2024 Volume 31 Issue 5 Pages 587-602
Aim: Studies on the relationship between remnant cholesterol (RC) and arterial stiffness (AS) are limited. This study aims to investigate the relationship between RC and AS and to explore RC, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), non-HDL-C, LDL-C/HDL-C, TG/HDL-C, lipoprotein combine index (LCI), and TC/HDL-C, which are lipid parameters most strongly associated with AS.
Methods: A total of 4653 participants from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals) study were recruited. AS was defined as a brachial–ankle pulse wave velocity of ≥ 1400 cm/s. Multiple logistic regression analyses were performed to detect its association with lipid parameters (RC, TG, TC, HDL-C, LDL-C, non-HDL-C, LDL-C/HDL-C, TG/HDL-C, LCI, and TC/HDL-C).
Results: Logistic regression analysis showed that compared with other traditional or non-traditional lipid parameters, the association between RC and AS was the strongest (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.30–1.95, P＜0.001). In the stratified analysis, RC was significantly associated with AS in both sexes and at any age, as well as blood glucose, blood pressure, and body mass index levels. Besides, RC and AS were still significantly associated when TG＜1.7 mmol/L (OR:1.58, 95% CI: 1.02–2.45, P=0.04), LDL-C ＜3.4 mmol/L (OR:1.32, 95% CI: 1.01–1.73, P=0.041), HDL-C ≥ 1.0 mmol/L (OR:1.67, 95% CI: 1.34–2.08, P＜0.001), or non-HDL-C＜4.1 mmol/L (OR: 1.42, 95% CI: 1.10-1.82, P=0.007) are controlled within the appropriate range.
Conclusion: In conclusion, compared with traditional lipids and lipid ratios, RC is more strongly associated with AS. The association between RC and AS remains significant even when TG, LDL-C, HDL-C, or non-HDL-C levels are controlled within the appropriate range.
Key messages: This is the first multicenter, large-sample study of the relationship between remnant cholesterol (RC) and arterial stiffness (AS). RC is more strongly associated with AS than traditional lipids and lipid ratios. The association between RC and AS remains significant even when traditional lipid levels are controlled within the appropriate range.
Cardiovascular disease (CVD) is currently one of the major causes of death globally; it poses severe public health challenges and imposes economic burdens on patients1). In 2017, CVD was the cause of 17.9 million deaths around the world, accounting for 31.8% of all deaths2). Hence, effective measures to prevent CVD are urgently needed. The development of CVD is a continuous process, and arterial stiffness (AS) is an essential intermediate stage in this course3). However, as a chronic disease, AS could be symptomless even for decades4).
The “gold standard” for AS is carotid–femoral pulse wave velocity (cfPWV)5), but some of its disadvantages include long measurement time, examiner variations, and the inconvenience of an exposed femoral site6). Alternatively, brachial–ankle pulse wave velocity (baPWV), a credible predictor of vascular injury and AS7) could evaluate the level of AS in a convenient, reproducible, and non-invasive approach. baPWV is highly correlated with cfPWV, especially in Asian populations8). Nevertheless, pulse wave velocity (PWV) testing is not widely available in primary community care facilities, especially in rural areas of China9), so methods of AS assessment are still very limited. AS is a tissue symbol of subclinical atherosclerosis, and the identification of risk factors highly associated with AS or PWV might offer vital clinical benefits prior to the occurrence and development of clinical atherosclerosis.
Dyslipidemia is thought to be one potential risk factor for AS10). Many previous studies have focused on the relationship between traditional lipids and their ratios and AS, but the results of these studies are inconsistent. However, studies on the association between remnant cholesterol (RC) and AS are limited11, 12), although basic experiments have shown that RC is pro-inflammatory and promotes the generation and progression of atherosclerosis through adhesion13). RC refers to the metabolic residues of triglyceride-rich lipoproteins (TGRLs), that is, the metabolic residues of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and chylomicron when not fasting, and the metabolic residues of VLDL and IDL when fasting14). Previous epidemiological studies have shown that TGRL and its residues are substantial determinants of CVD risk12, 15). One large-scale clinical experiment revealed that intensive lipid-lowering treatment in participants with higher RC reduced the CVD risk16). Therefore, the objectives of the current study were to investigate the relationship between RC and AS reflected by elevated baPWV, and to explore RC, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, TG/HDL-C, LDL-C/HDL-C, TC/HDL-C, and lipoprotein combine index (LCI), which are lipid parameters most strongly associated with AS.
The participants for the current study were collected from the Beijing subcenter of the REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study17). All participants provided informed consent. The protocol of this study was approved by the Committee on Human Research of the Chinese People’s Liberation Army General Hospital. From April to October 2015, a total of 10,276 long-lived Beijing residents over the age of 40 were recruited. After excluding participants with missing important data, those with a previous diagnosis of cancer, viral hepatitis, cirrhosis, or chronic renal failure, as well as those using lipid-lowering drugs within 30 days, with an ankle–brachial index of ≤ 0.9, who have suffered from CVD, who have used antihypertensive drugs within 30 days, and with a calculated RC of ＜0, a total of 4653 participants were enrolled.
Data CollectionTrained epidemiologists assisted participants in completing the questionnaire, which included but was not limited to past diagnoses, medication use in the last 30 days, family history of CVD, level of daily physical activity, smoking habits, alcohol consumption, and occupation.
All participants underwent physical examination, which included height, weight, waist circumference (WC), hip circumference (HC), and neck circumference. All measurements were taken using the same measuring device and scale. During the measurements, the participants removed their shoes, hats, and heavy coats and stood in an upright position on a wooden platform.
After sitting still for 5 minutes, participants’ blood pressure was measured 3 times at least 1 minute apart using an Omron electronic sphygmomanometer, and the mean values were calculated for inclusion in the study.
The participants fasted for 8–10 hours the night before the test, and participants without or with diabetes were tested for 75 g oral glucose tolerance or 100 g steamed-bread meal respectively in the early morning. Fasting blood glucose (FBG) and postprandial blood glucose (PBG) were measured using the glucose oxidase method, and glycated hemoglobin (HbA1C) was measured using high-performance liquid chromatography.
Fasting venous blood samples were collected, and TG, TC, HDL-C, LDL-C, aspartate transferase (AST), alanine transferase (ALT), glutamine transferase (GGT), serum creatinine (SCr), and other biochemical indexes were measured using the Abbott automatic C16000 biochemical analyzer.
Trained staff measured baPWV using Omron’s automated arteriosclerosis diagnostic device (BP203RPE-II(VP-1000)). After the participants were asked to lie in a calm position for 3 minutes, the cuff was tied at 2 cm above the brachial artery of both the upper arms and the medial malleolus of both lower limbs. baPWV values on both sides were automatically measured, and the maximum values on both sides were included in the analysis.
Calculation and Definition of VariablesThe nontraditional lipid parameters were calculated using the following formula: RC=TC−LDL-C−HDL-C13), non-HDL‑C=TC−HDL-C18), LCI=TC×TG×LDL-C/HDL-C11). TG/HDL-C, LDL-C/HDL-C, and TC/HDL-C were obtained by the corresponding traditional lipids division.
The following formulas were also used:
Body mass index (BMI) (kg/m2)=weight (Kg)/ (height (m))2
Waist-to-hip ratio (WHR)=WC (cm)/HC (cm)
Estimated glomerular filtration rate (eGFR) (mL/min per 1.73 m2)=175×(SCr in mg/dL)−1.154×age −0.203×(0.742 for women)×(1.212 if African–American)
Because there is no uniform standard for abnormal values of RC and lipid ratios, all independent variables were divided into four groups according to quartiles concerning previous studies6, 19-22). The four groups for RC, non-HDL‑C, LCI, TG/HDL-C, LDL-C/HDL-C, TC/HDL-C, TG, TC, and LDL-C were: Q1 (＜25%, the control group), Q2 (25%–50%), Q3 (50%–75%), and Q4 (≥ 75%). For HDL-C, the four groups were Q4 (≥ 75%, the control group), Q3 (50%–75%), Q2 (25%–50%), and Q1(＜25%). In contrast to other lipids, elevated HDL-C has anti-atherogenic properties23). AS was defined as a baPWV of ≥ 1400 cm/s24, 25).
Exercise habits were defined according to frequency per week (≤ 2 or ≥ 3 times/week, with the latter indicating that the individual was physically active)26). Diabetes was defined according to the criteria from the American Diabetes Association: FBG ≥ 7.0 mmol/L, or PBG ≥ 11.1 mmol/L, or HbA1c ≥ 6.5%, or self-reported diabetes27). Hypertension was defined as a systolic blood pressure (SBP) of ≥ 140 mmHg or a diastolic blood pressure (DBP) of ≥ 90 mmHg.
Statistical AnalysisSPSS 24.0 (IBM, Chicago, Illinois) was used for the statistical analysis. Continuous variables were expressed as mean±standard deviation (SD) for normally distributed variables or as medians (interquartile range) for non-normally distributed variables. Categorical variables were presented numerically (proportionally). The Kruskal–Wallis test was used to test the difference between continuous variables, and categorical variables were analyzed using the chi-square test. Logistic regression was used to test the association between independent variables and AS, and five models were built. Adjustment variables were tested using collinearity diagnosis: a variance inflation factor of ≥ 5 indicated a collinearity problem. The variables included in the adjustment model have the following criteria: (1) there was a significant difference between the baPWV ＜1400 group and the baPWV ≥ 1400 group (P＜0.05) or considered to be associated with AS in clinical practice, and (2) there was no collinearity. Finally, Model 1 was adjusted for age and sex; Model 2 was adjusted for a family history of coronary heart disease and stroke, use of glucose-lowering drugs within 30 days, use of insulin within 30 days, exercise habits, occupation, smoking and drinking habits, BMI, WHR, and neck circumference; Model 3 was adjusted for ALT, AST, GGT, and eGFR; Model 4 was adjusted for SBP and DBP; and Model 5 was adjusted for FBG, PBG, and HbA1c.
