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Dr. Palmer disclosed no relevant financial relationships with any commercial interests.
Elissa J. Palmer, MD, FAAFP Professor and Chair Department of Family and Community Medicine University of Nevada School of Medicine
Complete management of our patients with cardiometabolic risk includes preventing, and if necessary, treating the myriad of comorbidities and complications associated with the components of cardiometabolic syndrome.
Review current recommendations for antiplatelet therapy, eye care, foot care, vitamin D, and hormones for patients with cardiometabolic risk Outline the evidence for the clinical practice recommendations Assess your clinical practice activities and set up future goals to improve outcomes for patients with cardiometabolic risk
POINTS
Janine
Janine is your 41-year-old, married Caucasian patient who comes in today to discuss labs you ordered after she had a prior first HbA1c of 7.0%. Janine is a nonsmoker. BP = 140/68 mm Hg; P = 68 Reg (no hx arrhythmias); Wt = 185 lbs
TC LDL HDL HbA1C Urine Microalbumin
<60
0 1 4 4 (140/68)
60-74.9 20 >75 41 DM years <5 5-9.9 >10 HbA1c <7 % 7%-7.9% >8% 0 2 6 0 2 5
0 6 10 6 (5.57)
7.5%
40 mcg/min
0 2
Yes
0 1 1 (40)
http://www.dtu.ox.ac.uk/index.php?main doc=/riskengine
30 mcg/min
With her UKPDS score of 13 points, indicating a 10-year risk <15%, and her diagnosis of DM type 2, should you recommended that Janine take one aspirin 81 mg a day?
1. Yes 2. No
University of Oxford. Diabetes Trials Unit. http://www.dtu.ox.ac.uk/index.php?maindoc=/riskengine. Accessed July 23, 2012.
Secondary prevention of CVD (macrovascular disease) Acute MI Occlusive stroke Transient ischemic attack Stable angina Coronary artery bypass surgery In acute ischemic syndromes Acute MI Unstable angina In acute occlusive stroke or a recurrent stroke Primary prevention of a first CVD event Individuals at moderate to high risk
MI = myocardial infarction; CVD = cardiovascular disease. Hennekens CH, et al. Circulation. 1997;96:2751.
No
DM + Low CVD 10-Year Risk (Evidence Level C)
DM + Major Risk Factor 10-Year Risk (Evidence Level C) If >10%: Men >50 Years Women >60 Years 75 to 162 mg/day DM + CVD Secondary Prevention 75-162 mg/day (Evidence Level A)
Yes
Maybe
Clinical Judgment DM + 10-Year Risk (Evidence Level E)
If 5%-10% and other risk factors: Men <50 Years Women <60 Years
Use in DM
DM + CVD: 75-162 mg/day (Evidence Level A)
Comparison to
thienopyridine1,2
Aspirin preferred (Evidence grade 2B) for benefit to risk and cost Slightly > efficacy, so thienopyridine if no cost issue
186,425 individuals with new prescription for low-dose aspirin (300 mg) 186,425 propensity-matched controls, identified January 2003 to December 2008 Hospitalization for major GI bleeding or cerebral hemorrhage compared for aspirin users and non-users Followed 5.7 years
CONCLUSION
Overall incidence of hemorrhagic events Significantly higher for aspirin users than for those without aspirin use
(5.58 vs 3.6 per 1000 person-years; IRR 1.55)
Cessation of aspirin high risk? continue3 ACE inhibitors no issues4 NSAIDs problematic5
ACE = angiotensin-converting-enzyme; NSAIDs = nonsteroidal anti-inflammatory drugs. 1. A randomised, blinded, trial of clopidogrel versus aspirin (CAPRIE). Lancet. 1996;348:1329-1339. 2. De Berardis G, et al. JAMA. 2012;307(21):2286-2294. 3. Hennekens C, et al. Benefits and Risks of Aspirin. Up To Date. April 2012. 4. Teo KK, et al. Lancet. 2002;360:1037-1043. 5. Capone ML, et al. J Am Coll Cardiol. 2005; 45:1295-1301.
