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Acute Leriche Syndrome In A Young Female: First Manifestation Of Atherosclerosis
706 Table
Journal of Clinical Lipidology, Vol 10, No 3, June 2016 Fasting lipids at Baseline and Follow-up
Mean (±SD) or Median (IQR) Surgical BMI Total Cholesterol HDL-C LDL-C Triglycerides TG / HDL-C Non-Surgical BMI Total Cholesterol HDL-C LDL-C Triglycerides TG / HDL-C
n
Baseline
Follow-up
% Change
p-value
58 50 50 50 50 50
59 172 35 108 127 3.7
(610) (633) (67) (626) (99,182) (2.6,5.2)
42 172 57 95 76 1.5
(612) (643) (618) (632) (60,123) (1.0,2.2)
-29% -5% +53% -18% -35% -57%
,0.01 0.70 ,0.01 0.02 ,0.01 ,0.01
30 25 24 23 25 24
52 171 40 99 115 2.7
(68) (639) (69) (624) (77,152) (1.7,3.9)
57 170 41 106 116 2.4
(616) (633) (69) (630) (66,148) (1.5,3.7)
+8% +2% +5% +6% -6% -7%
0.03 0.83 0.74 0.36 0.17 0.33
32% lower than baseline (p,0.01). All lipids (except total cholesterol) significantly improved with the largest changes in HDL-C and TG/HDL-C ratio (a decrease of 35% and 57%, respectively). In the non-surgical comparison group (n530, 47% Caucasian, 73% female) age 1562 at baseline and 2262 years at follow-up, BMI increased by 6.2% and lipid parameters were similar. See Table. Conclusions: This is the longest term and most complete follow-up of adolescents following RYGB. Weight loss was durably maintained and significant improvements in lipid profile were observed after RYGB. Whether these lipid improvements translate into reductions in atherosclerosis and cardiovascular events overtime remains to be determined. Abstract won fourth place Young Investigator Award.
Pathophysiology of Atherosclerosis
presented to ER with bilateral leg pain for 1 month. Pain was described as burning, radiating from buttocks to calves, exacerbated with walking and associated with tingling and numbness. Upon initial evaluation she was discharged from ER with diagnosis of sciatica. She returned 1 month later with excruciating pain along with blood pressure 188/101 mm Hg and heart rate 109 beats per minute. Examination revealed purplish red discoloration of skin in both lower extremities below hip joint suggestive of livedo reticularis. They were also cold to touch with absent femoral pulses bilaterally. Methods: Lipid panel showed total cholesterol 254 mg/ dl, LDL 181 mg/dl, HDL 36 mg/dl and triglyceride 231 mg/ dl. Creatinine was 1.95 mg/dl and creatine kinase was elevated at 11,875 unit/L. She underwent CT abdomen with contrast which showed complete occlusion of infrarenal abdominal aorta about 5 cm above the common iliac artery bifurcation with no collateral vascularity and atherosclerotic mural calcifications in thoracic and abdominal aorta (see Figure).
