In the JournalsPerspective

Low LDL, triglycerides increase stroke risk in women

Women with LDL levels below 70 mg/dL and low triglyceride levels had increased risk for hemorrhagic stroke, according to a study published in Neurology.

“Strategies to lower cholesterol and triglyceride levels, like modifying diet or taking statins, are widely used to prevent cardiovascular disease, but our large study shows that in women, very low levels may also carry some risks,” Pamela M. Rist, ScD, assistant professor in the division of preventive medicine at Brigham and Women’s Hospital and Harvard Medical School, said in a press release. “Women already have a higher risk of stroke than men, in part because they live longer, so clearly defining ways to reduce their risk is important.”

Women’s Health Study

Researchers analyzed data from 27,937 patients from the Women’s Health Study. Blood samples were taken to measure LDL, HDL, total cholesterol and triglycerides. Women were then categorized by LDL: < 70 mg/dL (n = 1,069; mean age, 53 years), 70 mg/dL to 99.9 mg/dL (n = 5,739; mean age, 53 years), 100 mg/dL to 129.9 mg/dL (n = 10,067; mean age, 54 years), 130 mg/dL to 159.9 mg/dL (n = 7,187; mean age, 56 years) and 160 mg/dL (n = 3,875; mean age, 57 years).

Questionnaires were completely annually to collect information on outcomes including stroke. Follow-up was conducted until the first stroke event, loss to follow-up or study completion, whichever occurred first for a mean of 19.3 years.

There were 137 incident hemorrhagic strokes during follow-up. Compared with women with LDL levels between 100 mg/dL and 129.9 mg/dL, those with levels less than 70 mg/dL had 2.17 times the risk for a hemorrhagic stroke after multivariable adjustment (95% CI, 1.05-4.48). Women with LDL levels greater than 160 mg/dL had an elevated risk for hemorrhagic stroke, although it was not statistically significant (RR = 1.53; 95% CI, 0.92-2.52). An increased risk for hemorrhagic stroke was not seen in women with LDL levels between 70 mg/dL and 99.9 mg/dL (RR = 1.25; 95% CI, 0.76-2.04) or between 130 mg/dL and 159.9 mg/dL (RR = 1.14; 95% CI, 0.72-1.8).

Low triglyceride levels

A significantly increased risk for hemorrhagic stroke was seen in women in the lowest quartile of triglycerides vs. those in the top quartile after multivariable adjustment (RR = 2; 95% CI, 1.18-3.39).

No significant associations were observed between total cholesterol or HDL and the risk for hemorrhagic stroke.

“Women with very low LDL-C or low triglycerides should be monitored for other modifiable risk factors for hemorrhagic stroke, for example, hypertension and smoking, to help reduce their overall risk of experiencing a hemorrhagic stroke event,” Rist and colleagues wrote. “Additional targeted research is needed to determine if our finding of elevated LDL-C levels ( 160 mg/dL) being associated with an increased risk of hemorrhagic stroke can be replicated in other cohorts and to provide insights on how to reduce hemorrhagic stroke risk in these individuals.” – by Darlene Dobkowski

Disclosure s : The authors report no relevant financial disclosures.

Women with LDL levels below 70 mg/dL and low triglyceride levels had increased risk for hemorrhagic stroke, according to a study published in Neurology.

“Strategies to lower cholesterol and triglyceride levels, like modifying diet or taking statins, are widely used to prevent cardiovascular disease, but our large study shows that in women, very low levels may also carry some risks,” Pamela M. Rist, ScD, assistant professor in the division of preventive medicine at Brigham and Women’s Hospital and Harvard Medical School, said in a press release. “Women already have a higher risk of stroke than men, in part because they live longer, so clearly defining ways to reduce their risk is important.”

Women’s Health Study

Researchers analyzed data from 27,937 patients from the Women’s Health Study. Blood samples were taken to measure LDL, HDL, total cholesterol and triglycerides. Women were then categorized by LDL: < 70 mg/dL (n = 1,069; mean age, 53 years), 70 mg/dL to 99.9 mg/dL (n = 5,739; mean age, 53 years), 100 mg/dL to 129.9 mg/dL (n = 10,067; mean age, 54 years), 130 mg/dL to 159.9 mg/dL (n = 7,187; mean age, 56 years) and 160 mg/dL (n = 3,875; mean age, 57 years).