Diabetes correlated independently with an increased risk of major bleeding, regardless of aspirin use (IRR 1.36)
RESISTANCE Occurrence of cardiovascular events despite aspirin at recommended doses Lack of evidence to support clinical relevance of aspirin "resistance" in the CVD events that occur
Antithrombotic Trialists' Collaboration1 75 to 325 mg/day Post-hoc subset from CHARISMA trial2 Efficacy same comparing doses of 75 to 150 mg/day (lowdose) and 160 to 325 mg/day (medium (medium-dose) dose) United States Food and Drug Administration 75 to 325 mg/day American College of Cardiology/American Heart Association3
75 to 162 mg/day
Stevenson DD. Immunol Allergy Clin North Am. 2004;24:491-505. Gollapudi RR, et al. JAMA. 2004;292:3017-3023.
Enteric coated
Lack of protection against end point of GI bleeding1 Crush or chew in acute vascular events
1. Kelly JP, et al. Lancet. 1996; 348:1413-1416. 2. Cox D, et al. Stroke. 2006; 37:2153-2158.
Study
Physicians Health Study (PHS) British Doctors Trial (BDT) Thrombosis Prevention Trial (TPT) Primary Prevention Project (PPP) Hypertension Optimal Treatment Trial (HOT) Women's Health Study (WHS) Aspirin for Asymptomatic Atherosclerosis trial (AAAT) Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Prevention of Progression of Arterial Disease and Diabetes (POPADAD)
Aspirin Dose
325 mg qod 500 mg qd 75 mg + warfarin at INR 1.5 Enteric 100 mg qd 75 mg qd 100 mg qd x 10 years 100 mg qd
Reference
N Engl J Med. 1988;318:262 Br Med J (Clin Res Ed). 1988; 296:313 Lancet. 1998; 351:233. Lancet. 2001; 357:89 Lancet. 1998; 351:1755 N Engl J Med. 2005;352:1293 JAMA. 2010;303:841 JAMA. 2008;300:2134. BMJ. 2008;337:a1840
2009 meta-analysis
22 trials of primary and secondary prevention About 135,000 patients Conclusion: No difference in the response to aspirin between men and women
Antithrombotic Trialists' Collaboration. Lancet. 2009;373:1849-1860. Antithrombotic Trialists' Collaboration. BMJ. 2002; 324:71-86.
Underutilized in
Patients with prior occlusive vascular diseases Acute MI Improving Unstable angina in hospital Outpatients with CVD Outpatients with DM
In discussing with Janine initial recommendations for care related to her DM, she should have an initial dilated and comprehensive eye examination upon diagnosis (Evidence Level B). For prevention of diabetic retinopathy, optimal control of which of the following should occur? 1. Weight 2. Hypertension 3. Hyperglycemia 4. Severe hypoglycemic events 5. Both 2 and 3
Few symptoms
Spots of flashes of light Examination important
Glaucoma and cataracts earlier and more frequent Patient concern - blindness
UKPDS study
Glucose control ACCORD trial: subgroup analysis Glucose control FIELD study: subgroup analysis Fenofibrate DCCT BP control
ACCORD = Action to Control Cardiovascular Risk in Diabetes; FIELD = Fenofibrate Intervention and Event Lowering in Diabetes; DCCT = Diabetes Control and Complications Trial. UKPDS. BMJ. 1998;317:708-713. Estacio RO, et al. Diabetes Care. 2000;23 (Suppl 2):B54-B64. ACCORD. N Engl J Med. 2008;358:2545-2559. DCCT. N Engl J Med. 1993;329:977-986.
Female
34.0%
19.7%
Sudden monocular loss of vision in a patient with diabetic retinopathy is most commonly due to: 1. 1 2. 3. 4. 5. Acute glaucoma. A l Vertebrobasilar stroke. Vitreous hemorrhage. Central retinal vein occlusion. Episcleritis.
