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Abstract
Objectives: To examine the relationship between plasma lipid measurements and incident ischemic vascular events (ischemic stroke [IS], and as a positive control, myocardial infarction [MI]) in a community cohort.
Methods: In 6,276 stroke-free Framingham participants (aged 64 ± 10 years, 56% female), we related plasma lipid levels (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], and TC/HDL-C ratio) measured at the original cohort 15th (1977–1979) and 20th examination cycles (1986–1990) and (TC, HDL-C, TC/HDL-C ratio, triglycerides [TG], and low-density lipoprotein cholesterol [LDL-C]) measured at the offspring fourth examination (1995–1998), to 10-year risk of incident IS and MI. Utilizing genome-wide genotyping in the same subjects, we used mendelian randomization methods to assess whether observed associations were incidental or causal.
Results: During a mean follow-up of 9 years, 301 participants experienced incident IS. In multivariable-adjusted analyses, HDL-C ≤40 mg/dL and TC/HDL ratio ≥5 were associated with increased risk of IS (hazard ratio [95% confidence interval]: 1.59 [1.23–2.05], p < 0.001 and 1.47 [1.15–1.87], p < 0.001), but not TC or LDL-C. In adjusted analysis, a strong association between TG and IS was diminished. In the MI-free sample (n = 5,875, aged 64 ± 10 years, 58% female; 403 MI events), all lipid markers were associated with MI risk. A genetic risk score comprising 47 known determinants of circulating HDL-C was not associated with IS.
Conclusions: In a middle-aged to elderly community sample, we observed that low HDL-C and high TC/HDL-C ratio, but not LDL-C or TG were associated with risk of incident IS. We observed the usual associations between lipids and risk of MI. Our findings suggest an important, but less likely causal, role of HDL-C over other lipid biomarkers for optimal stroke risk stratification.
GLOSSARY
- ABI=
- atherothrombotic brain infarct;
- CI=
- confidence interval;
- CVD=
- cardiovascular disease;
- FHS=
- Framingham Heart Study;
- FSRP=
- Framingham Stroke Risk Profile;
- HDL-C=
- high-density lipoprotein cholesterol;
- HR=
- hazard ratio;
- IS=
- ischemic stroke;
- LDL-C=
- low-density lipoprotein cholesterol;
- MI=
- myocardial infarction;
- SNP=
- single nucleotide polymorphism;
- TC=
- total cholesterol;
- TG=
- triglycerides;
- WHS=
- Women's Health Study
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received March 31, 2014.
- Accepted in final form October 8, 2014.
- © 2015 American Academy of Neurology
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