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CME test answers therapeutic options for cardiometabolic risk factors
Clinical Cornerstone
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THERAPEUTIC O P T I O N S FOR CARDIOMETABOLIC RISK FACTORS
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Vol. 9, Supplement 1
CME Test Answers THERAPEUTIC OPTIONS FOR C A R D I O M E T A B O L I C RISK F A C T O R S 1. a
Every 20/10-mm Hg increase in blood pressure is associated with a doubling of CVD risk. In the Framingham Heart Study, individuals with high-normal blood pressure levels (130/85-139/89 mm Hg) had at least a 2-fold greater increase in the risk of CVD than did those with optimal blood pressure levels (<120/80 mm Hg). 2. d
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure considers optimal blood pressure to be <120/80 mm Hg, blood pressure levels of 120/80 to 139/89 mm Hg to be prehypertension, and blood pressure levels >140/90 mm Hg to be hypertension. 3. b Every patient visit is an opportunity to assess BMI and waist circumference. Patients with a BMI of 25 to 29.9 kg/m2 are considered overweight, and those with a BMI of >30 kg/m2 are considered obese. A waist circumference >40 inches (102 cm) in men and >35 inches (88 cm) in women is associated with an increased risk of CVD. 4. d
A CVD risk factor that is becoming more prevalent is diabetes. The increase in the prevalence of diabetes is closely related to the increased prevalence of obesity; indeed, -90% of type 2 DM is attributable to excess body weight. Individuals with diabetes, impaired fasting glucose, or impaired glucose tolerance are at an increased risk of developing CVD, as well as an increased risk of dying from it. An analysis of the age-adjusted death rate for CHD from 1980 to 2000 demonstrated that an increase in the prevalence of diabetes from 6.5% in 1980 to 9.4% in 2000 accounted for a 9.8% increase in deaths due to CHD over the same period. 5. a
Although increased levels of LDL-C and triglycerides and decreased levels of HDL-C have all been associated $45
with an increased risk of CVD, the greatest risk is associated with increased levels of LDL-C. Consequently, lipid goals are generally stated in terms of LDL-C. 6. d
For all patients with elevated LDL-C levels, lifestyle changes such as reduced intake of saturated fats and cholesterol, weight reduction, and increased physical activity are recommended. Pharmacotherapy is recommended for those with CHD or CHD risk equivalents if their LDL-C level is >130 mg/dL. Pharmacotherapy is recommended for individuals with >2 CHD risk factors if their LDL-C level is >130 mg/dL and their 10-year risk for CHD (based on Framingham risk scoring) is 10% to 20% or if their LDL-C level is >160 mg/dL and their 10-year risk for CHD is <10%. For individuals with <1 risk factor, pharmacotherapy is recommended if their LDL-C level is >190 mg/dL. Treatment with lipid-lowering agents to reduce LDL-C levels has been associated with a reduction in the risk of CVD. 7. C
Although obesity is a risk factor for insulin resistance, type 2 DM, and CVD, not every overweight/obese patient is at high risk. For any given amount of total body fat, individuals with a selective excess of abdominal adipose tissue (mainly intra-abdominal or VAT) are at substantially higher risk of being characterized by insulin resistance, the components of metabolic syndrome, and type 2 DM. 8. a
True. There is evidence that adipose tissue not only is involved in the storage and mobilization of lipids, but also that it is a remarkable endocrine organ releasing numerous molecules, including various hormones (eg, leptin and adiponectin) and several proinflammatory cytokines (eg, interleukin-6 and tumor necrosis factor-(,). Compared with levels of proinflammatory adipokines, which are elevated in obese individuals, adiponectin levels are reduced in these individuals, particularly among
Clinical Cornerstone
•
THERAPEUTIC O P T I O N S FOR C A R D I O M E T A B O L I C RISK FACTORS
•
Vol. 9, Supplement 1
CME Test Answers THERAPEUTIC OPTIONS FOR C A R D I O M E T A B O L I C RISK F A C T O R S those with excess VAT. Because adiponectin improves insulin signaling, the low adiponectin levels observed in viscerally obese patients could be one of the key factors responsible for their diabetogenic and atherogenic metabolic risk profile. 9. d
