Triglyceride Content of HDL Predicts Statin Myotoxicity

VANCOUVER, B.C. – Information about a patient’s risk of developing statin-induced myotoxicity may come from a surprising source: the composition of his or her high-density lipoprotein particles, a study has shown.

In the observational study of 670 patients, those having higher levels of HDL particles rich in triglycerides before starting statins were 3-21 times more likely to develop various types of myotoxicity while on these medications.

“These results suggest an association between HDL-triglyceride concentration at baseline and markers of statin intolerance,” lead investigator Dr. Tarek Bouhali said at the annual World Congress on Heart Disease sponsored by the International Academy of Cardiology.

“Right now, we can’t tell what the mechanism is,” he commented. “But ... HDL is a heterogeneous group of lipoproteins and is not only cholesterol,” and in this setting, it appears that heterogeneity may be useful for risk stratification.

Skeletal muscle adverse events are the leading complication of statin therapy, according to Dr. Bouhali. “Muscular side effects are usually mild and reversible; however, knowledge of the underlying mechanism and risk factors is required for prompt identification and proper management for these side effects.”

Furthermore, he noted, understanding and preventing statin adverse effects are important because side effects can lead to both reduced compliance and increased health care costs.

The investigators collected fasting plasma samples from adult French Canadian patients who were about to start lipid-lowering therapy and were receiving care according to American Heart Association guidelines. The samples were ultracentrifuged to determine levels of cholesterol and triglyceride associated with HDL particles.

The study patients were 50 years old on average, and 63% were male. About 12% were taking statins in combination with other lipid-lowering medications (fibrates, bile acid sequestrants, nicotinic acid, or inhibitors of cholesterol absorption).

Overall, 22% of the patients had at least one adverse effect of any type (muscular or nonmuscular), reported Dr. Bouhali of the University of Montreal and the lead investigator with the ECOGENE-21 project.

In terms of the muscular adverse effects, 20% of patients developed myalgia, 7% had a creatine kinase level of 300 U/L or higher, 3% had trace proteinuria or myoglobinuria, and 2% had a creatine kinase level of 500 U/L or higher.

After adjustment for age, sex, statin dose, and concomitant medications, a higher plasma HDL-triglyceride level before starting treatment was associated with a greater risk of myotoxicity, and especially the more severe forms, noted Dr. Bouhali.

Specifically, the log10-transformed HDL-triglyceride level in millimoles per liter was significantly associated with the development of myalgia (odds ratio, 2.9); a creatine kinase level of 300 U/L or higher (OR, 6.0); proteinuria or myoglobinuria (OR, 12.6); and a creatine kinase level of 500 U/L or higher (OR, 20.9).

In addition, a higher HDL-triglyceride level at baseline was associated with a borderline increase in the risk of any (muscular or nonmuscular) adverse effect (OR, 2.5; P = .065).

In contrast, the level of HDL cholesterol was not significantly associated with the likelihood of statin adverse effects.

The study’s findings should be validated and replicated in other populations, said Dr. Bouhali.

In addition, “further mechanistic studies are needed to explore the implication of HDL particle composition in the development of statin intolerance,” he said in comments provided by e-mail.

Dr. Bouhali reported that he had no relevant conflicts of interest.

VANCOUVER, B.C. – Information about a patient’s risk of developing statin-induced myotoxicity may come from a surprising source: the composition of his or her high-density lipoprotein particles, a study has shown.

In the observational study of 670 patients, those having higher levels of HDL particles rich in triglycerides before starting statins were 3-21 times more likely to develop various types of myotoxicity while on these medications.

“These results suggest an association between HDL-triglyceride concentration at baseline and markers of statin intolerance,” lead investigator Dr. Tarek Bouhali said at the annual World Congress on Heart Disease sponsored by the International Academy of Cardiology.

“Right now, we can’t tell what the mechanism is,” he commented. “But ... HDL is a heterogeneous group of lipoproteins and is not only cholesterol,” and in this setting, it appears that heterogeneity may be useful for risk stratification.

Skeletal muscle adverse events are the leading complication of statin therapy, according to Dr. Bouhali. “Muscular side effects are usually mild and reversible; however, knowledge of the underlying mechanism and risk factors is required for prompt identification and proper management for these side effects.”

Furthermore, he noted, understanding and preventing statin adverse effects are important because side effects can lead to both reduced compliance and increased health care costs.

The investigators collected fasting plasma samples from adult French Canadian patients who were about to start lipid-lowering therapy and were receiving care according to American Heart Association guidelines. The samples were ultracentrifuged to determine levels of cholesterol and triglyceride associated with HDL particles.

The study patients were 50 years old on average, and 63% were male. About 12% were taking statins in combination with other lipid-lowering medications (fibrates, bile acid sequestrants, nicotinic acid, or inhibitors of cholesterol absorption).