After controlling confounders in Model 5, the association between independent variables and AS was explored within the sex, age, BMI, blood pressure, and blood glucose subgroups. Besides, according to the appropriate levels of LDL-C, HDL-C, non-HDL-C, and TG recommended by the 2016 edition of the guidelines for the management of dyslipidemia in Chinese adults, the association between RC and AS was also explored for LDL-C ＜3.4 mmol/L, HDL-C ≥ 1.0 mmol/L, non-HDL-C ＜4.1 mmol/L and TG ＜1.7 mmol/L.
In the sensitivity analysis, we corrected for confounders in Model 5 and TG, TC, HDL-C, and LDL-C to assess the correlation between RC and AS. In addition, we further defined AS as a baPWV of the ≥ 75th percentile (1592 m/s in the present study) and corrected for confounders in Model 5 to assess the association between lipid parameters and the ≥ 75th percentile baPWV.
All statistical tests were two-sided, and P＜0.05 was considered statistically significant.
The study included 4635 participants (Table 1), of whom 2362 had a baPWV of ≥ 1400 and 2291 had a baPWV of ＜1400. Participants whose baPWV was ≥ 1400 were older, had greater TC, LDL-C, RC, non-HDL-C, TG/HDL-C, LDL-C/HDL-C, TC/HDL-C, and LCI; lower HDL-C concentrations; higher BMI, WHR, neck circumference, ALT, AST, GGT, FBG, PBG, HbA1c, SBP, and DBP; lower eGFR; and had a higher percentage of males, were frequent drinkers and smokers, and were more likely to have a family history of stroke and coronary heart disease. People with higher RC levels (the ≥ 75% group of RC) had higher TC, LDL-C, non-HDL-C, TG/HDL-C, LDL-C/HDL-C, TC/HDL-C, and LCI concentrations; lower HDL-C concentrations; had higher BMI, WHR, neck circumference, ALT, AST, GGT, FBG, PBG, HbA1c, SBP, and DBP; lower eGFR; had a higher percentage of males and frequent drinkers and smokers.
| Variable | Total | Two categories of baPWV | P value | 75% two categories of RC | P value | ||
|---|---|---|---|---|---|---|---|
| baPWV ＜1400m/s | baPWV ≥ 1400 m/s | RC ＜0.45 mmol/L | RC ≥ 0.45 mmol/L | ||||
| Number | 4653 | 2291 | 2362 | 3482 | 1175 | ||
| Age, years | 58.91±7.22 | 56.53±6.32 | 61.22±7.30 | ＜0.001 | 59.05±7.37 | 58.48±6.76 | 0.093 |
| Sex, (%) | ＜0.001 | 0.008 | |||||
| Male | 1601 (34.4) | 691 (30.2) | 914 (38.7) | 1167 (33.5) | 440 (37.4) | ||
| Female | 3056 (65.6) | 1600 (69.8) | 1448 (61.3) | 2315 (66.5) | 735 (62.6) | ||
| TC, mmol/L | 5.01 (4.41, 5.60) | 4.95 (4.37, 5.51) | 5.06 (4.47, 5.67) | ＜0.001 | 4.90 (4.34, 5.46) | 5.32 (4.72, 5.92) | ＜0.001 |
| HDL-C, mmol/L | 1.39 (1.17, 1.63) | 1.41 (1.19, 1.66) | 1.36 (1.16, 1.60) | ＜0.001 | 1.48 (1.28, 1.71) | 1.13 (0.99, 1.30) | ＜0.001 |
| LDL-C, mmol/L | 3.23 (2.73, 3.74) | 3.19 (2.70, 3.70) | 3.28 (2.76, 3.80) | 0.001 | 3.18 (2.70, 3.68) | 3.43 (2.8, 3.97) | ＜0.001 |
| TG, mmol/L | 1.36 (1.01, 1.90) | 1.28 (0.95, 1.76) | 1.44 (1.06, 2.03) | ＜0.001 | 1.18 (0.92, 1.47) | 2.41 (1.99, 3.17) | ＜0.001 |
| RC, mmol/L | 0.28 (0.15, 0.45) | 0.25 (0.14, 0.42) | 0.30 (0.18, 0.49) | ＜0.001 | 0.21 (0.12, 0.31) | 0.62 (0.52, 0.84) | ＜0.001 |
| Non-HDL-C, mmol/L | 3.56 (3.03, 4.15) | 3.48 (2.96, 4.04) | 3.65 (3.08, 4.24) | ＜0.001 | 3.39 (2.89, 3.92) | 4.16 (3.63, 4.70) | ＜0.001 |
| TG/HDL-C | 0.96 (0.65, 1.53) | 0.88 (0.61, 1.38) | 1.04 (0.71, 1.65) | ＜0.001 | 0.79 (0.59, 1.09) | 2.11 (1.61, 3.04) | ＜0.001 |
| LDL-C/HDL-C | 2.34 (1.89, 2.85) | 2.27 (1.83, 2.78) | 2.40 (1.94, 2.91) | ＜0.001 | 2.17 (1.77, 2.58) | 2.95 (2.51, 3.41) | ＜0.001 |
| TC/HDL-C | 3.56 (3.02, 4.25) | 3.47 (2.95, 4.12) | 3.68 (3.09, 4.36) | ＜0.001 | 3.32 (2.86, 3.79) | 4.62 (4.12, 5.22) | ＜0.001 |
| LCI | 15.79 (9.30, 27.54) | 14.38 (8.53, 24.05) | 17.53 (10.18, 30.68) | ＜0.001 | 12.42 (7.94, 18.43) | 38.23 (27.92, 54.17) | ＜0.001 |
| BMI, Kg/m2 | 25.09±3.33 | 25.00±3.34 | 25.18±3.32 | 0.017 | 24.74±3.29 | 26.14±3.23 | ＜0.001 |
| Neck circumference, cm | 35.00 (33.00, 37.00) | 34.00 (32.80, 37.00) | 35.00 (33.00, 37.50) | ＜0.001 | 34.50 (33.00, 37.00) | 35.00 (33.60, 38.00) | ＜0.001 |
| WHR | 0.88±0.074 | 0.86±0.063 | 0.89±0.081 | ＜0.001 | 0.87±0.72 | 0.90±0.77 | ＜0.001 |
| ALT, U/L | 16.90 (13.10, 23.10) | 16.30 (12.70, 22.00) | 17.40 (13.50, 24.10) | ＜0.001 | 16.20 (12.60, 21.73) | 19.50 (14.70, 26.90) | ＜0.001 |
| AST, U/L | 18.90 (16.30, 22.20) | 18.40 (15.90, 21.70) | 19.40 (16.70, 22.60) | ＜0.001 | 18.80 (16.20, 22.00) | 19.30 (16.70, 23.00) | ＜0.001 |
| GGT, U/L | 20.30 (15.00, 29.40) | 19.10 (14.30, 27.40) | 21.60 (16.00, 31.10) | ＜0.001 | 18.95 (14.20, 26.90) | 25.30 (18.70, 36.80) | ＜0.001 |
| FBG, mmol/L | 5.22 (4.89, 5.77) | 5.12 (4.82, 5.54) | 5.37 (4.99, 6.07) | ＜0.001 | 5.17 (4.85, 5.67) | 5.40 (5.01, 6.15) | ＜0.001 |
| PBG, mmol/L | 7.51 (6.20, 9.78) | 7.06 (5.92, 8.69) | 8.05 (6.51, 10.89) | ＜0.001 | 7.29 (6.06, 9.36) | 8.19 (6.72, 10.84) | ＜0.001 |
| HbA1c, % | 5.98±0.95 | 5.83±0.76 | 6.13±1.08 | ＜0.001 | 5.93±0.90 | 6.13±1.05 | ＜0.001 |
| SBP, mmHg | 127.17±15.86 | 120.5±13.38 | 133.49±15.52 | ＜0.001 | 126.12±15.83 | 130.29±15.54 | ＜0.001 |
| DBP, mmHg | 76.96±9.35 | 74.86±8.64 | 78.99±9.55 | ＜0.001 | 76.13±9.27 | 79.42±9.13 | ＜0.001 |
| eGFR, mL/ (min·1.73 m2) | 86.69 (77.54, 97.18) | 88.19 (78.99, 98.33) | 85.48 (76.17, 95.60) | ＜0.001 | 87.01 (77.92, 97.28) | 85.87 (76.59, 96.43) | 0.014 |
| Drinking, n (%) | ＜0.001 | 0.005 | |||||
| Never | 3321 (71.3) | 1644 (71.8) | 1675 (70.9) | 2525 (72.5) | 796 (67.7) | ||
| Occasional | 747 (16.0) | 401 (17.5) | 345 (14.6) | 542 (15.6) | 205 (17.4) | ||
| Frequently | 589 (12.6) | 246 (10.7) | 342 (14.5) | 415 (11.9) | 174 (14.8) | ||
| Smoking, n (%) | ＜0.001 | ＜0.001 | |||||
| Never | 3766 (80.9) | 1877 (81.9) | 1886 (79.8) | 2885 (82.9) | 881 (75.0) | ||
| Occasional | 83 (1.8) | 43 (1.9) | 40 (1.7) | 53 (1.5) | 30 (2.6) | ||
| Frequently | 808 (17.4) | 371 (16.2) | 436 (18.5) | 544 (15.6) | 264 (22.5) | ||
| Regular exercise, n (%) | ＜0.001 | 0.003 | |||||
| Yes | 3591 (77.1) | 1709 (74.6) | 1880 (79.6) | 2722 (78.2) | 869 (74.0) | ||
| No | 1066 (22.9) | 582 (25.4) | 482 (20.4) | 760 (21.8) | 306 (26.0) | ||
| On work, n (%) | ＜0.001 | 0.681 | |||||
| Yes | 835 (17.9) | 527 (23.0) | 308 (13.0) | 629 (18.1) | 206 (17.5) | ||
| No | 3822 (82.1) | 1764 (77.0) | 2054 (87.0) | 2853 (81.9) | 969 (82.5) | ||
| Use of glucose-lowering drugs within 30 days, n (%) | ＜0.001 | 0.35 | |||||
| Yes | 359 (7.8) | 109 (4.8) | 254 (10.8) | 262 (7.5) | 101 (8.6) | ||
| No | 4294 (92.2) | 2182 (95.2) | 2108 (89.2) | 3220 (92.5) | 1074 (91.4) | ||
| Use of insulin within 30 days, n (%) | ＜0.001 | 0.453 | |||||
| Yes | 100 (2.2) | 31 (1.4) | 73 (3.1) | 74 (2.1) | 30 (2.6) | ||
| No | 4553 (97.8) | 2260 (98.6) | 2289 (96.9) | 3408 (97.9) | 1145 (97.4) | ||
| Family history of stroke, n (%) | ＜0.001 | 0.858 | |||||
| Yes | 927 (19.9) | 496 (21.6) | 431 (18.2) | 691 (19.8) | 236 (20.1) | ||
| No | 3730 (80.1) | 1795 (78.4) | 1931 (81.8) | 2791 (80.2) | 939 (79.9) | ||
| Family history of coronary heart disease, n (%) | ＜0.001 | 0.074 | |||||
| Yes | 1127 (24.2) | 645 (28.2) | 481 (20.4) | 820 (23.5) | 307 (26.1) | ||
| No | 3530 (75.8) | 1464 (71.8) | 1881 (79.6) | 2662 (76.5) | 868 (73.9) | ||
Data were mean±SD or median (IQR) for skewed variables or numbers (proportions) for categorical variables.
