Total cholesterol and stroke mortality in middle-aged and elderly adults: A prospective cohort study

  • Sang-Wook Yi
    Corresponding author. Department of Preventive Medicine and Public Health, College of Medicine, Catholic Kwandong University, Bumil-ro 579, Gangneung, Gangwon-do, 25601, Republic of Korea.
    Department of Preventive Medicine and Public Health, Catholic Kwandong University College of Medicine, Gangneung, 25601, Republic of Korea

    Institute for Clinical and Translational Research, Catholic Kwandong University International St. Mary's Hospital, Incheon, 22711, Republic of Korea
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  • Dae-Hee Shin
    Cardiovascular center, Catholic Kwandong University College of Medicine, International St. Mary's Hospital, Incheon, 22711, Republic of Korea
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  • Hyeyun Kim
    Department of Neurology, Catholic Kwandong University College of Medicine, International St. Mary's Hospital, Incheon, 22711, Republic of Korea
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  • Jee-Jeon Yi
    Institute for Occupational and Environmental Health, Catholic Kwandong University, Gangneung, 25601, Republic of Korea
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  • Heechoul Ohrr
    Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
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      • Total stroke mortality shows U-curve associations with total cholesterol (TC).
      • Ischemic stroke have a positive association for TC.
      • Intracerebral hemorrhage has no inverse associations with TC in the range ≥200 mg/dL.
      • High TC levels increase ischemic stroke mortality in middle-aged and elderly persons.


      Background and aims

      The association between cholesterol and stroke has been inconsistent. This study aimed to examine the association between total cholesterol (TC) and mortality from total stroke and stroke subtypes.


      503,340 Korean adults aged 40–80 years without a history of heart disease or stroke participated in routine health examinations in 2002 and 2003, and were followed up until 2013. Adjusted hazard ratios (HRs) for stroke (I60-I69) mortality were calculated.


      Nonlinear associations for total stroke (U-curve) and hemorrhagic stroke (L-curve), especially intracerebral hemorrhage (ICH), but a linear association for ischemic stroke, were found. In the range <200 mg/dL, TC was inversely associated with stroke mortality (HR per 39 mg/dL [1 mmol/L] increase = 0.88 [95% CI = 0.80–0.95]), mainly due to hemorrhagic stroke (HR = 0.78 [0.68–0.90]), especially ICH (HR = 0.72 [0.62–0.85]). In the upper range (200–349 mg/dL), TC was positively associated with stroke mortality (HR = 1.09 [1.01–1.16]); ICH and subarachnoid hemorrhage mortality showed no inverse association. The associations were generally similar in middle-aged (40–64 years) and elderly (≥65 years) adults and, in the upper range, each 1 mmol/L (39 mg/dL) higher TC was associated with 11% higher mortality from stroke (95% CI = 2%–21%) in the elderly. Both middle-aged (39%) and elderly (23%) adults had higher ischemic stroke mortality associated with TC ≥240 mg/dL, compare to <200 mg/dL.


      TC level around 200 mg/dL was associated with the lowest risk of overall stroke in the elderly and middle-aged adults. No stroke subtype including ICH, was inversely associated with TC in the range ≥200 mg/dL.


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      Linked Article

      • Strokes, cholesterol and statins: When mortality is an endpoint
        AtherosclerosisVol. 275
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          The Yi et al. stroke mortality study, with 5.2 million person-years of observation in a representative Korean population cohort with a single baseline total cholesterol (TC) measurement, highlights several important issues [1]. First, the authors note the fact that cholesterol lowering “particularly by statins” does not lower stroke mortality in randomized trials. Second, the fact that 53% of stroke deaths were from hemorrhagic strokes, far surpassing its incidence of about 10–20% in all strokes in many countries [1], and that are mainly nonfatal ischemic strokes.
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      • Reply to: “Strokes, cholesterol and statins: When mortality is an endpoint”
        AtherosclerosisVol. 275
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          The authors generally concur with Dr. Vos and Dr. Biron [1] that long-term low cholesterol levels caused by long-term statin use might be a concern, when overall mortality or survival, is an end-point, since many prospective cohort studies have shown that a low cholesterol levels was associated with higher mortality [2–4], and the effects of the long-term cholesterol lowering treatment have not been sufficiently investigated [5]. Clinical trials, mainly performed in men with a high risk of heart disease, have shown that statin therapy reduces all-cause mortality, almost entirely by reducing heart disease mortality, during the follow-up period of clinical trials.
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