Questionnaires were completely annually to collect information on outcomes including stroke. Follow-up was conducted until the first stroke event, loss to follow-up or study completion, whichever occurred first for a mean of 19.3 years.

There were 137 incident hemorrhagic strokes during follow-up. Compared with women with LDL levels between 100 mg/dL and 129.9 mg/dL, those with levels less than 70 mg/dL had 2.17 times the risk for a hemorrhagic stroke after multivariable adjustment (95% CI, 1.05-4.48). Women with LDL levels greater than 160 mg/dL had an elevated risk for hemorrhagic stroke, although it was not statistically significant (RR = 1.53; 95% CI, 0.92-2.52). An increased risk for hemorrhagic stroke was not seen in women with LDL levels between 70 mg/dL and 99.9 mg/dL (RR = 1.25; 95% CI, 0.76-2.04) or between 130 mg/dL and 159.9 mg/dL (RR = 1.14; 95% CI, 0.72-1.8).

Low triglyceride levels

A significantly increased risk for hemorrhagic stroke was seen in women in the lowest quartile of triglycerides vs. those in the top quartile after multivariable adjustment (RR = 2; 95% CI, 1.18-3.39).

No significant associations were observed between total cholesterol or HDL and the risk for hemorrhagic stroke.

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“Women with very low LDL-C or low triglycerides should be monitored for other modifiable risk factors for hemorrhagic stroke, for example, hypertension and smoking, to help reduce their overall risk of experiencing a hemorrhagic stroke event,” Rist and colleagues wrote. “Additional targeted research is needed to determine if our finding of elevated LDL-C levels ( 160 mg/dL) being associated with an increased risk of hemorrhagic stroke can be replicated in other cohorts and to provide insights on how to reduce hemorrhagic stroke risk in these individuals.” – by Darlene Dobkowski

Disclosure s : The authors report no relevant financial disclosures.

    Perspective
    Gina Lundberg

    Gina Lundberg

    This study needs to be very closely looked at and cautiously interpreted. In general, lower LDL and low triglyceride levels are associated with reduced CV risks and improved outcomes and yet, previous studies have also shown that elevated total cholesterol was inversely associated with hemorrhagic stroke.

    This is a very large study with nearly 20 years of follow-up, so it is clearly an important study for women. The group of women who had LDL under 70 mg/dL had the lowest numbers of women in the study, had more women in the high alcohol intake category, had the lowest use of cholesterol-lowering medications, had more women in the underweight group and had many women with diabetes. These potential confounding factors make the results less reliable since these behaviors and chronic diseases are important risks for hemorrhagic stroke.

    Women with migraine headache with aura, woman with a past history of preeclampsia and women who take aspirin also have been shown to have increased risk for hemorrhagic stroke. I do not believe these risks were included in the study.

    Most clinicians are encouraging patients to lose weight, eat healthier, exercise, reduce blood cholesterol, reduce blood sugar and reduce BP. These things are the foundation for our new primary prevention guidelines. I rarely see a patient with an LDL so low that I am concerned that the low cholesterol could increase their risk for a CV event.

    Risk of hemorrhagic stroke in women is associated with hypertension, pregnancy complications and other known CV risk factors. The number of hemorrhagic strokes in the total population was quite low but still concerning because the mortality is higher with hemorrhagic stroke than ischemic stroke. We need to find more ways to prevent all strokes.

    We definitely need more studies looking at women with low LDL that take into account newer sex-specific risk factors such as pregnancy complications, inflammation, migraine with aura, thrombotic and vascular issues as well as lifestyle information.

    A previous study on social determinants of health showed that 80% of hemorrhagic strokes were seen in low- and middle-income groups. Looking at these factors could also be very important.

    • Gina Lundberg, MD, FACC, FAHA
    • Clinical Director, Emory Women’s Heart Center
      Associate Professor of Medicine
      Emory University School of Medicine, Atlanta

    Disclosures: Lundberg reports no relevant financial disclosures.