Weight gain during childhood and adolescence or during early adult life seems to have a significant impact on the development of type 2 DM, metabolic syndrome, and CVD, even within the normal BMI range. High visceral and low abdominal subcutaneous fat stores in the obese adolescent are a determinant of an adverse metabolic phenotype. These adolescents are not necessarily the most severely obese, yet they suffer from severe metabolic complications of obesity and are at high risk for developing metabolic syndrome. 10. a
True. Limited evidence from a number of studies that used imaging techniques to quantify changes in abdominal obesity suggests a beneficial influence of physical activity on reduction of abdominal fat and VAT in overweight and obese subjects. Reductions in VAT and total abdominal fat may occur in the absence of changes in body mass and waist circumference. Because the deposition of fat in the abdomen and in nonadipose tissues such as liver and muscle plays a major role in the development of obesity-related health risks, these depots have emerged as alternative targets for obesity treatment. 11. d Pharmacologic therapy can be offered to obese patients who have failed to achieve their weight loss goals through diet and exercise alone, and it should be considered for patients with either a BMI >30 kg/m2 or a BMI >27 kg/m2 with obesity-related risk factors or disease. Because it is now recognized that obesity is a chronic disease, only those approaches that induce safe long-term weight reduction should be considered valuable treatment strategies for obese subjects. Special attention should be paid $46
to the beneficial metabolic effects resulting from even moderate weight loss and to possible additional effects beyond weight reduction. 12. a True. Under normal conditions, insulin represses hepatic glucose production overnight, regulating FPG levels. Insulin also represses glucose production during food consumption and removes glucose from the circulation by increasing hepatic and skeletal muscle uptake. In diabetic patients, impaired insulin secretion allows the liver to overproduce glucose, which leads to higher FPG levels. When coupled with insulin resistance, plasma glucose levels are increased both postprandially and in the fasting state as glucose uptake in skeletal muscle is reduced. 13. a During the postprandial period, carbohydrates are absorbed and glucose concentrations rise. Considering that people generally eat 3 meals a day, 3 postprandial periods of -4 to 5 hours each are observed; therefore, people spend more than half of their day in a postprandial state. The postprandial state overlaps with a postabsorptive state lasting -6 hours, during which time glucose is removed from the circulation. In reality, then, only -2 hours at the end of an individual's night are spent in a true fasting state. Consequently, the fasting state may not accurately reflect a patient's 24-hour metabolic profile. Since most of a patient's day is spent in a postprandial state, postprandial measurements may be more useful for monitoring. 14. d
Chronic hyperglycemia is one cause of endothelial dysfunction. Endothelial dysfunction contributes to the development of atherosclerosis and precedes the clinically vascular pathology that leads to CVD. In addition to postprandial hyperglycemia, increased triglyceride levels associated with type 2 DM work through independent mechanisms to further decrease endothelial cell function.
Clinical Cornerstone
•
THERAPEUTIC O P T I O N S FOR CARDIOMETABOLIC RISK FACTORS
•
Vol. 9, Supplement 1
CME Test Answers THERAPEUTIC OPTIONS FOR C A R D I O M E T A B O L I C RISK F A C T O R S 15. b
16. a
False. Elevated FPG and PPG levels contribute to the elevated HbAlc concentrations observed in patients with type 2 DM to varying degrees. PPG excursions are the predominant form of hyperglycemia in patients whose HbAlc is <7.3%, whereas a pattern of predominantly fasting hyperglycemia is observed among patients with HbAlc >8.5%. This points to the importance of basalbolus insulin therapy for patients who are unable to achieve HbAlc <7.0% with lifestyle intervention alone or lifestyle intervention plus metformin, or for patients who present with weight loss and glucose values between 250 and 300 mg/dL.
In a basal-bolus insulin regimen, rapid-acting insulin analogs, such as glulisine, lispro, and aspart, which begin to work in -15 minutes, limit PPG fluctuations. They provide increased dosing flexibility and decrease the possibility of severe postprandial hypoglycemia, especially in individuals attempting to maintain normoglycemia. Intermediate-acting insulins (NPH and lente) and long-acting insulins (glargine and detemir) mimic basal insulin secretion to control FPG levels.
