he believes have helped his blood pressure and glucose control. His HTN has been treated for 15 ys and his DM for 5 ys . His medication include Lisinopril , Amlodipine , Metformin , ASA.

MKSAP I - Question:

MKSAP I - Question Physical examination: 128/65, HR 76, BMI 26 Lab: TC 215mg/dl, TGL 185mg/ dL , HDL 39mg/dl, LDL 145mg/dl, HbA1c 6.5% Which of the following medications is the best choice for reducing the risk for CVD? A – Coestipol B – Ezetimibe C – Niacin D – Simvastatin

MKSAP I - Question:

MKSAP I - Question Physical examination: 128/65, HR 76, BMI 26 Lab: TC 215mg/dl, TGL 185mg/ dL , HDL 39mg/dl, LDL 145mg/dl, HbA1c 6.5% Which of the following medications is the best choice for reducing the risk for CVD? A – Coestipol B – Ezetimibe C – Niacin D – Simvastatin

MKSAP I – ANSWER  D:

MKSAP I – ANSWER  D The indication to initiate cholesterol-lowering medication as well as the goal level for treatemnt are dependent on the absolute level of LDL and the estimated 10-year risk for a coronary artery disease event. This patient has multiple risk factors for CVD (HTN, DM, HLD)

MKSAP II - Question:

MKSAP II - Question A 62yo man is evaluated for HTN. In home blood pressure measurements over the past 2 weeks his average blood pressure has been 128/90. He has DM2 and had an inferior myocardial infarction 5ys ago (s/p bare metal stent). Current medication: Lisinopril 10mg/d, Metoprolol 50mg bid, ASA, Pravastatin , Glipizide Physical exam: 130/95, HR 56, RR 14, BMI 28, cardiac auscultation reveals an S4 HbA1c 6.8%, urine Alb/ Crea 10mg/g

MKSAP II - Question:

MKSAP II - Question EKG: SR at 60, first degree AV block, Q waves in II, III, aVF , nonspecific T-wave abnormalities Which is the most appropriate treatment for this patient: A – increase Metoprolol B – increase Lisinopril C – add Losartan D – substitute Losartan for Lisinopril E – make no change at this time

MKSAP II - Question:

MKSAP II - Question EKG: SR at 60, first degree AV block, Q waves in II, III, aVF , nonspecific T-wave abnormalities Which is the most appropriate treatment for this patient: A – increase Metoprolol B – increase Lisinopril C – add Losartan D – substitute Losartan for Lisinopril E – make no change at this time

MKSAP II – ANSWER  B:

MKSAP II – ANSWER  B The blood pressure goal is 130/80 in patients with DM. Increasing the dosage of lisinopril is the most appropriate option for this patient with DM, CAD, HTN and persistent elevation of his diastolic blood pressure. In patients with CAD both ACEI and b-blockers have been found to reduce the risk of recurrent cardiovascular events. Lowering the diastolic pressure should be gradual in pts with CAD or >60 and with DM to avoid inducing myocardial ischemia

5 MINUTES::

5 MINUTES: Today: RELATIVE RISK

RR – Relative Risk:

RR – Relative Risk Risk of an event relative to exposure Event can be disease or death Exposure can be to exposure to therapy or environmental exposure

Here’s the 2x2 table again:

Here’s the 2x2 table again interesting outcome Present Absent total Exposed a b a+b Not exposed c d c+d Total a+c b+d a+b+c+d

How to calculate the RR:

How to calculate the RR interesting outcome Present Absent total Exposed a b a+b Not exposed c d c+d Total a+c b+d a+b+c+d [ a/( a+b ) ] / [ c/( c+d ) ] a/( a+b ) c /( c+d )

Example: “July Effect “ :

Example: “July Effect “ Review “July Effect”: Impact of the Academic Year-End Changeover on Patient Outcomes. A Systematic Review John Q. Young , MD, MPP; Sumant R. Ranji , MD; Robert M. Wachter , MD; Connie M. Lee , MD; Brian Niehaus , MD; and Andrew D. Auerbach , MD, MPH

“July Effect” and mortality:

“July Effect” and mortality interesting outcome (mortality) Present Absent (dead) (not dead) total Exposed a (36) b (964) a+b (1000) (July admission) Not exposed c (3) d (997) c+d (1000) (admission out of July) Total a+c b+d a+b+c+d [ a/( a+b ) ] / [ c/( c+d ) ] 36/1000 3/1000 =12

What does the RR mean?:

What does the RR mean? = 1  no difference > 1  more likely to occur in test group < 1  less likely to occur in test group [a/( a+b )] / [c/( c+d )]

RR – remember::

RR – remember: Use in RCT and cohort studies Need group of people with and without exposure Cannot use if case-control study No information about the actual risk

Slide 46:

That’s it. Thanks.

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