RC remnant cholesterol, BMI body mass index, WHR waist-to-hip ratio, HbA1c glycosylated hemoglobin, FBG fasting blood glucose, PBG postprandial blood glucose, ALT alanine transferase, AST aspartate transferase, GGT gamma-glutamyl transferase, TG triglyceride, TC Total cholesterol, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, Non-HDL-C Non-high-density lipoprotein cholesterol, LCI lipoprotein combine index, eGFR estimated glomerular filtration rate, SBP systolic blood pressure, DBP diastolic blood pressure
Table 2 shows the odds ratio (OR) and 95% confidence intervals (CIs) of AS with the groups of the 10 lipid parameters. After further adjustments in Model 5, the third and fourth quartiles of RC (Q3: OR 1.35, 95% CI 1.11–1.64, P=0.003; Q4: OR 1.59, 95% CI 1.30–1.95, P＜0.001), fourth quartile of TC (Q4: OR 1.38, 95% CI 1.13–1.68, P=0.001 ),fourth quartiles of TG (Q4: OR 1.38, 95% CI 1.13–1.69, P＜0.001), fourth quartiles of non-HDL-C (Q4: OR 1.39, 95% CI 1.14–1.69, P=0.001), third and fourth quartiles of TG/HDL-C (Q3: OR 1.24, 95% CI 1.02–1.51, P=0.034; Q4: OR 1.49, 95% CI 1.21–1.82, P＜0.001), third and fourth quartiles of LDL-C/HDL-C (Q3: OR 1.28, 95% CI 1.06–1.56, P=0.012; Q4: OR 1.37, 95% CI 1.13–1.67, P=0.002), fourth quartiles of LCI (Q4: OR 1.50, 95% CI 1.22–1.83, P＜0.001), and the third and fourth quartiles of TC/HDL-C (Q3: OR 1.23, 95% CI 1.02–1.47, P=0.029; Q4: OR 1.37, 95%CI 1.14–1.65, P=0.001) remained significantly associated with AS. However, there was no correlation between LDL-C and HDL-C, and AS.
| Model Variable | Model 1 | Model 2 | Model 3 | Model 4 | Model 5 | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | |
| TC | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | 1 | |||||
| Q2 | 1.16 (0.97, 1.38) | 0.106 | 1.18 (0.99, 1.41) | 0.071 | 1.16 (0.97, 1.38) | 0.109 | 1.13 (0.93, 1.36) | 0.213 | 1.12 (0.93, 1.36) | 0.238 |
| Q3 | 1.28 (1.08, 1.53) | 0.005 | 1.27 (1.06, 1.52) | 0.008 | 1.25 (1.04, 1.49) | 0.016 | 1.16 (0.96, 1.41) | 0.126 | 1.14 (0.94, 1.38) | 0.189 |
| Q4 | 1.61 (1.35, 1.92) | ＜0.001 | 1.63 (1.36, 1.95) | ＜0.001 | 1.55 (1.29, 1.86) | ＜0.001 | 1.42 (1.17, 1.72) | ＜0.001 | 1.38 (1.13, 1.68) | 0.001 |
| TG | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | 1 | |||||
| Q2 | 1.16 (0.98, 1.39) | 0.087 | 1.14 (0.95, 1.36) | 0.161 | 1.13 (0.94, 1.35) | 0.194 | 1.06 (0.88, 1.28) | 0.55 | 1.05 (0.87, 1.28) | 0.6 |
| Q3 | 1.50 (1.26, 1.78) | ＜0.001 | 1.42 (1.19, 1.70) | ＜0.001 | 1.37 (1.14, 1.64) | 0.001 | 1.27 (1.04, 1.53) | 0.017 | 1.23 (1.01, 1.50) | 0.095 |
| Q4 | 1.99 (1.68, 2.38) | ＜0.001 | 1.83 (1.52, 2.20) | ＜0.001 | 1.73 (1.43, 2.08) | ＜0.001 | 1.46 (1.20, 1.78) | ＜0.001 | 1.38 (1.13, 1.69) | ＜0.001 |
| LDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | 1 | |||||
| Q2 | 1.05 (0.88, 1.25) | 0.612 | 1.04 (0.87, 1.24) | 0.671 | 1.04 (0.87, 1.24) | 0.677 | 1.04 (0.86, 1.26) | 0.683 | 1.04 (0.86, 1.25) | 0.718 |
| Q3 | 1.18 (0.99, 1.41) | 0.056 | 1.15 (0.96, 1.37) | 0.125 | 1.14 (0.96, 1.37) | 0.14 | 1.11 (0.92, 1.35) | 0.265 | 1.11 (0.91, 1.34) | 0.3 |
| Q4 | 1.39 (1.17, 1.66) | ＜0.001 | 1.36 (1.14, 1.63) | 0.001 | 1.33 (1.11, 1.59) | 0.002 | 1.25 (1.03, 1.51) | 0.026 | 1.21 (0.99, 1.47) | 0.055 |
| HDL-C | ||||||||||
| Q4 | 1 | 1 | 1 | 1 | 1 | |||||
| Q3 | 1.18 (0.99, 1.40) | 0.06 | 1.10 (0.92, 1.31) | 0.298 | 1.11 (0.93, 1.33) | 0.255 | 1.20 (0.99, 1.45) | 0.063 | 1.18 (0.98, 1.43) | 0.085 |
| Q2 | 1.25 (1.05, 1.49) | 0.011 | 1.12 (0.94, 1.34) | 0.205 | 1.13 (0.95, 1.36) | 0.173 | 1.18 (0.97, 1.43) | 0.094 | 1.16 (0.96, 1.41) | 0.126 |
| Q1 | 1.39 (1.17, 1.66) | ＜0.001 | 1.22 (1.01, 1.47) | 0.043 | 1.22 (1.0, 1.48) | 0.04 | 1.22 (0.99, 1.50) | 0.056 | 1.19 (0.97, 1.46) | 0.103 |
| Non-HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | 1 | |||||
| Q2 | 1.10 (0.92, 1.31) | 0.284 | 1.07 (0.90, 1.28) | 0.446 | 1.06 (0.89, 1.27) | 0.518 | 1.04 (0.86, 1.26) | 0.704 | 1.03 (0.85, 1.25) | 0.755 |
| Q3 | 1.37 (1.15, 1.63) | ＜0.001 | 1.28 (1.07, 1.53) | 0.007 | 1.25 (1.04, 1.49) | 0.016 | 1.16 (0.95, 1.40) | 0.14 | 1.13 (0.93, 1.37) | 0.213 |
| Q4 | 1.71 (1.43, 2.04) | ＜0.001 | 1.63 (1.36, 1.95) | ＜0.001 | 1.56 (1.30, 1.86) | ＜0.001 | 1.44 (1.19, 1.75) | ＜0.001 | 1.39 (1.14, 1.69) | 0.001 |
| RC | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | 1 | |||||
| Q2 | 1.24 (1.04, 1.47) | 0.018 | 1.17 (0.98, 1.40) | 0.083 | 1.16 (0.97, 1.39) | 0.099 | 1.19 (0.99, 1.45) | 0.069 | 1.18 (0.98, 1.44) | 0.085 |
| Q3 | 1.56 (1.31, 1.86) | ＜0.001 | 1.46 (122, 1.75) | ＜0.001 | 1.44 (1.20, 1.72) | ＜0.001 | 1.37 (1.13, 1.67) | 0.001 | 1.35 (1.11, 1.64) | 0.003 |
| Q4 | 2.16 (1.81, 2.57) | ＜0.001 | 1.98 (1.64, 2.38) | ＜0.001 | 1.89 (1.56, 2.28) | ＜0.001 | 1.67 (1.37, 2.04) | ＜0.001 | 1.59 (1.30, 1.95) | ＜0.001 |
| TG/HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | 1 | |||||
| Q2 | 1.27 (1.07, 1.52) | 0.007 | 1.20 (1.00, 1.43) | 0.048 | 1.19 (0.99, 1.42) | 0.062 | 1.19 (0.98, 1.44) | 0.075 | 1.19 (0.98, 1.44) | 0.086 |
| Q3 | 1.44 (1.21, 1.71) | ＜0.001 | 1.31 (1.10, 1.58) | 0.003 | 1.28 (1.07, 1.53) | 0.008 | 1.27 (1.05, 1.55) | 0.015 | 1.24 (1.02, 1.51) | 0.034 |
| Q4 | 2.03 (1.71, 2.42) | ＜0.001 | 1.82 (1.51, 2.20) | ＜0.001 | 1.74 (1.45, 2.10) | ＜0.001 | 1.57 (1.29, 1.92) | ＜0.001 | 1.49 (1.21, 1.82) | ＜0.001 |
| LDL-C/HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | 1 | |||||
| Q2 | 1.24 (1.04, 1.47) | 0.017 | 1.20 (1.01, 1.44) | 0.042 | 1.20 (1.00, 1.44) | 0.042 | 1.22 (1.01, 1.48) | 0.043 | 1.21 (0.99, 1.46) | 0.056 |