173 Acute Leriche Syndrome In A Young Female: First Manifestation Of Atherosclerosis Mihir Barvalia, MD, Jana Mckenzie, DO, Lilia Tcharnaia, MD, Marc Cohen, MD, Najam Wasty, MD, (Cincinnati, OH)
Lead Author’s Financial Disclosures: None Study Funding: None Background/Synopsis: Advancing age, diabetes mellitus, smoking and dyslipidemia are major risk factors for peripheral artery disease (PAD). We encountered a case of a young female with total occlusion of abdominal aorta as first manifestation of atherosclerosis. Objective/Purpose: A 48-year-old African American woman with long standing history of systemic hypertension
Figure
Abstracts
707
Results: She then underwent aortic thrombectomy and aorto-bifemoral bypass with grafting. Following surgery, patient had no leg pain and was discharged home on statin and anti-hypertensive drugs. Conclusions: PAD often goes undetected in clinical practice. Even asymptomatic PAD patients have a high mortality. As this case demonstrates, severe PAD can be an initial manifestation of hypercholesterolemia and atherosclerosis in a female. Fortunately our patient had an excellent outcome despite the delay in diagnosis. In conclusion, leriche syndrome should be promptly diagnosed and treated. 174 Antisense Mediated Lowering of Plasma Apolipoprotein C-III by Volanesorsen Improves Dyslipidemia and Insulin Sensitivity in Type 2 Diabetes Andres Digenio, MD, PhD, Richard Dunbar, MD, Veronica Alexander, PhD, Marcus Hompesch, MD, Linda Morrow, MD, Richard Lee, PhD, Mark Graham, MS, Steven Hughes, MB, BS, Rosie Yu, PhD, Walter Singleton, MD, Brenda Baker, PhD, Sanjay Bhanot, MD, PhD, Rosanne Crooke, PhD, (Cambridge, MA)
Lead Author’s Financial Disclosures: Dr. Digenio is an employee of Akcea Therapeutics, a subsidiary of Ionis Pharmaceuticals Inc. Study Funding: None Background/Synopsis: Insulin resistance states usually seen in the context of obesity and type 2 diabetes are commonly associated with a metabolic dyslipidemia that amplifies cardiovascular disease risk. While it is well established that insulin resistance drives dyslipidemia, there is growing evidence that the elevation in plasma triglycerides (TG) and reduction in high-density lipoprotein cholesterol (HDL-C) accompanying insulin resistance states may exacerbate the insulin resistant phenotype. ApoC-III has been identified as a key modulator of plasma TG concentrations in animal models and in humans. Treating normolipidemic and hypertriglyceridemic human subjects with volanesorsen (ISIS 304801), profoundly reduced plasma apoC-III protein and plasma TG levels. Objective/Purpose: To determine the effects of volanesorsen (ISIS 304801), a second generation 2’-O-methoxyethyl chimeric antisense inhibitor of apolipoprotein C-III (apoC-III), on triglyceride (TG) levels and insulin resistance in patients with type 2 diabetes. Methods: A randomized, double-blind, placebocontrolled trial was performed in 15 adult patients with type 2 diabetes (HbA1c .7.5% [58 mmol/mol]) and hypertriglyceridemia (TG.200 and ,500 mg/dL). Patients were randomized 2:1 to receive volanesorsen 300 mg or placebo for a total of 15 subcutaneous (SC) weekly doses. Glucose handling and insulin sensitivity were measured
Figure Volanesorsen 300 mg Improves Whole-Body Insulin Sensitivity on Clamp. In this boxplot the horizontal line represents the median, the box the 25th and 75th percentiles and the whiskers the 10th and 90th percentiles. The colored lines between baseline and treated clamps demonstrate the response of individual patients. A green line indicates a 20% or greater improvement in insulin sensitivity, whereas a red line indicates 20% or greater worsening from baseline.
