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Research Article | Open Access

Cholesterol paradox in the community-living old adults: is higher better?

Sheng-Shu WANG1,*, Shan-Shan YANG2,*, Chun-Jiang PAN3,*, Jian-Hua WANG1, Hao-Wei LI1, Shi-Min CHEN1, Jun-Kai HAO4, Xue-Hang LI1, Rong-Rong LI1, Bo-Yan LI1, Jun-Han YANG1, Yue-Ting SHI1, Huai-Hao LI1, Ying-Hui BAO1, Wen-Chang WANG1, Sheng-Yan DU1, Yao HE1,5(), Chun-Lin LI6(), Miao LIU7()
Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, the Second Medical Center, Chinese PLA General Hospital, Beijing, China
Department of Disease Prevention and Control, the First Medical Center, Chinese PLA General Hospital, Beijing, China
Department of Disease Control and Prevention, Chinese PLA Strategic Support Force Characteristic Medical Center, Beijing, China
Department of Health Service, the Second Medical Center, Chinese PLA General Hospital, Beijing, China
Department of Epidemiology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China
Institute of Endocrinology, the Second Medical Center, Chinese PLA General Hospital, Beijing, China
Department of anti-NBC Medicine, Chinese PLA Medical School, Chinese PLA General Hospital, Beijing, China

*The authors contributed equally to this manuscript

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Abstract

OBJECTIVE

To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.

METHODS

A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators.

RESULTS

A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%–4.43%) and 14.83% (95% CI: 13.79%–15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730–0.997), LDL-C (HR = 0.817, 95% CI: 0.680–0.982) and HDL-C (HR = 0.443, 95% CI: 0.271–0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501–0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010–1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death.

CONCLUSIONS

In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

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Journal of Geriatric Cardiology
Volume 20 Issue 12,
December 2023
Pages 837-844
DOI: 10.26599/1671-5411.2023.12.003
Cite this article:
WANG S-S, YANG S-S, PAN C-J, et al. Cholesterol paradox in the community-living old adults: is higher better?. Journal of Geriatric Cardiology, 2023, 20(12): 837-844. https://doi.org/10.26599/1671-5411.2023.12.003
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Baseline remnant cholesterol characteristics of the community-living old adults.