Duration of DM
Type 1 patients:
25% rate of retinopathy after 5 years 80% at 15 years
Type 2 patients:
Around A d 21% 21%, retinopathy ti th at t diagnosis di i
Type of DM
Screen
Type 1
Within 3-5 years of diagnosis for > age 10 years Annually (can consider less frequent, Level E)
Type 2
At time of diagnosis Annually (can consider less frequent, Level E)
At 1 year
Dilated indirect ophthalmoscopy with fundus photography More frequent screenings for all categories
Janines father has type 2 DM with neuropathy. She would like to know what risk factors she could modify to prevent the development of neuropathy. Of the following, which is the biggest risk factor for developing diabetic neuropathy?
Recommendation
Type
Method 10 g monofilament PLUS one: 128 Hz tuning fork Pinprick sensation Ankle reflexes Vibration perception All patients with DM Multidisciplinary Foot care specialist Consider ankle-brachial index Older than 50 years of age Younger than 50 years of age with risk factors
Evidence
Inspection Pulses Annual Examination Loss sensation Self care, shoes High risk/ulcers Smokers, high-risk Sensation loss Claudication Peripheral pulses
Education
B B B
1. 2. 3. 4. 5.
Coronary artery disease Retinopathy Smoking Uncontrolled high blood sugars over time Uncontrolled high BP over time
Referral
Screen PAD
PAD = peripheral arterial disease. American Diabetes Association. Diabetes Care. 2012:35(Suppl 1). American Diabetes Association. Diabetes Care 2008;26:3333-3341.
Janine asks why the nurse always has her father remove his shoes and socks before you see him. You explain that multiple research studies have demonstrated that the a socks off examination can reduce amputation rates by:
Optimal footwear
Group 0 1
Description No evidence of neuropathy Neuropathy present but no evidence of foot deformity or peripheral vascular disease Neuropathy with evidence of deformity or peripheral vascular disease History of foot ulceration or lower extremity amputation
2 3
18.8% 55.8%
3.1% 20.9%
Janines father, a diabetic with poor control and diagnosed neuropathy, comes in complaining of a sensation of burning in his feet. Which one of the following has the closest correlation with amputations of f the h lower l extremity? ?
1. 2. 3. 4. 5. Pins and needles sensation on feet Loss of ankle reflex Burning sensation on feet Inability to feel pressure with monofilament test Pale and blotchy skin on lower ankles and feet
Device 10-gram (5.07 Semmes-Weinstein) nylon filament standardized to deliver a 10 gram force Use for <100 applications per 24 hours then rest for 24 hours (filament fatigue lessens force) If feel 10 gram force risk ulcer development Prevalenceinsensatefeet: 30%>40years 50% are asymptomatic for 50%>60years
neuropathic symptoms
Rith-Najarian SJ, et al. J Family Practice. 2000;49(11 Suppl):S30-S39. Rith-Najarian SJ, et al. Diabetes Care. 1992;15(10):1386-1389.
Test characteristics Negative predictive value = 90% - 98% Positive predictive value = 18% - 36% Prospective Observational Study 80% of ulcers and 100% of amputations occur in insensate feet Superior predictive value compared to other test modalities
Rith-Najarian SJ, et al. J Family Practice. 2000;49(11 Suppl):S30-S39. Rith-Najarian SJ, et al. Diabetes Care. 1992;15(10):1386-1389.
Tuning Fork (128 Hz) Testing at each hallux Can use in conjunction with monofilament Inexpensive Avoid calluses Document as (+) or (-)
Biosthesiometer Quantitatively assesses vibration sense Can use in conjunction with monofilament Expensive Electrical tuning fork
American Diabetes Association. Diabetes Care. 2012:35(Suppl 1). Miranda-Palma B, et al. Diabetes Res Clin Pract. 2005;70(1):8-12.
Which one of the following is NOT suggestive of autonomic neuropathy? 1. 1 2. 3. 4. 5. Dizziness Third nerve palsy Resting tachycardia Exercise intolerance Constipation
Glucose
Good control and minimize fluctuations
Class
Evidence
Medication Carbamazepine
Dosage 200-400 mg 3 x day 300-1200 mg 3 x day 100 mg 3 x day 60-120 mg daily Controlled-release 10-40 mg 2 x day 0.025%-0.075% applied 3 or 4 x day 10-75 mg at night 25-75 mg at night 25-75 mg at night
Smoking
Encourage patient to quit
Peripheral p vasculature
Screen for PAD
Feet
Evaluate for plantarpressure Erythema, warmth, callus, or measured pressure Shoes Extrawide,custommolded Accommodatebonydeformities
American Diabetes Association. Diabetes Care. 2012:35(Suppl 1). Seaquist ER, et al. J Clin Endocrinol Metab. 2010;95:3103-3110.