| Q3 | 1.45 (1.22, 1.72) | ＜0.001 | 1.34 (1.12, 1.60) | 0.002 | 1.33 (1.11, 1.60) | 0.002 | 1.31 (1.08, 1.58) | 0.007 | 1.28 (1.06, 1.56) | 0.012 |
| Q4 | 1.62 (1.36, 1.93) | ＜0.001 | 1.49 (1.24, 1.78) | ＜0.001 | 1.46 (1.22, 1.76) | ＜0.001 | 1.42 (1.17, 1.73) | ＜0.001 | 1.37 (1.13, 1.67) | 0.002 |
| LCI | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | 1 | |||||
| Q2 | 1.16 (0.97, 1.38) | 0.1 | 1.08 (0.91, 1.30) | 0.386 | 1.07 (0.89, 1.28) | 0.463 | 0.99 (0.82, 1.21) | 0.968 | 0.99 (0.82, 1.20) | 0.912 |
| Q3 | 1.45 (1.22, 1.72) | ＜0.001 | 1.32 (1.11, 1.59) | 0.002 | 1.29 (1.07, 1.54) | 0.006 | 1.21 (0.99, 1.46) | 0.059 | 1.18 (0.97, 1.43) | 0.095 |
| Q4 | 2.11 (1.77, 2.52) | ＜0.001 | 1.92 (1.60, 2.31) | ＜0.001 | 1.83 (1.52, 2.21) | ＜0.001 | 1.58 (1.30, 1.93) | ＜0.001 | 1.50 (1.22, 1.83) | ＜0.001 |
| TC/HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | 1 | |||||
| Q2 | 1.15 (0.96, 1.38) | 0.139 | 1.07 (0.89, 1.29) | 0.479 | 1.05 (0.87, 1.27) | 0.592 | 1.08 (0.88, 1.32) | 0.457 | 1.07 (0.88, 1.31) | 0.486 |
| Q3 | 1.39 (1.18, 1.64) | ＜0.001 | 1.29 (1.09, 1.53) | 0.003 | 1.28 (1.08, 1.51) | 0.005 | 1.25 (1.04, 1.50) | 0.017 | 1.23 (1.02, 1.47) | 0.029 |
| Q4 | 1.72 (1.46, 2.02) | ＜0.001 | 1.55 (1.30, 1.85) | ＜0.001 | 1.51 (1.27, 1.80) | ＜0.001 | 1.43 (1.19, 1.72) | ＜0.001 | 1.37 (1.14, 1.65) | 0.001 |
Model 1 was adjusted for age and sex; Model 2 was additionally adjusted for family history of coronary heart disease, family history of stroke, use of glucose-lowering drugs within 30 days, use of insulin within 30 days, exercise habits, occupation, smoking habit, drinking habit, BMI, WHR and neck circumference; Model 3 was additionally adjusted for ALT, AST, GGT and eGFR; Model 4 was additionally adjusted for SBP and DBP; Model 5 was additionally adjusted for FBG, PBG and HbA1c.
RC remnant cholesterol, BMI body mass index, WHR waist-to-hip ratio, HbA1c glycosylated hemoglobin, FBG fasting blood glucose, PBG postprandial blood glucose, ALT alanine transferase, AST aspartate transferase, GGT gamma-glutamyl transferase, TG triglyceride, TC Total cholesterol, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, Non-HDL-C Non-high-density lipoprotein cholesterol, LCI lipoprotein combine index, eGFR estimated glomerular filtration rate, SBP systolic blood pressure, DBP diastolic blood pressure
Tables 3 and 4 show the results of the stratified analyses by sex, BMI, blood glucose levels, and blood pressure, in that order.
| Varible | Gender a | P for interaction | BMI b | P for interaction | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Male | Female | BMI ＜24 Kg/m2 | BMI ≥ 24 Kg/m2 | |||||||
| OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | |||
| TC | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 0.95 (0.69, 1.30) | 0.726 | 0.99 (0.78, 1.26) | 0.936 | 0.908 | 1.27 (0.92, 1.75) | 0.149 | 1.03 (0.81, 1.31) | 0.798 | 0.957 |
| Q3 | 1.12 (0.82, 1.54) | 0.475 | 1.18 (0.93, 1.50) | 0.174 | 1.23 (0.89, 1.70) | 0.211 | 1.07 (0.841.36) | 0.607 | ||
| Q4 | 1.33 (0.96, 1.85) | 0.092 | 1.33 (1.04, 1.69) | 0.022 | 1.60 (1.15, 2.22) | 0.005 | 1.26 (0.99, 1.62) | 0.063 | ||
| TG | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.26 (0.91, 1.74) | 0.167 | 0.98 (0.77, 1.24) | 0.842 | 0.053 | 1.23 (0.89, 1.69) | 0.219 | 0.86 (0.68, 1.09) | 0.219 | 0.159 |
| Q3 | 1.32 (0.95, 1.83) | 0.095 | 1.19 (0.93, 1.52) | 0.164 | 1.51 (1.10, 2.09) | 0.012 | 1.15 (0.90, 1.46) | 0.267 | ||
| Q4 | 1.44 (1.02, 2.03) | 0.039 | 1.40 (1.09, 1.80) | 0.009 | 1.88 (1.34, 2.62) | ＜0.001 | 1.17 (0.91, 1.50) | 0.221 | ||
| LDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 0.92 (0.67, 1.26) | 0.593 | 0.97 (0.76, 1.23) | 0.809 | 0.453 | 0.99 (0.72, 1.35) | 0.923 | 1.03 (0.81, 1.31) | 0.813 | 0.365 |
| Q3 | 0.93 (0.67, 1.28) | 0.649 | 1.15 (0.90, 1.46) | 0.261 | 1.34 (0.98, 1.83) | 0.07 | 0.98 (0.77, 1.25) | 0.848 | ||
| Q4 | 1.27 (0.92, 1.77) | 0.148 | 1.20 (0.94, 1.52) | 0.146 | 1.39 (1.01, 1.92) | 0.045 | 1.10 (0.86, 1.41) | 0.461 | ||
| HDL-C | ||||||||||
| Q4 | 1 | 1 | 1 | 1 | ||||||
| Q3 | 1.25 (0.90, 1.73) | 0.177 | 1.02 (0.80, 1.31) | 0.878 | 0.977 | 0.89 (0.65, 1.26) | 0.481 | 0.95 (0.75, 1.21) | 0.7 | 0.402 |
| Q2 | 1.15 (0.82, 1.61) | 0.413 | 1.05 (0.83, 1.34) | 0.688 | 0.86 (0.62, 1.18) | 0.34 | 1.19 (0.94, 1.52) | 0.153 | ||
| Q1 | 1.51 (1.06, 2.14) | 0.021 | 1.01 (0.79, 1.28) | 0.948 | 0.78 (0.56, 1.08) | 0.134 | 0.96 (0.75, 1.24) | 0.778 | ||
| Non-HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.05 (0.77, 1.45) | 0.745 | 1.24 (0.97, 1.57) | 0.081 | 0.123 | 1.13 (0.82, 1.56) | 0.45 | 0.97 (0.77, 1.24) | 0.823 | 0.599 |
| Q3 | 0.96 (0.69, 1.33) | 0.794 | 1.22 (0.96, 1.55) | 0.113 | 1.36 (0.98, 1.88) | 0.069 | 1.03 (0.81, 1.31) | 0.819 | ||
| Q4 | 1.60 (1.14, 2.23) | 0.006 | 1.51 (1.18, 1.92) | 0.001 | 1.80 (1.30, 2.50) | ＜0.001 | 1.30 (1.02, 1.67) | 0.036 | ||
| RC | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.40 (1.01, 1.94) | 0.044 | 1.07 (0.85, 1.37) | 0.56 | 0.025 | 1.19 (0.86, 1.64) | 0.286 | 1.26 (0.99, 1.61) | 0.058 | 0.099 |
| Q3 | 1.29 (0.92, 1.79) | 0.136 | 1.42 (1.11, 1.81) | 0.005 | 1.44 (1.04, 2.00) | 0.029 | 1.20 (0.94, 1.52) | 0.143 | ||
| Q4 | 1.72 (1.21, 2.45) | 0.002 | 1.59 (1.23, 2.04) | ＜0.001 | 1.86 (1.33, 2.60) | ＜0.001 | 1.50 (1.17, 1.93) | 0.001 | ||
| TG/HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.05 (0.76, 1.45) | 0.773 | 1.10 (0.86, 1.40) | 0.452 | 0.182 | 1.27 (0.92, 1.75) | 0.147 | 0.92 (0.72, 1.17) | 0.472 | 0.042 |
| Q3 | 1.41 (1.00, 1.97) | 0.048 | 1.18 (0.93, 1.51) | 0.178 | 1.44 (1.04, 2.00) | 0.029 | 1.15 (0.90, 1.46) | 0.273 | ||