VariablesRemnant cholesterolP-valuePtrend-value
≤ 0.28 mmol/L (n = 1242)0.29–0.52 mmol/L (n = 1152)0.53–0.76 mmol/L (n = 1082)≥ 0.77 mmol/L (n = 1023)
Data are presented as means ± SD or n (%). HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; TC: total cholesterol.
Age, yrs 70.02 ± 6.54 70.93 ± 6.74 70.71 ± 6.85 70.33 ± 6.95 0.0050.331
Uric acid, μmol/L286.41 ± 75.80296.07 ± 82.19303.69 ± 89.42312.40 ± 88.85< 0.001< 0.001
Body mass index, kg/m2 24.03 ± 3.34 24.31 ± 3.42 24.99 ± 3.42 25.08 ± 3.45 < 0.001< 0.001
Systolic blood pressure, mmHg131.86 ± 16.82136.78 ± 18.08138.55 ± 19.92139.43 ± 20.54< 0.001< 0.001
Diastolic blood pressure, mmHg 78.49 ± 11.42 77.75 ± 10.48 78.50 ± 10.51 80.25 ± 11.77< 0.001< 0.001
Fasting plasma glucose, mmol/L 5.91 ± 1.52 5.87 ± 1.47 5.98 ± 1.71 6.33 ± 2.14 < 0.001< 0.001
TC, mmol/L 4.45 ± 0.85 4.78 ± 0.86 5.15 ± 0.91 5.62 ± 1.15 < 0.001< 0.001
Triglyceride, mmol/L 1.09 ± 0.44 1.24 ± 0.45 1.56 ± 0.59 2.42 ± 1.44 < 0.001< 0.001
HDL-C, mmol/L 1.47 ± 0.36 1.48 ± 0.35 1.38 ± 0.33 1.28 ± 0.32 < 0.001< 0.001
LDL-C, mmol/L 2.96 ± 0.84 2.90 ± 0.76 3.14 ± 0.84 3.16 ± 1.03 < 0.001< 0.001
Creatinine, μmol/L 69.41 ± 18.48 72.34 ± 19.48 72.12 ± 20.73 70.63 ± 27.680.0030.165
Area< 0.001< 0.001
　Rural1062 (85.51%)405 (35.16%)373 (34.47%)557 (54.45%)
　Urban180 (14.49%)747 (64.84%)709 (65.53%)466 (45.55%)
Gender< 0.001< 0.001
　Male597 (48.07%)504 (43.75%)405 (37.43%)308 (30.11%)
　Female645 (51.93%)648 (56.25%)677 (62.57%)715 (69.89%)
Ethnic0.3370.471
　Han1225 (98.63%)1126 (97.74%)1058 (97.78%)1005 (98.24%)
　Minority nationality17 (1.37%)26 (2.26%)24 (2.22%)18 (1.76%)
Educational level< 0.001< 0.001
　Primary school and below912 (73.43%)551 (47.83%)538 (49.72%)621 (60.70%)
　Middle school and above330 (26.57%)601 (52.17%)544 (50.28%)402 (39.30%)
Marital status< 0.001< 0.001
　Married153 (12.32%)636 (55.21%)603 (55.73%)382 (37.34%)
　Widowed/Divorced/Single1089 (87.68%)516 (44.79%)479 (44.27%)641 (62.66%)
Smoking< 0.001< 0.001
　Never790 (63.61%)812 (70.49%)764 (70.61%)761 (74.39%)
　Ever167 (13.45%)165 (14.32%)154 (14.23%)108 (10.56%)
　Still285 (22.95%)175 (15.19%)164 (15.16%)154 (15.05%)
Alcohol drinking< 0.001< 0.001
　Never619 (49.84%)766 (66.49%)738 (68.21%)668 (65.30%)
　Ever80 (6.44%)67 (5.82%)56 (5.18%)47 (4.59%)
　Still543 (43.72%)319 (27.69%)288 (26.62%)308 (30.11%)
Exercise< 0.001< 0.001
　No442 (35.59%)222 (19.27%)200 (18.48%)269 (26.30%)
　Yes800 (64.41%)930 (80.73%)882 (81.52%)754 (73.70%)
Hypertension< 0.001< 0.001
　No583 (46.94%)407 (35.33%)345 (31.89%)309 (30.21%)
　Yes659 (53.06%)745 (64.67%)737 (68.11%)714 (69.79%)

Mortality of baseline remnant cholesterol quarters.

DeathRemnant cholesterolTotal (n = 4499)
≤ 0.28 mmol/L (n = 1242)0.29–0.52 mmol/L (n = 1152)0.53–0.76 mmol/L (n = 1082)≥ 0.77 mmol/L (n = 1023)
Cardiovascular disease death
　Number of death cases36454548174
　Mortality, %2.90 (1.96–3.83)3.91 (2.79–5.03)4.16 (2.97–5.35)4.69 (3.39–5.99)3.87 (3.30–4.43)
　Total person-years848910,2819627819936,596
　Death density, per 100 person-years0.42 (0.29–0.56)0.44 (0.31–0.57)0.47 (0.33–0.60)0.59 (0.42–0.75)0.48 (0.41–0.55)
All-cause death
　Number of death cases166174172155667
　Mortality, %13.37 (11.47–15.26)15.10 (13.03–17.18)15.90 (13.71–18.08)15.90 (13.71–18.08)14.83 (13.79–15.86)
　Total person-years848910,2819627819936,596
　Death density, per 100 person-years1.96 (1.66–2.25)1.69 (1.44–1.94)1.79 (1.52–2.05)1.89 (1.60–2.19)1.82 (1.69–1.96)

Associations of baseline lipid levels and CVD death and all-cause death among the community-living old adults.