$47
•
THERAPEUTIC O P T I O N S FOR CARDIOMETABOLIC RISK FACTORS
•
Vol. 9, Supplement 1
CME Test Answers THERAPEUTIC OPTIONS FOR C A R D I O M E T A B O L I C RISK F A C T O R S 1. a
Every 20/10-mm Hg increase in blood pressure is associated with a doubling of CVD risk. In the Framingham Heart Study, individuals with high-normal blood pressure levels (130/85-139/89 mm Hg) had at least a 2-fold greater increase in the risk of CVD than did those with optimal blood pressure levels (<120/80 mm Hg). 2. d
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure considers optimal blood pressure to be <120/80 mm Hg, blood pressure levels of 120/80 to 139/89 mm Hg to be prehypertension, and blood pressure levels >140/90 mm Hg to be hypertension. 3. b Every patient visit is an opportunity to assess BMI and waist circumference. Patients with a BMI of 25 to 29.9 kg/m2 are considered overweight, and those with a BMI of >30 kg/m2 are considered obese. A waist circumference >40 inches (102 cm) in men and >35 inches (88 cm) in women is associated with an increased risk of CVD. 4. d
A CVD risk factor that is becoming more prevalent is diabetes. The increase in the prevalence of diabetes is closely related to the increased prevalence of obesity; indeed, -90% of type 2 DM is attributable to excess body weight. Individuals with diabetes, impaired fasting glucose, or impaired glucose tolerance are at an increased risk of developing CVD, as well as an increased risk of dying from it. An analysis of the age-adjusted death rate for CHD from 1980 to 2000 demonstrated that an increase in the prevalence of diabetes from 6.5% in 1980 to 9.4% in 2000 accounted for a 9.8% increase in deaths due to CHD over the same period. 5. a
Although increased levels of LDL-C and triglycerides and decreased levels of HDL-C have all been associated $45
with an increased risk of CVD, the greatest risk is associated with increased levels of LDL-C. Consequently, lipid goals are generally stated in terms of LDL-C. 6. d
For all patients with elevated LDL-C levels, lifestyle changes such as reduced intake of saturated fats and cholesterol, weight reduction, and increased physical activity are recommended. Pharmacotherapy is recommended for those with CHD or CHD risk equivalents if their LDL-C level is >130 mg/dL. Pharmacotherapy is recommended for individuals with >2 CHD risk factors if their LDL-C level is >130 mg/dL and their 10-year risk for CHD (based on Framingham risk scoring) is 10% to 20% or if their LDL-C level is >160 mg/dL and their 10-year risk for CHD is <10%. For individuals with <1 risk factor, pharmacotherapy is recommended if their LDL-C level is >190 mg/dL. Treatment with lipid-lowering agents to reduce LDL-C levels has been associated with a reduction in the risk of CVD. 7. C
Although obesity is a risk factor for insulin resistance, type 2 DM, and CVD, not every overweight/obese patient is at high risk. For any given amount of total body fat, individuals with a selective excess of abdominal adipose tissue (mainly intra-abdominal or VAT) are at substantially higher risk of being characterized by insulin resistance, the components of metabolic syndrome, and type 2 DM. 8. a
True. There is evidence that adipose tissue not only is involved in the storage and mobilization of lipids, but also that it is a remarkable endocrine organ releasing numerous molecules, including various hormones (eg, leptin and adiponectin) and several proinflammatory cytokines (eg, interleukin-6 and tumor necrosis factor-(,). Compared with levels of proinflammatory adipokines, which are elevated in obese individuals, adiponectin levels are reduced in these individuals, particularly among
Clinical Cornerstone
•
THERAPEUTIC O P T I O N S FOR C A R D I O M E T A B O L I C RISK FACTORS
•
Vol. 9, Supplement 1
CME Test Answers THERAPEUTIC OPTIONS FOR C A R D I O M E T A B O L I C RISK F A C T O R S those with excess VAT. Because adiponectin improves insulin signaling, the low adiponectin levels observed in viscerally obese patients could be one of the key factors responsible for their diabetogenic and atherogenic metabolic risk profile. 9. d
Weight gain during childhood and adolescence or during early adult life seems to have a significant impact on the development of type 2 DM, metabolic syndrome, and CVD, even within the normal BMI range. High visceral and low abdominal subcutaneous fat stores in the obese adolescent are a determinant of an adverse metabolic phenotype. These adolescents are not necessarily the most severely obese, yet they suffer from severe metabolic complications of obesity and are at high risk for developing metabolic syndrome. 10. a