| Q4 | 1.41 (0.99, 2.00) | 0.053 | 1.42 (1.10, 1.83) | 0.007 | 1.73 (1.24, 2.42) | 0.001 | 1.12 (0.88, 1.44) | 0.36 | ||
| LDL-C/HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.17 (0.84, 1.61) | 0.35 | 1.10 (0.86, 1.40) | 0.448 | 0.226 | 1.10 (0.80, 1.52) | 0.56 | 0.93 (0.73, 1.18) | 0.555 | 0.395 |
| Q3 | 1.25 (0.90, 1.75) | 0.18 | 1.34 (1.05, 1.71) | 0.019 | 1.30 (0.94, 1.80) | 0.11 | 0.99 (0.78, 1.26) | 0.943 | ||
| Q4 | 1.60 (1.13, 2.25) | 0.007 | 1.24 (0.97, 1.58) | 0.09 | 1.63 (1.17, 2.26) | 0.004 | 1.08 (0.85, 1.38) | 0.536 | ||
| LCI | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 0.96 (0.69, 1.32) | 0.795 | 1.00 (0.79, 1.28) | 0.984 | 0.066 | 1.24 (0.90, 1.71) | 0.198 | 0.87 (0.68, 1.10) | 0.243 | 0.516 |
| Q3 | 1.15 (0.82, 1.60) | 0.414 | 1.20 (0.94, 1.54) | 0.14 | 1.20 (0.86, 1.66) | 0.28 | 1.08 (0.85, 1.37) | 0.556 | ||
| Q4 | 1.77 (1.24, 2.51) | 0.002 | 1.40 (1.09, 1.80) | 0.009 | 1.94 (1.39, 2.72) | ＜0.001 | 1.25 (0.98, 1.61) | 0.076 | ||
| TC/HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.05 (0.76, 1.45) | 0.763 | 1.19 (0.94, 1.52) | 0.152 | 0.258 | 1.01 (0.73, 1.40) | 0.941 | 0.99 (0.78, 1.27) | 0.977 | 0.472 |
| Q3 | 1.28 (0.92, 1.78) | 0.147 | 1.28 (1.00, 1.63) | 0.05 | 1.38 (0.99, 1.91) | 0.051 | 1.11 (0.87, 1.42) | 0.389 | ||
| Q4 | 1.63 (1.14, 2.31) | 0.007 | 1.38 (1.08, 1.77) | 0.011 | 1.73 (1.25, 2.41) | 0.001 | 1.14 (0.89, 1.46) | 0.298 | ||
a Adjusted for age, family history of coronary heart disease, family history of stroke, use of antihypertensive drugs within 30 days, use of glucose- lowering drugs within 30 days, use of insulin within 30 days, exercise habits, occupation, smoking habit, drinking habit, BMI, WHR, neck circumference, ALT, AST, GGT, eGFR, SBP, DBP, FBG, PBG and HbA1c.
b Adjusted for sex, age, family history of coronary heart disease, family history of stroke, use of glucose-lowering drugs within 30 days, use of insulin within 30 days, exercise habits, occupation, smoking habit, drinking habit, WHR, neck circumference, ALT, AST, GGT, eGFR, SBP, DBP, FBG, PBG and HbA1c.
RC remnant cholesterol, BMI body mass index, WHR waist-to-hip ratio, HbA1c glycosylated hemoglobin, FBG fasting blood glucose, PBG postprandial blood glucose, ALT alanine transferase, AST aspartate transferase, GGT gamma-glutamyl transferase, TG triglyceride, TC Total cholesterol, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, Non-HDL-C Non-high-density lipoprotein cholesterol, LCI lipoprotein combine index, eGFR estimated glomerular filtration rate, SBP systolic blood pressure, DBP diastolic blood pressure
| Varible | Blood Glucose a | P for interaction | Blood Pressure b | P for interaction | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Without diabetes | Diabetes | Hypertension | Without hypertension | |||||||
| OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | |||
| TC | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.09 (0.89, 1.34) | 0.408 | 0.99 (0.66, 1.52) | 0.997 | 0.806 | 1.11 (0.89, 1.38) | 0.346 | 1.13 (0.79, 1.62) | 0.49 | 0.878 |
| Q3 | 1.11 (0.90, 1.37) | 0.33 | 1.15 (0.75, 1.77) | 0.513 | 1.22 (0.97, 1.52) | 0.086 | 1.03 (0.72, 1.49) | 0.859 | ||
| Q4 | 1.40 (1.13, 1.74) | 0.002 | 1.24 (0.80, 1.92) | 0.329 | 1.40 (1.12, 1.76) | 0.004 | 1.43 (0.99, 2.07) | 0.06 | ||
| TG | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.09 (0.89, 1.34) | 0.421 | 0.85 (0.54, 1.35) | 0.494 | 0.577 | 1.02 (0.81, 1.28) | 0.874 | 1.22 (0.86, 1.73) | 0.258 | 0.756 |
| Q3 | 1.25 (1.01, 1.54) | 0.038 | 1.21 (0.76, 1.91) | 0.422 | 1.27 (1.01, 1.59) | 0.041 | 1.30 (0.91, 1.87) | 0.151 | ||
| Q4 | 1.41 (1.13, 1.75) | 0.002 | 1.38 (0.88, 2.17) | 0.157 | 1.40 (1.1, 1.77) | 0.004 | 1.70 (1.16, 2.51) | 0.007 | ||
| LDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 0.99 (0.81, 1.22) | 0.95 | 1.07 (0.71, 1.63) | 0.745 | 0.754 | 0.99 (0.80, 1.24) | 0.958 | 1.04 (0.73, 1.50) | 0.814 | 0.815 |
| Q3 | 1.04 (0.85, 1.28) | 0.708 | 1.13 (0.74, 1.73) | 0.581 | 1.03 (0.83, 1.28) | 0.793 | 1.27 (0.89, 1.81) | 0.197 | ||
| Q4 | 1.22 (0.99, 1.51) | 0.065 | 1.14 (0.74, 1.75) | 0.551 | 1.19 (0.95, 1.49) | 0.133 | 1.31 (0.91, 1.89) | 0.154 | ||
| HDL-C | ||||||||||
| Q4 | 1 | 1 | 1 | 1 | ||||||
| Q3 | 1.21 (0.99, 1.49) | 0.068 | 1.22 (0.77, 1.94) | 0.391 | 0.553 | 1.24 (0.99, 1.56) | 0.06 | 0.96 (0.67, 1.35) | 0.796 | 0.254 |
| Q2 | 1.14 (0.93, 1.41) | 0.211 | 1.13 (0.72, 1.76) | 0.607 | 1.14 (0.91, 1.43) | 0.256 | 1.25 (0.87, 1.79) | 0.225 | ||
| Q1 | 1.15 (0.92, 1.44) | 0.228 | 1.45 (0.91, 2.32) | 0.118 | 1.10 (0.87, 1.39) | 0.414 | 1.42 (0.96, 2.12) | 0.082 | ||
| Non-HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 0.97 (0.79, 1.20) | 0.792 | 1.02 (0.67, 1.58) | 0.913 | 0.63 | 1.04 (0.83, 1.30) | 0.727 | 0.97 (0.68, 1.40) | 0.881 | 0.985 |
| Q3 | 1.10 (0.89, 1.36) | 0.388 | 1.12 (0.72, 1.73) | 0.622 | 1.18 (0.94, 1.47) | 0.156 | 1.20 (0.84, 1.74) | 0.321 | ||
| Q4 | 1.38 (1.11, 1.70) | 0.003 | 1.39 (0.89, 2.16) | 0.148 | 1.41 (1.12, 1.77) | 0.003 | 1.57 (1.09, 2.26) | 0.016 | ||
| RC | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.17 (0.95, 1.43) | 0.144 | 1.49 (0.94, 2.38) | 0.092 | 0.395 | 1.12 (0.89, 1.40) | 0.33 | 1.33 (0.93, 1.89) | 0.113 | 0.717 |
| Q3 | 1.34 (1.09, 1.66) | 0.006 | 1.46 (0.92, 2.31) | 0.105 | 1.25 (1.10, 1.58) | 0.052 | 1.92 (1.34, 2.75) | ＜0.001 | ||
| Q4 | 1.54 (1.23, 1.92) | ＜0.001 | 2.15 (1.35, 3.42) | 0.001 | 1.58 (1.25, 1.99) | ＜0.001 | 1.86 (1.25, 2.78) | 0.002 | ||