2 2
Tricyclic drugs
Imipramine Nortriptyline
American Diabetes Association. Diabetes Care. 2012:35(Suppl 1). Watson CP, et al. Pain. 2003;105(1-2):71-78.
Michael is a 57-year-old, married African American patient with DM in for a 3-month follow-up visit. BP = 122/68 mm Hg; P = 66 Reg (no hx arrhythmias); BMI = 33
TC 198 mg/dL LDL 120 mg/dL HDL 39 mg/dL HbA1c 6.1% Vitamin D <30 ng/ml
True or False: Deficiency of vitamin D is associated with hypertension, DM, and metabolic syndrome. 1.True
BMI = body mass index.
2. False
Trials
13 observational studies (14 cohorts) and 18 trials No clinically significant effect of vitamin D supplementation at the dosages given
1. Giovannucci E, et al. Archives Int Med. 2008;168(11). 2. Wang TJ, et al. Circulation. 2008;117:503-511.
Conclusions: Calcium and vitamin D are 2 essential nutrients for bone health Little evidence of f other health benefit f
Life Stage Infants 0-6 Months Infants 6-12 months Children 1 to 8 years Adults 9-70 years Adults >70 years
Estimated Average Requirement 400 IU (10 ug) 400 IU (10 ug) 400 IU (10 ug) 400 IU (10 ug) 400 IU (10 ug)
Tolerable Upper Intake Level 1000 IU (25 ug) 1500 IU (38 ug) 2500-3000 IU (63-75 ug) 4000 IU (100 ug) 4000 IU (100 ug)
Dietary Reference Intakes for Calcium and Vitamin D. Institute of Medicine Consensus Report. November 30, 2010.
Ross AC, et al, eds. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press;2011:345-402.
Michael is your 57-year-old, married African American patient who comes in today to discuss labs you ordered.
BP = 122/68 mm Hg; P = 66 Reg (no hx arrhythmias); BMI = 33
TC 198 mg/dL LDL 120 mg/dL HDL 39 mg/dL HbA1C 7.1% T t t Testosterone 215 ng/ml
Your lab normal is 270-1070 ng/dL. You would: 1. Diagnose Michael with androgen deficiency. 2. Start Michael on testosterone. 3. Both 1 and 2. 4. None of the above
Statistics
25% of Med 5.6% sx 50% of DM >30 years, 1% a year
Manifestations
Bone loss Fractures Lose Muscle Lethargy Depression
Diagnosis
Need consistent symptoms Unequivocally low serum testosterone levels
Measure
Morning total testosterone level Confirm by repeating the measurement Possibly measure free or bioavailable testosterone level
RCTs = randomized control trials. Dhindsa S, et al. J Clin Endocrinol Metab. 2004;89:5462-5468.
The Endocrine Society. Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline. http://www.endo-society.org/guidelines/final/upload/FINAL-Androgens-in-MenStandalone.pdf. Accessed July 23, 2012.
Treatment
Aim for testosterone levels in mid-normal range Any approved formulation Choose based on
Patient's preference Consideration of pharmacokinetics Treatment burden Cost
IPSS = International Prostate Symptom Score. The Endocrine Society. Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline. http://www.endo-society.org/guidelines/final/upload/FINAL-Androgens-in-MenStandalone.pdf. Accessed July 23, 2012.
The Endocrine Society. Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline. http://www.endo-society.org/guidelines/final/upload/FINAL-Androgens-in-MenStandalone.pdf. Accessed July 23, 2012.
Antiplatelet
Recommendations vary depending upon risks and with newest data, risk/benefit discussion around GI bleeding needs to occur
Retinopathy
Control Co o BP and a d blood b ood sugar suga
Neuropathy
Control blood sugar
Vitamin D
Contributes to bone health
Testosterone
Treat symptomatic men