before and after treatment using a two-step hyperinsulinemic-euglycemic clamp procedure. Results: Treatment with volanesorsen significantly reduced plasma apoC-III (-88%, p50.02) and TG (-69%, p50.02) levels, and raised high-density lipoprotein cholesterol (HDL-C) (+42%, p50.03), compared to placebo. These changes were accompanied by a 57% improvement in insulin sensitivity (p,0.001), attributable to accelerated peripheral glucose disposal (+30%, p50.02) (Figure 1). Importantly, we found a strong relationship between enhanced insulin sensitivity and both plasma apoC-III (r5-0.70, p,0.05) and TG (r5-0.80, p,0.01) suppression. Improved insulin sensitivity was sufficient to significantly lower glycated albumin (-1.73%, p50.034) and fructosamine (-38.7 micromol/L, p50.045) at the end of dosing, and HbA1c (-0.44%, p50.025) 3 months post dosing. Conclusions: Volanesorsen reduced plasma apoC-III and TG, while raising HDL-C levels. Importantly, glucose disposal, insulin sensitivity and integrative markers of
Journal of Clinical Lipidology, Vol 10, No 3, June 2016 Fasting lipids at Baseline and Follow-up
Mean (±SD) or Median (IQR) Surgical BMI Total Cholesterol HDL-C LDL-C Triglycerides TG / HDL-C Non-Surgical BMI Total Cholesterol HDL-C LDL-C Triglycerides TG / HDL-C
n
Baseline
Follow-up
% Change
p-value
58 50 50 50 50 50
59 172 35 108 127 3.7
(610) (633) (67) (626) (99,182) (2.6,5.2)
42 172 57 95 76 1.5
(612) (643) (618) (632) (60,123) (1.0,2.2)
-29% -5% +53% -18% -35% -57%
,0.01 0.70 ,0.01 0.02 ,0.01 ,0.01
30 25 24 23 25 24
52 171 40 99 115 2.7
(68) (639) (69) (624) (77,152) (1.7,3.9)
57 170 41 106 116 2.4
(616) (633) (69) (630) (66,148) (1.5,3.7)
+8% +2% +5% +6% -6% -7%
0.03 0.83 0.74 0.36 0.17 0.33
32% lower than baseline (p,0.01). All lipids (except total cholesterol) significantly improved with the largest changes in HDL-C and TG/HDL-C ratio (a decrease of 35% and 57%, respectively). In the non-surgical comparison group (n530, 47% Caucasian, 73% female) age 1562 at baseline and 2262 years at follow-up, BMI increased by 6.2% and lipid parameters were similar. See Table. Conclusions: This is the longest term and most complete follow-up of adolescents following RYGB. Weight loss was durably maintained and significant improvements in lipid profile were observed after RYGB. Whether these lipid improvements translate into reductions in atherosclerosis and cardiovascular events overtime remains to be determined. Abstract won fourth place Young Investigator Award.
Pathophysiology of Atherosclerosis
presented to ER with bilateral leg pain for 1 month. Pain was described as burning, radiating from buttocks to calves, exacerbated with walking and associated with tingling and numbness. Upon initial evaluation she was discharged from ER with diagnosis of sciatica. She returned 1 month later with excruciating pain along with blood pressure 188/101 mm Hg and heart rate 109 beats per minute. Examination revealed purplish red discoloration of skin in both lower extremities below hip joint suggestive of livedo reticularis. They were also cold to touch with absent femoral pulses bilaterally. Methods: Lipid panel showed total cholesterol 254 mg/ dl, LDL 181 mg/dl, HDL 36 mg/dl and triglyceride 231 mg/ dl. Creatinine was 1.95 mg/dl and creatine kinase was elevated at 11,875 unit/L. She underwent CT abdomen with contrast which showed complete occlusion of infrarenal abdominal aorta about 5 cm above the common iliac artery bifurcation with no collateral vascularity and atherosclerotic mural calcifications in thoracic and abdominal aorta (see Figure).