| TG/HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.19 (0.97, 1.46) | 0.099 | 1.18 (0.74, 1.91) | 0.486 | 0.745 | 1.10 (0.88, 1.39) | 0.395 | 1.47 (1.03, 2.09) | 0.032 | 0.756 |
| Q3 | 1.26 (1.02, 1.56) | 0.032 | 1.22 (0.76, 1.96) | 0.418 | 1.14 (0.91, 1.44) | 0.25 | 1.57 (1.08, 2.26) | 0.017 | ||
| Q4 | 1.45 (1.17, 1.81) | 0.001 | 1.82 (1.13, 2.94) | 0.014 | 1.39 (1.10, 1.75) | 0.006 | 2.08 (1.40, 3.10) | ＜0.001 | ||
| LDL-C/HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.15 (0.94, 1.42) | 0.186 | 1.41 (0.90, 2.21) | 0.135 | 0.646 | 1.43 (1.14, 1.80) | 0.002 | 0.87 (0.61, 1.25) | 0.452 | 0.029 |
| Q3 | 1.24 (1.00, 1.53) | 0.046 | 1.40 (0.91, 2.17) | 0.126 | 1.34 (1.07, 1.68) | 0.01 | 1.18 (0.82, 1.70) | 0.382 | ||
| Q4 | 1.29 (1.04, 1.60) | 0.021 | 1.59 (1.02, 2.48) | 0.04 | 1.34 (1.07, 1.68) | 0.012 | 1.66 (1.15, 2.39) | 0.007 | ||
| LCI | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.02 (0.83, 1.25) | 0.874 | 0.94 (0.59, 1.49) | 0.782 | 0.382 | 0.98 (0.78, 1.95) | 0.828 | 1.04 (0.73, 1.49) | 0.827 | 0.972 |
| Q3 | 1.16 (0.94, 1.43) | 0.178 | 1.27 (0.81, 2.00) | 0.304 | 1.14 (0.90, 1.43) | 0.279 | 1.44 (1.01, 2.06) | 0.043 | ||
| Q4 | 1.53 (1.23, 1.91) | ＜0.001 | 1.47 (0.93, 2.30) | 0.096 | 1.55 (1.22, 1.95) | ＜0.001 | 1.65 (1.13, 2.41) | 0.01 | ||
| TC/HDL-C | ||||||||||
| Q1 | 1 | 1 | 1 | 1 | ||||||
| Q2 | 1.10 (0.88, 1.36) | 0.398 | 0.99 (0.62, 1.59) | 0.965 | 0.634 | 1.08 (0.85, 1.36) | 0.533 | 1.01 (0.69, 1.46) | 0.975 | 0.878 |
| Q3 | 1.18 (0.97, 1.44) | 0.103 | 1.29 (0.86, 1.95) | 0.221 | 1.15 (0.93, 1.42) | 0.189 | 1.46 (1.04, 2.06) | 0.031 | ||
| Q4 | 1.35 (1.10, 1.66) | 0.004 | 1.49 (0.98, 2.27) | 0.064 | 1.34 (1.08, 1.66) | 0.088 | 1.55 (1.09, 2.21) | 0.016 | ||
a Adjusted for age, sex, family history of coronary heart disease, family history of stroke, use of glucose-lowering drugs within 30 days, use of insulin within 30 days, exercise habits, occupation, smoking habit, drinking habit, BMI, WHR, neck circumference, ALT, AST, GGT, eGFR, SBP and DBP.
b Adjusted for age, sex, family history of coronary heart disease, family history of stroke, use of glucose-lowering drugs within 30 days, use of insulin within 30 days, exercise habits, occupation, smoking habit, drinking habit, BMI, WHR, neck circumference, ALT, AST, GGT, eGFR, FBG, PBG and HbA1c.
RC remnant cholesterol, BMI body mass index, WHR waist-to-hip ratio, HbA1c glycosylated hemoglobin, FBG fasting blood glucose, PBG postprandial blood glucose, ALT alanine transferase, AST aspartate transferase, GGT gamma-glutamyl transferase, TG triglyceride, TC Total cholesterol, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, Non-HDL-C Non-high-density lipoprotein cholesterol, LCI lipoprotein combine index, eGFR estimated glomerular filtration rate, SBP systolic blood pressure, DBP diastolic blood pressure
In men, TG (Q4: OR 1.44, 95% CI 1.02–2.03, P=0.039), HDL-C (Q1: OR 1.51, 95% CI 1.06–2.14, P=0.021), non-HDL-C (Q4: OR 1.60, 95% CI 1.14–2.23, P=0.006), RC (Q4: OR 1.72, 95% CI 1.21–2.45, P=0.002), LDL-C/HDL-C (Q4: OR 1.60, 95% CI 1.13–2.25, P=0.007), LCI (Q4: OR 1.77, 95% CI 1.24–2.51, P=0.002), and TC/HDL-C (Q4: OR 1.63, 95% CI 1.14–2.31, P=0.007) were all significantly associated with AS, whereas TC (Q4: P=0.092), LDL-C (Q4: P=0.148), and TG/ HDL-C (Q4: P=0.53) were not.
In women, TC (Q4: OR 1.33, 95% CI 1.04–1.69, P=0.022), TG (Q4: OR 1.40, 95% CI 1.09–1.80, P=0.009), non-HDL- C(Q4: OR 1.51, 95% CI 1.18–1.92, P=0.001), RC (Q4: OR 1.59, 95% CI 1.23–2.04, P＜0.001), TG/HDL-C (Q4: OR 1.42, 95% CI 1.10–1.83, P=0.007), LCI (Q4: OR 1.40, 95% CI 1.09–1.80, P=0.009), and TC/HDL-C (Q4: OR 1.38, 95% CI 1.08–1.77, P=0.011) were significantly associated with AS, whereas HDL-C (Q4: P=0.948), LDL-C (Q4: P=0.146), and LDL-C/HDL-C (Q4: P=0.09) were not.
It was also found that there was an interaction only between RC (P for interaction =0.025) and sex and none for the rest of the lipid parameters.
In participants with a BMI of ＜24 kg/m2, the following parameters were significantly associated with AS: TC (Q4: OR 1.60, 95% CI 1.15–2.22, P=0.005), TG (Q4: OR 1.88, 95% CI 1.34–2.62, P＜0.001), LDL-C (Q4: OR 1.39, 95% CI 1.01–1.92, P=0.045), non-HDL-C (Q4: OR 1.80, 95% CI 1.30–2.50, P＜0.001), RC (Q4: OR 1.86, 95% CI 1.33–2.60, P＜0.001), TG/HDL-C (Q4: OR 1.73, 95% CI 1.24–2.42, P=0.001), LDL-C/HDL-C (Q4: OR 1.63, 95% CI 1.17–2.26, P=0.004), LCI (Q4: OR 1.94, 95% CI 1.39–2.72, P＜0.001), and TC/HDL-C (Q4: OR 1.73, 95% CI 1.25–2.41, P=0.001); whereas, HDL-C (Q4: P=0.134) was not.
In participants with a BMI of ≥ 24 kg/m2, only non-HDL-C (Q4: OR 1.30, 95% CI 1.02–1.67, P=0.036) and RC (Q4: OR 1.50, 95% CI 1.17–1.93, P=0.001) were significantly associated with AS, whereas TC (Q4: P=0.063), TG (Q4: P=0.221), LDL-C (Q4: P=0.461), HDL-C (Q4: P=0.778), TG/HDL-C (Q4: P=0.36), LDL-C/HDL-C (Q4: P=0.536), LCI (Q4: P=0.076), and TC/HDL-C (Q4: P=0.298) were not.
An interaction between TG/HDL-C and BMI was found (P for interaction =0.042). There was none in the remaining lipid parameters.
In participants without diabetes, TC (Q4: OR 1.40, 95% CI 1.13–1.74, P=0.002), TG (Q4: OR 1.41, 95% CI 1.13–1.75, P=0.002), non-HDL-C (Q4: OR 1.38, 95% CI 1.11–1.70, P=0.003), RC (Q4: OR 1.54, 95% CI 1.23–1.92, P＜0.001), TG/HDL-C (Q4: OR 1.45, 95% CI 1.17–1.81, P=0.001), LDL-C/HDL-C (Q4: OR 1.29, 95% CI 1.04–1.60, P=0.021), LCI (Q4: OR 1.53, 95% CI 1.23–1.91, P＜0.001), and TC/HDL-C (Q4: OR 1.35, 95% CI 1.10–1.66, P=0.004) were significantly associated with AS; whereas, LDL-C (Q4: P=0.065) and HDL-C (Q4: P=0.228) were not.