Overall, 22% of the patients had at least one adverse effect of any type (muscular or nonmuscular), reported Dr. Bouhali of the University of Montreal and the lead investigator with the ECOGENE-21 project.

In terms of the muscular adverse effects, 20% of patients developed myalgia, 7% had a creatine kinase level of 300 U/L or higher, 3% had trace proteinuria or myoglobinuria, and 2% had a creatine kinase level of 500 U/L or higher.

After adjustment for age, sex, statin dose, and concomitant medications, a higher plasma HDL-triglyceride level before starting treatment was associated with a greater risk of myotoxicity, and especially the more severe forms, noted Dr. Bouhali.

Specifically, the log10-transformed HDL-triglyceride level in millimoles per liter was significantly associated with the development of myalgia (odds ratio, 2.9); a creatine kinase level of 300 U/L or higher (OR, 6.0); proteinuria or myoglobinuria (OR, 12.6); and a creatine kinase level of 500 U/L or higher (OR, 20.9).

In addition, a higher HDL-triglyceride level at baseline was associated with a borderline increase in the risk of any (muscular or nonmuscular) adverse effect (OR, 2.5; P = .065).

In contrast, the level of HDL cholesterol was not significantly associated with the likelihood of statin adverse effects.

The study’s findings should be validated and replicated in other populations, said Dr. Bouhali.

In addition, “further mechanistic studies are needed to explore the implication of HDL particle composition in the development of statin intolerance,” he said in comments provided by e-mail.

Dr. Bouhali reported that he had no relevant conflicts of interest.

VANCOUVER, B.C. – Information about a patient’s risk of developing statin-induced myotoxicity may come from a surprising source: the composition of his or her high-density lipoprotein particles, a study has shown.

In the observational study of 670 patients, those having higher levels of HDL particles rich in triglycerides before starting statins were 3-21 times more likely to develop various types of myotoxicity while on these medications.

“These results suggest an association between HDL-triglyceride concentration at baseline and markers of statin intolerance,” lead investigator Dr. Tarek Bouhali said at the annual World Congress on Heart Disease sponsored by the International Academy of Cardiology.

“Right now, we can’t tell what the mechanism is,” he commented. “But ... HDL is a heterogeneous group of lipoproteins and is not only cholesterol,” and in this setting, it appears that heterogeneity may be useful for risk stratification.

Skeletal muscle adverse events are the leading complication of statin therapy, according to Dr. Bouhali. “Muscular side effects are usually mild and reversible; however, knowledge of the underlying mechanism and risk factors is required for prompt identification and proper management for these side effects.”

Furthermore, he noted, understanding and preventing statin adverse effects are important because side effects can lead to both reduced compliance and increased health care costs.

The investigators collected fasting plasma samples from adult French Canadian patients who were about to start lipid-lowering therapy and were receiving care according to American Heart Association guidelines. The samples were ultracentrifuged to determine levels of cholesterol and triglyceride associated with HDL particles.

The study patients were 50 years old on average, and 63% were male. About 12% were taking statins in combination with other lipid-lowering medications (fibrates, bile acid sequestrants, nicotinic acid, or inhibitors of cholesterol absorption).

Overall, 22% of the patients had at least one adverse effect of any type (muscular or nonmuscular), reported Dr. Bouhali of the University of Montreal and the lead investigator with the ECOGENE-21 project.

In terms of the muscular adverse effects, 20% of patients developed myalgia, 7% had a creatine kinase level of 300 U/L or higher, 3% had trace proteinuria or myoglobinuria, and 2% had a creatine kinase level of 500 U/L or higher.

After adjustment for age, sex, statin dose, and concomitant medications, a higher plasma HDL-triglyceride level before starting treatment was associated with a greater risk of myotoxicity, and especially the more severe forms, noted Dr. Bouhali.

Specifically, the log10-transformed HDL-triglyceride level in millimoles per liter was significantly associated with the development of myalgia (odds ratio, 2.9); a creatine kinase level of 300 U/L or higher (OR, 6.0); proteinuria or myoglobinuria (OR, 12.6); and a creatine kinase level of 500 U/L or higher (OR, 20.9).

In addition, a higher HDL-triglyceride level at baseline was associated with a borderline increase in the risk of any (muscular or nonmuscular) adverse effect (OR, 2.5; P = .065).

In contrast, the level of HDL cholesterol was not significantly associated with the likelihood of statin adverse effects.

The study’s findings should be validated and replicated in other populations, said Dr. Bouhali.

In addition, “further mechanistic studies are needed to explore the implication of HDL particle composition in the development of statin intolerance,” he said in comments provided by e-mail.

Dr. Bouhali reported that he had no relevant conflicts of interest.