173 Acute Leriche Syndrome In A Young Female: First Manifestation Of Atherosclerosis Mihir Barvalia, MD, Jana Mckenzie, DO, Lilia Tcharnaia, MD, Marc Cohen, MD, Najam Wasty, MD, (Cincinnati, OH)
Lead Author’s Financial Disclosures: None Study Funding: None Background/Synopsis: Advancing age, diabetes mellitus, smoking and dyslipidemia are major risk factors for peripheral artery disease (PAD). We encountered a case of a young female with total occlusion of abdominal aorta as first manifestation of atherosclerosis. Objective/Purpose: A 48-year-old African American woman with long standing history of systemic hypertension
Figure
Abstracts
707
Results: She then underwent aortic thrombectomy and aorto-bifemoral bypass with grafting. Following surgery, patient had no leg pain and was discharged home on statin and anti-hypertensive drugs. Conclusions: PAD often goes undetected in clinical practice. Even asymptomatic PAD patients have a high mortality. As this case demonstrates, severe PAD can be an initial manifestation of hypercholesterolemia and atherosclerosis in a female. Fortunately our patient had an excellent outcome despite the delay in diagnosis. In conclusion, leriche syndrome should be promptly diagnosed and treated. 174 Antisense Mediated Lowering of Plasma Apolipoprotein C-III by Volanesorsen Improves Dyslipidemia and Insulin Sensitivity in Type 2 Diabetes Andres Digenio, MD, PhD, Richard Dunbar, MD, Veronica Alexander, PhD, Marcus Hompesch, MD, Linda Morrow, MD, Richard Lee, PhD, Mark Graham, MS, Steven Hughes, MB, BS, Rosie Yu, PhD, Walter Singleton, MD, Brenda Baker, PhD, Sanjay Bhanot, MD, PhD, Rosanne Crooke, PhD, (Cambridge, MA)
Lead Author’s Financial Disclosures: Dr. Digenio is an employee of Akcea Therapeutics, a subsidiary of Ionis Pharmaceuticals Inc. Study Funding: None Background/Synopsis: Insulin resistance states usually seen in the context of obesity and type 2 diabetes are commonly associated with a metabolic dyslipidemia that amplifies cardiovascular disease risk. While it is well established that insulin resistance drives dyslipidemia, there is growing evidence that the elevation in plasma triglycerides (TG) and reduction in high-density lipoprotein cholesterol (HDL-C) accompanying insulin resistance states may exacerbate the insulin resistant phenotype. ApoC-III has been identified as a key modulator of plasma TG concentrations in animal models and in humans. Treating normolipidemic and hypertriglyceridemic human subjects with volanesorsen (ISIS 304801), profoundly reduced plasma apoC-III protein and plasma TG levels. Objective/Purpose: To determine the effects of volanesorsen (ISIS 304801), a second generation 2’-O-methoxyethyl chimeric antisense inhibitor of apolipoprotein C-III (apoC-III), on triglyceride (TG) levels and insulin resistance in patients with type 2 diabetes. Methods: A randomized, double-blind, placebocontrolled trial was performed in 15 adult patients with type 2 diabetes (HbA1c .7.5% [58 mmol/mol]) and hypertriglyceridemia (TG.200 and ,500 mg/dL). Patients were randomized 2:1 to receive volanesorsen 300 mg or placebo for a total of 15 subcutaneous (SC) weekly doses. Glucose handling and insulin sensitivity were measured
Figure Volanesorsen 300 mg Improves Whole-Body Insulin Sensitivity on Clamp. In this boxplot the horizontal line represents the median, the box the 25th and 75th percentiles and the whiskers the 10th and 90th percentiles. The colored lines between baseline and treated clamps demonstrate the response of individual patients. A green line indicates a 20% or greater improvement in insulin sensitivity, whereas a red line indicates 20% or greater worsening from baseline.
before and after treatment using a two-step hyperinsulinemic-euglycemic clamp procedure. Results: Treatment with volanesorsen significantly reduced plasma apoC-III (-88%, p50.02) and TG (-69%, p50.02) levels, and raised high-density lipoprotein cholesterol (HDL-C) (+42%, p50.03), compared to placebo. These changes were accompanied by a 57% improvement in insulin sensitivity (p,0.001), attributable to accelerated peripheral glucose disposal (+30%, p50.02) (Figure 1). Importantly, we found a strong relationship between enhanced insulin sensitivity and both plasma apoC-III (r5-0.70, p,0.05) and TG (r5-0.80, p,0.01) suppression. Improved insulin sensitivity was sufficient to significantly lower glycated albumin (-1.73%, p50.034) and fructosamine (-38.7 micromol/L, p50.045) at the end of dosing, and HbA1c (-0.44%, p50.025) 3 months post dosing. Conclusions: Volanesorsen reduced plasma apoC-III and TG, while raising HDL-C levels. Importantly, glucose disposal, insulin sensitivity and integrative markers of