In participants with diabetes, only RC (Q4: OR 2.15, 95% CI 1.35–3.42, P=0.001), TG/HDL-C (Q4: OR 1.82, 95% CI 1.13–2.94, P=0.014), and LDL-C/HDL-C (Q4: OR 1.59, 95% CI 1.02–2.48, P=0.04) were significantly associated with AS; whereas, TC (Q4: P=0.329), TG (Q4: P=0.157), LDL-C (Q4: P=0.551), HDL-C (Q4: P=0.118), non-HDL-C (Q4: P=0.148), LCI (Q4: P=0.096), and TC/HDL-C (Q4: P=0.064) were not.
There was no interaction between any of these 10 lipid parameters and blood glucose levels.
In participants without hypertension, the following parameters were significantly associated with AS: TG (Q4: OR 1.70, 95% CI 1.16–2.51, P=0.007), non-HDL-C (Q4: OR 1.57, 95% CI 1.09–2.26, P=0.016), RC (Q4: OR 1.86, 95% CI 1.25–2.78, P=0.002), TG/HDL-C (Q4: OR 2.08, 95% CI 1.40–3.10, P＜0.001), LDL-C/HDL-C (Q4: OR 1.66, 95% CI 1.15–2.39, P=0.007), LCI (Q4: OR 1.65, 95% CI 1.13–2.41, P=0.01), and TC/HDL-C (Q4: OR 1.55, 95% CI 1.09–2.21, P=0.016); whereas, TC (Q4: P=0.06), LDL-C (Q4: P=0.154), and HDL-C (Q4: P=0.082) were not.
In participants with hypertension, the following parameters were associated with AS: TC (Q4: OR 1.40, 95% CI 1.12–1.76, P=0.004), TG (Q4: OR 1.70, 95% CI 1.16–2.51, P=0.007), non-HDL-C (Q4: OR 1.41, 95% CI 1.12–1.77, P=0.003), RC (Q4: OR 1.58, 95% CI 1.25–1.99, P＜0.001), TG/HDL-C (Q4: OR 1.39, 95% CI 1.10–1.75, P=0.006), LDL-C/HDL-C (Q4: OR 1.34, 9% CI 1.07–1.68, P=0.012), and LCI (Q4: OR 1.55, 95% CI 1.22–1.95, P＜0.001); whereas, LDL-C (Q4: P=0.133), HDL-C (Q4: P=0.414), and TC/HDL-C (Q4: P=0.088) were not.
Only the interaction between LDL-C/HDL-C and blood pressure was present (P for interaction =0.029), whereas there was none for the remaining lipid parameters.
In Table 5, RC and AS were still significantly associated when TG ＜1.70 mmol/L (Q3: OR 1.29, 95% CI 1.03–1.60, P=0.024; Q4: OR 1.58, 95% CI 1.02–2.45, P=0.04), LDL-C ＜3.4 mmol/L (Q4: OR 1.32, 95% CI 1.01–1.73, P=0.041), HDL-C ≥ 1.0 mmol/L (Q3: OR 1.36, 95% CI 1.12–1.67, P=0.002; Q4: OR 1.67, 95% CI 1.34–2.08, P＜0.001), or non-HDL-C ＜4.1 mmol/L (Q4: OR 1.42, 95% CI 1.10–1.82, P=0.007).
| Lipid levels RC | TG＜1.7 mmol/L | LDL-C＜3.4 mmol/L | HDL-C ≥ 1 mmol/L | Non-HDL-C＜4.1 mmol/L | ||||
|---|---|---|---|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | |
| Q1 | 1 | 1 | 1 | 1 | ||||
| Q2 | 1.14 (0.94, 1.39) | 0.192 | 1.06 (0.84, 1.35) | 0.606 | 1.20 (0.98, 1.45) | 0.073 | 1.13 (0.92, 1.39) | 0.249 |
| Q3 | 1.29 (1.03, 1.60) | 0.024 | 1.09 (0.85, 1.41) | 0.507 | 1.36 (1.12, 1.67) | 0.002 | 1.23 (0.99, 1.54) | 0.065 |
| Q4 | 1.58 (1.02, 2.45) | 0.04 | 1.32 (1.01, 1.73) | 0.041 | 1.67 (1.34, 2.08) | ＜0.001 | 1.42 (1.10, 1.82) | 0.007 |
Adjusted for age, sex, family history of coronary heart disease, family history of stroke, use of glucose-lowering drugs within 30 days, use of insulin within 30 days, exercise habits, occupation, smoking habit, drinking habit, BMI, WHR, neck circumference, ALT, AST, GGT, eGFR, SBP, DBP, FBG, PBG and HbA1c.
RC remnant cholesterol, BMI body mass index, WHR waist-to-hip ratio, HbA1c glycosylated hemoglobin, FBG fasting blood glucose, PBG postprandial blood glucose, ALT alanine transferase, AST aspartate transferase, GGT gamma-glutamyl transferase, TG triglyceride, TC Total cholesterol, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, Non-HDL-C Non-high-density lipoprotein cholesterol, LCI lipoprotein combine index, eGFR estimated glomerular filtration rate, SBP systolic blood pressure, DBP diastolic blood pressure
In the sensitivity analyses, we found that RC and the ≥ 75th percentile baPWV remained significantly correlated in Model 5, and the OR of RC (Q3: OR 1.32, 95% CI 1.04–1.67, P=0.02; Q4: OR 1.76, 95% CI 1.39–2.22, P＜0.001) was significantly higher than that of other lipid parameters (Supplementary Table 1). In addition, even after correcting for confounders in Model 5 and TG, LDL-C, HDL-C, and TC, RC and AS remained significantly correlated (Q3: OR 1.30, 95% CI 1.05–1.62, P=0.017; Q4: OR 1.43, 95% CI 1.09–1.88, P=0.01) (Supplementary Table 2).
| Model Variable | Model 5 | |
|---|---|---|
| OR (95% CI) | P value | |
| TC | ||
| Q1 | 1 | |
| Q2 | 1.03 (0.82, 1.28) | 0.829 |
| Q3 | 1.21 (0.97, 1.52) | 0.091 |
| Q4 | 1.22 (0.97, 1.53) | 0.09 |
| TG | ||
| Q1 | 1 | |
| Q2 | 1.13 (0.89, 1.43) | 0.312 |
| Q3 | 1.35 (1.07, 1.70) | 0.011 |
| Q4 | 1.67 (1.32, 2.11) | ＜0.001 |
| LDL-C | ||
| Q1 | 1 | |
| Q2 | 1.05 (0.85, 1.32) | 0.64 |
| Q3 | 1.05 (0.84, 1.32) | 0.649 |
| Q4 | 1.12 (0.88, 1.40) | 0.314 |
| HDL-C | ||
| Q4 | 1 | |
| Q3 | 1.05 (0.84, 1.32) | 0.681 |
| Q2 | 1.13 (0.90, 1.42) | 0.293 |
| Q1 | 1.21 (0.96, 1.53) | 0.111 |
| Non-HDL-C | ||
| Q1 | 1 | |
| Q2 | 0.97 (0.77, 1.22) | 0.783 |
| Q3 | 1.07 (0.86, 1.34) | 0.538 |
| Q4 | 1.34 (1.07, 1.68) | 0.011 |
| RC | ||
| Q1 | 1 | |
| Q2 | 1.24 (0.98, 1.57) | 0.071 |
| Q3 | 1.32 (1.04, 1.67) | 0.02 |
| Q4 | 1.76 (1.39, 2.22) | ＜0.001 |
| TG/HDL-C | ||
| Q1 | 1 | |
| Q2 | 1.30 (1.03, 1.64) | 0.029 |
| Q3 | 1.40 (1.10, 1.77) | 0.006 |
| Q4 | 1.60 (1.26, 2.02) | ＜0.001 |
| LDL-C/HDL-C | ||
| Q1 | 1 | |
| Q2 | 1.20 (0.96, 1.50) | 0.117 |
| Q3 | 1.08 (0.86, 1.36) | 0.484 |
| Q4 | 1.20 (0.96, 1.51) | 0.112 |
| LCI | ||
| Q1 | 1 | |
| Q2 | 1.12 (0.89, 1.41) | 0.33 |
| Q3 | 1.14 (0.90, 1.43) | 0.286 |
| Q4 | 1.53 (1.21, 1.93) | ＜0.001 |
| TC/HDL-C | ||
| Q1 | 1 | |
| Q2 | 1.01 (0.80, 1.28) | 0.942 |
| Q3 | 1.02 (0.82, 1.26) | 0.876 |
| Q4 | 1.31 (1.06, 1.63) | 0.013 |
Adjusted for age, sex, family history of coronary heart disease, family history of stroke, use of glucose-lowering drugs within 30 days, use of insulin within 30 days, exercise habits, occupation, smoking habit, drinking habit, BMI, WHR, neck circumference, ALT, AST, GGT, eGFR, SBP, DBP, FBG, PBG and HbA1c.
