E.P. is a 62-year-old, 110-kg man with a history of T2DM, chronic stable angina, dyslipidemia, and smoking. His C.C. today is right upper thigh pain while walking around the block. The pain has gradually increased in the past 12 months, but only recently has become intolerable. The pain is relieved within minutes after he stops walking.  E.P. smokes 2 pack of cigarettes a day.
His most recent Lab results are significant for the following:

Total cholesterol 290 mg/dL; Fasting triglycerides 350 mg/dL; LDL 188 mg/dL; HDL 32 mg/dL;

SCr  0.8 mg/dL; BUN 18 mg/dL; Hgb A_1C  10.5%; Fasting glucose  190 mg/dL. His BP is 170/95 mm Hg & HR 89 beats/minutes.

His posterior tibial artery pulse is not palpable. A Doppler ultrasound study is performed and his ankle-to-brachial index (ABI) is 0.7 (normal: > 0.90).

E.P.’s medication list includes isosorbide mononitrate 60 mg daily, ASA 81 mg daily & ramipril 5 mg daily. His insulin doses have progressively increased to NPH insulin 40 units in the morning and 35 units in the evening.

 

Q 1: What risk factors and elements of E.P.’s presentation are consistent with a diagnosis of IC?

Mr. E.P’s history of thigh pain while walking that has gradually increased over months along with pain resolution at rest is classic for intermittent claudication.

Intermittent Claudication is often a symptom of peripheral artery disease (PAD). The peripheral arteries are the large vessels that deliver blood to your legs and arms. In PAD there is damage to the artery restricting blood to the limbs and usually caused by atherosclerosis. Additionally since his posterior tibial pulse is absent on palpation and he has an ABI of 0.7 this indicates PAD and IC.

Risk factors that Mr. E.P exhibits for PAD and IC are:

• Smoker > 50 years age
• Obese – even though we do not know his height with a weight of 110 kg (~243 lbs) we can assume he is overweight
• High blood pressure
• Type 2 DM
• Dyslipidemia

Q 2: What are the therapeutic goals in treating E.P. and what interventions should be initiated to prevent claudication pain and arrest progression of his disease?

Therapeutic goals for Mr. E.P:

• Total Cholesterol < 200
• LDL < 100
• HDL >40
• Triglycerides < 150
• Blood Pressure less than 140/90 mmHg
• Hgb A1C% < 7%

Interventions to be initiated for Mr. E. P:

• Most Important is Smoking cessation
• Diet/exercise counseling (structured exercise therapy)
  • To promote weight loss, risk of other disease, and improve functional status and quality of living.

• Management of dyslipidemia with high intensity statin therapy
  • A Meta-analysis showed that lipid-lowering therapy reduced disease progression and may help alleviate symptoms and improve total walking distance and pain-free walking distance

• Blood pressure control with medication management.
  • Increase Ramipril dose or add another antihypertensive medication
• Glycemic control with management of T2DM.
  • Proper adherence of insulin and monitoring of finger sticks.
• Start Cilostazol to improve symptoms of IC and increase walking distance.
• Screening for Atherosclerotic Disease in Other Vascular Beds for the Patient With PAD: duplex US for AAA
• Recommendation of Influenza Vaccination
• Counseled about self-foot exams and healthy foot behaviors

Q 3: Is lipid-lowering therapy indicated for E.P.?

According to the AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease, all patients with PAD should be treated with a statin medication. Additionally Mr. E.P’s 10-year ASCVD risk is 68.6 %, indicating he needs to be started on a high intensity statin. I would initially start him on atorvastatin 40mg, it will improve his dyslipidemia by reducing LDL and triglycerides, while also increasing HDL. Also statins can help with atherosclerosis as it can help alleviate symptoms of claudication. 

Q4:  How would you manage E.P.’s antihypertensive medication?

When it comes to managing Mr. E.P’s hypertension I would discuss lifestyle modifications such as smoking cessation, diet (low salt, decrease alcohol consumption, eat healthy) and exercise or physical activity to promote weight loss. Also I would inquire about the patient’s medication adherence especially since his hypertension is not under control. According to UpToDate and the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults the target BP for Mr. E.P should a goal of less than 130/80 mm Hg. My first intervention is to increase his dose of Ramipril from 5 mg to 10 mg daily and reevaluate his BP in one month. If it is still elevated I would then add a second antihypertensive medication like amlodipine 2.5mg since he is elderly and the CCB is used as a secondary agent. Also with his history of chronic stable angina a CCB can also be beneficial.

Q5: Will improving E.P.’s diabetes control or slow the progression of his PAD? What changes in his diabetes management do you recommend?

The best way to prevent claudication or slow the progression of PAD is to maintain a healthy lifestyle and also control certain risk factors/medical conditions. So second to quitting smoking, Mr. E.P should manage his T2DM by keeping his blood sugar in good control. This is because having elevated blood glucose can increase ones risk of atherosclerosis, which is a big contributor to PAD and also CAD. For Mr. E.P a recommended HbA1c would be <7.0%. Again a discussion of lifestyle changes and medication adherence should be examined but additionally since his HbA1c is 10.5% and fasting glucose is 190 mg/dL is very high, I would add another medication. Since he is taking the NPH as basal insulin, I would add a GLP-1 receptor agonist like Liraglutide 1.2 mg once daily. Liraglutide would help reduce his HbA1c, fasting glucose, weight, and it has shown to have cardiovascular benefits.

Liraglutide is available in prefilled pens and the initial does is 0.6 mg once daily for the first week to reduce GI side effects. Then the dose is increased to 1.2 mg once daily for one week. It can be increased to max 1.8 mg/day if blood glucose goal is not reached.

Q6: Is E.P.’s ASA therapy beneficial for preventing further complications of IC? Are there any medications that can be used to increase the walking ability of E.P.?

As per the 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease, antiplatelet therapy with aspirin alone (75-325 mg daily) or clopidogrel alone (75mg daily) is recommended to educe MI, stroke, and vascular death in patients with symptomatic PAD. Although most data points towards modest improvement or no improvement in claudication symptoms, I would keep Mr. E.P on ASA 81 mg for the prevention of CHD and stroke.

For that management of IC, Cilostazol, a phosphodiesterase inhibitor can suppress platelet aggregation and have direct arterial vasodilator. Thus it is an effective treatment for leg symptoms and walking impairment due to claudication. However, side effects should be monitored which include headache, diarrhea, dizziness, and palpitations.

Medication Profile

• Isosorbide Mononitrate 60 mg Daily
• ASA 81 mg PO Daily
• NPH insulin 40 units in the morning and 35 units in the evening
• Ramipril 10 mg PO Daily
• Atorvastatin 40 mg PO Daily
• Liraglutide 1.2 mg SC Daily
• Cilastozol 100 mg BID

Resources:

1. https://www.ahajournals.org/doi/epub/10.1161/CIR.0000000000000470
2. http://www.cvriskcalculator.com/calculated?age=62&gender=1&race=0&total-chol=290&hdl=32&sbp=170&dbp=95&treated=0&diabetes=1&smoker=1
3. https://www.ahajournals.org/doi/10.1161/HYP.0000000000000066
4. https://www.uptodate.com/contents/goal-blood-pressure-in-adults-with-hypertension?search=hypertension%20and%20peripheral%20artery%20disease&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H2839714254
5. https://www.uptodate.com/contents/management-of-persistent-hyperglycemia-in-type-2-diabetes-mellitus
6. https://www.uptodate.com/contents/management-of-claudication-due-to-peripheral-artery-disease