CVD deathAll-cause death
Model 1Model 2Model 1Model 2
Model 1: not adjusted. Model 2: adjusted for age, gender, body mass index, education, marital status, smoking, alcohol use, exercise, diabetes mellitus, and hypertension. CVD: cardiovascular disease; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; RC: remnant cholesterol; TC: total cholesterol.
TC, mmol/L0.768 (0.659–0.897)0.854 (0.730–0.997)0.823 (0.761–0.889)0.932 (0.861–1.009)
Triglyceride, mmol/L0.998 (0.854–1.166)1.066 (0.909–1.250)0.899 (0.821–0.986)1.005 (0.918–1.099)
LDL-C, mmol/L0.729 (0.608–0.873)0.817 (0.680–0.982)0.833 (0.761–0.912)0.962 (0.878–1.055)
HDL-C, mmol/L0.415 (0.261–0.662)0.443 (0.271–0.724)0.648 (0.517–0.812)0.637 (0.501–0.810)
Non-HDL-C, mmol/L0.846 (0.724–0.989)0.928 (0.793–1.086)0.862 (0.796–0.932)0.979 (0.904–1.061)
RC, mmol/L1.227 (0.985–1.529)1.276 (1.010–1.613)0.952 (0.809–1.120)1.032 (0.882–1.206)

Associations of baseline dyslipidemia and CVD death and all-cause death among the community-living old adults.

CVD deathAll-cause death
Model 1Model 2Model 1Model 2
Model 1: not adjusted. Model 2: adjusted for age, gender, body mass index, education, marital status, smoking, alcohol use, exercise, diabetes mellitus, and hypertension. CVD: cardiovascular disease; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; RC: remnant cholesterol; TC: total cholesterol.
TC ≥ 6.20 mmol/L0.876 (0.564–1.360)0.986 (0.630–1.542)0.798 (0.630–1.009)0.939 (0.739–1.193)
Triglyceride ≥ 2.30 mmol/L0.979 (0.650–1.477)1.121 (0.731–1.721)0.879 (0.706–1.095)1.065 (0.847–1.338)
LDL-C ≥ 4.10 mmol/L0.717 (0.434–1.183)0.813 (0.491–1.347)0.820 (0.642–1.048)0.983 (0.767–1.259)
HDL-C < 1.00 mmol/L1.539 (1.007–2.351)1.362 (0.879–2.111)1.359 (1.083–1.707)1.287 (1.017–1.628)
Non-HDL-C ≥ 4.90 mmol/L0.918 (0.569–1.480)1.004 (0.618–1.630)0.834 (0.646–1.078)0.977 (0.753–1.268)
RC ≥ 0.80 mmol/L1.378 (0.979–1.939)1.422 (1.001–2.020)1.042 (0.863–1.258)1.104 (0.911–1.339)

Associations of baseline lipid levels and CVD death in non-dyslipidemia and dyslipidemia groups based on the physiological reference values of indicators.

Non-dyslipidemia groupDyslipidemia group
HR95% CIHR95% CI
The indicators in both non-dyslipidemia and dyslipidemia groups adjusted for age, gender, body mass index, education, marital status, smoking, alcohol use, exercise, diabetes mellitus, and hypertension. CVD: cardiovascular disease; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; RC: remnant cholesterol; TC: total cholesterol.
TC0.7330.538–0.9990.8590.712–1.037
Triglyceride1.3590.796–2.3211.0090.828–1.231
LDL-C0.8470.597–1.2020.7810.627–0.974
HDL-C0.5040.265–0.9570.4450.268–0.740
Non-HDL-C0.8630.621–1.1980.9060.743–1.105
RC0.8150.283–2.3461.3091.006–1.703