True. Limited evidence from a number of studies that used imaging techniques to quantify changes in abdominal obesity suggests a beneficial influence of physical activity on reduction of abdominal fat and VAT in overweight and obese subjects. Reductions in VAT and total abdominal fat may occur in the absence of changes in body mass and waist circumference. Because the deposition of fat in the abdomen and in nonadipose tissues such as liver and muscle plays a major role in the development of obesity-related health risks, these depots have emerged as alternative targets for obesity treatment. 11. d Pharmacologic therapy can be offered to obese patients who have failed to achieve their weight loss goals through diet and exercise alone, and it should be considered for patients with either a BMI >30 kg/m2 or a BMI >27 kg/m2 with obesity-related risk factors or disease. Because it is now recognized that obesity is a chronic disease, only those approaches that induce safe long-term weight reduction should be considered valuable treatment strategies for obese subjects. Special attention should be paid $46
to the beneficial metabolic effects resulting from even moderate weight loss and to possible additional effects beyond weight reduction. 12. a True. Under normal conditions, insulin represses hepatic glucose production overnight, regulating FPG levels. Insulin also represses glucose production during food consumption and removes glucose from the circulation by increasing hepatic and skeletal muscle uptake. In diabetic patients, impaired insulin secretion allows the liver to overproduce glucose, which leads to higher FPG levels. When coupled with insulin resistance, plasma glucose levels are increased both postprandially and in the fasting state as glucose uptake in skeletal muscle is reduced. 13. a During the postprandial period, carbohydrates are absorbed and glucose concentrations rise. Considering that people generally eat 3 meals a day, 3 postprandial periods of -4 to 5 hours each are observed; therefore, people spend more than half of their day in a postprandial state. The postprandial state overlaps with a postabsorptive state lasting -6 hours, during which time glucose is removed from the circulation. In reality, then, only -2 hours at the end of an individual's night are spent in a true fasting state. Consequently, the fasting state may not accurately reflect a patient's 24-hour metabolic profile. Since most of a patient's day is spent in a postprandial state, postprandial measurements may be more useful for monitoring. 14. d
Chronic hyperglycemia is one cause of endothelial dysfunction. Endothelial dysfunction contributes to the development of atherosclerosis and precedes the clinically vascular pathology that leads to CVD. In addition to postprandial hyperglycemia, increased triglyceride levels associated with type 2 DM work through independent mechanisms to further decrease endothelial cell function.
Clinical Cornerstone
•
THERAPEUTIC O P T I O N S FOR CARDIOMETABOLIC RISK FACTORS
•
Vol. 9, Supplement 1
CME Test Answers THERAPEUTIC OPTIONS FOR C A R D I O M E T A B O L I C RISK F A C T O R S 15. b
16. a
False. Elevated FPG and PPG levels contribute to the elevated HbAlc concentrations observed in patients with type 2 DM to varying degrees. PPG excursions are the predominant form of hyperglycemia in patients whose HbAlc is <7.3%, whereas a pattern of predominantly fasting hyperglycemia is observed among patients with HbAlc >8.5%. This points to the importance of basalbolus insulin therapy for patients who are unable to achieve HbAlc <7.0% with lifestyle intervention alone or lifestyle intervention plus metformin, or for patients who present with weight loss and glucose values between 250 and 300 mg/dL.
In a basal-bolus insulin regimen, rapid-acting insulin analogs, such as glulisine, lispro, and aspart, which begin to work in -15 minutes, limit PPG fluctuations. They provide increased dosing flexibility and decrease the possibility of severe postprandial hypoglycemia, especially in individuals attempting to maintain normoglycemia. Intermediate-acting insulins (NPH and lente) and long-acting insulins (glargine and detemir) mimic basal insulin secretion to control FPG levels.
$47