RC remnant cholesterol, BMI body mass index, WHR waist-to-hip ratio, HbA1c glycosylated hemoglobin, FBG fasting blood glucose, PBG postprandial blood glucose, ALT alanine transferase, AST aspartate transferase, GGT gamma-glutamyl transferase, TG triglyceride, TC Total cholesterol, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, Non-HDL-C Non-high-density lipoprotein cholesterol, LCI lipoprotein combine index, eGFR estimated glomerular filtration rate, SBP systolic blood pressure, DBP diastolic blood pressure
| Model Variable | Model 5+TG, LDL-C, HDL-C and TC | |
|---|---|---|
| OR (95% CI) | P value | |
| RC | ||
| Q1 | 1 | |
| Q2 | 1.17 (0.96, 1.43) | 0.117 |
| Q3 | 1.30 (1.05, 1.62) | 0.017 |
| Q4 | 1.43 (1.09, 1.88) | 0.01 |
Adjusted for age, sex, family history of coronary heart disease, family history of stroke, use of glucose-lowering drugs within 30 days, use of insulin within 30 days, exercise habits, occupation, smoking habit, drinking habit, BMI, WHR, neck circumference, ALT, AST, GGT, eGFR, SBP, DBP, FBG, PBG , HbA1c, TG, TC, HDL-C and LDL-C.
RC remnant cholesterol, BMI body mass index, WHR waist-to-hip ratio, HbA1c glycosylated hemoglobin, FBG fasting blood glucose, PBG postprandial blood glucose, ALT alanine transferase, AST aspartate transferase, GGT gamma-glutamyl transferase, TG triglyceride, TC Total cholesterol, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, eGFR estimated glomerular filtration rate, SBP systolic blood pressure, DBP diastolic blood pressure
To the best of our knowledge, this is the first study on the relationship between RC and AS in a large sample of Chinese community residents. Our study has the following findings: (1) the combined lipid parameters are generally more associated with AS than the individual lipid parameters; (2) RC was more strongly associated with AS than TG, TC, HDL-C, LDL-C, non-HDL-C, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, or LCI; (3) further stratified analysis showed that RC was significantly associated with AS in both sexes and at any blood glucose, blood pressure, and BMI levels; however, the remaining nine lipid parameters could only be correlated with AS under some specific stratification; (4) RC was still associated with AS even when TG, LDL-C, HDL-C, or non-HDL-C was at the appropriate level recommended by the guidelines.
Our results show that combined lipid parameters, especially RC, correlate better with AS than traditional individual lipid parameters. Previous studies on the relationship between traditional lipid parameters and AS have shown inconsistent results9, 28-31). We hypothesized that the differences between study results could be explained by differences in the sample size, the status of the study population (health or disease status), how AS was quantified, and various adjustment variables. Large sample studies tend to show that TG and AS are correlated, whereas LDL-C and TC are not correlated or weakly correlated with AS. Our study also found that LDL-C was not correlated with AS after adjustment for potential confounders, which was consistent with the results of previous large sample studies. In addition, we found that non-traditional lipid parameters such as RC, non-HDL-C, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, and LCI generally performed better than traditional lipids in terms of association with AS. Using a composite index generated from multiple traditional lipids could suggest an imbalance between atherogenic and protective lipoproteins and also surmount discordance in the evaluation of different lipid parameters. However, most studies in recent years have focused on lipid ratios6, 9, 19-22, 26), while the association between RC and AS is very limited.
A recent study of 912 participants of the general Japanese population found that RC was significantly associated with AS, represented by elevated baPWV, and RC was more strongly associated with AS than non-HDL-C, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, and LCI11). However, their study only compared RC and combined lipid parameters, whereas the present study compared RC and combined and traditional lipid parameters for the association with AS. In addition, their study did not adjust for confounders when comparing the association between RC, combined lipid parameters, and AS, whereas our study adequately adjusted for potential confounders. Therefore, the findings of the current study are more convincing. Moreover, the participants in the current study were a large sample of the general Chinese population, further suggesting that RC is the lipid parameter with the strongest correlation with AS in different Asian ethnic groups.
The mechanism of the strong association between RC and AS has not been fully elucidated, and we speculate the following reasons: RC could enter the subendothelial space through scavenger receptors, promote the formation of foam cells, and increase the toxicity of smooth muscle32), leading to the formation of atherosclerotic plaques, which in turn leads to AS33). Besides, RC would cause slow-motion inflammation of the vessel wall13), which stimulates leukocytes to release large amounts of cytokines and adhesion molecules, resulting in leukocyte adhesion to the vascular endothelium and invasion of the intima, leading to an increase in vascular damage and resistance34). In addition, several studies35, 36) have reported that RC and insulin resistance are highly correlated. Insulin resistance with hyperlipidemia is characterized by increased intracellular calcium concentrations, increased collagen and advanced glycosylation end products, fibrosis and cellular proliferation, reduced arterial elasticity through arterial remodeling, and AS37).
The major components of RC, very-low-density lipoprotein cholesterol (VLDL-C) and intermediate-density lipoprotein cholesterol (IDL-C), are strongly associated with the number and pro-inflammatory status of macrophages in visceral adipose tissue38), which contribute to the maintenance of the local inflammatory response by secreting pro-inflammatory cytokines, chemokines, and producing reactive oxygen and nitrogen species. This persistent inflammation drives the apoptosis of macrophages, which, in the absence of effective cytostatic action, leads to the accumulation of debris and apoptotic cells that promote the formation of necrotic cores in atherosclerotic plaques39).
Previous authors suggested that the relationship between lipid parameters and AS might be sex-specific40). A study of a Caucasian population showed a stronger association between baPWV values and metabolic syndrome components in males than in females10). Similar to previous studies, the current study also found that the ORs of these lipid parameters were higher in males than in females. Gender is a proverbial derogatory factor and has a derogatory effect on men41), which might explain the gender differences in these studies on AS. We found that among traditional lipids, only TG was associated with AS in both sexes, and this association was lower than the combined lipid parameters (especially in males), which further suggested the limitations of traditional lipids in predicting AS.
In further stratified analysis, we found that only RC, TG/HDL-C, and LDL-C/HDL-C were significantly associated with AS in both participants with and without diabetes; only TG, RC, non-HDL-C, TG/HDL-C, LDL-C/HDL-C, and LCI were associated with AS in participants with and without hypertension; only RC and non-HDL-C were associated with AS in overweight or non-overweight participants. It could be seen that there is no correlation between conventional individual lipids and AS in people with metabolic abnormalities such as diabetes, hypertension, or those who are overweight, except in the population with hypertension, where only TG and TC are correlated with AS, which further suggests the limitation of traditional lipids in predicting AS. We hypothesized that being overweight and having hyperglycemia and hypertension would have a greater effect on AS than traditional lipid parameters. Notably, only one lipid parameter, RC, was significantly associated with AS in any sex, blood glucose levels, blood pressure levels, and BMI stratification, suggesting that the association between RC and AS is stable, and the adverse effects of RC on AS are not easily masked by other metabolic syndrome risk factors. We consider this to be very clinically significant. RC is closely associated with AS in both healthy individuals and those with metabolic risk factors. RC, as an indicator of whether one has AS, is adapted to a wide range of people and is not affected by other risk factors for metabolic syndrome.
The current study is the first to report that RC and AS remain significantly associated when LDL-C, HDL-C, TG, or non-HDL-C is at ideal levels recommended by the guidelines. Many people, even with the ideal LDL-C levels, undergo CVD events or atherosclerotic progress42), which is referred to as “residual risk,”43) and it could not even be determined by measuring LDL-C3). RC might explain this “residual risk.” Although LDL-C is important in the formation of atherosclerosis, it accounts for only about 75% of atherosclerotic lipoproteins44, 45), and an additional 25% of VLDL -C (an important component of RC) also contributes to this process44, 45). In addition, compared with LDL-C, RC is smaller and could be directly phagocytosed by macrophages to form foam cells, and LDL-C only leads to atherosclerosis after oxidation, so RC is more antiatherogenic15). Moreover, Varbo et al. carried out a Mendelian randomization study demonstrating that LDL-C could not result in inflammation and that the inflammatory components of atherosclerosis are induced by elevated RC13). As mentioned above, RC-induced inflammation is also one of the important causes of AS.
Some research aimed at increasing HDL-C levels to reduce the risk of CVD were unsuccessful, and this controversy still continues46). Further, one Mendelian randomized study disproved HDL-C as a protective factor for CVD47). The current study also shows that high HDL-C levels could not reduce the risk of AS due to high RC. In fact, there might be no causality between AS or atherosclerosis and low levels of HDL-C; low HDL-C is simply a marker of high RC48). Besides, RC facilitates the reformulation of HDL-C into smaller, low-cholesterol particles that might be deficient in atherosclerotic protection independent of HDL-C levels49).
A 2020 Icelandic research suggested that the deleterious effects of the genetic variations in the elevation of TG were actually mediated by the atherogenic effects of RC50). As plenty of cells are capable of degrading TG, it is unlikely that TG itself leads to AS, but since no cells could degrade cholesterol, RC is considered the major contributor to AS13). In addition, high RC has been reported to contribute to the risk of atherosclerosis even in populations with normal TG levels51). The current study demonstrates that even at normal TG levels, high RC could cause AS, which is an early manifestation of atherosclerosis.
Though it has been shown that non-HDL-C could be presented as an alternative to RC52), and prior literature has revealed that non-HDL-C could be served as an independent predictive factor of CVD18), the current study in a large Chinese population and the study by Wang et al. in a Japanese population11) demonstrated that the association between non-HDL-C and AS is not as strong as the association between RC and AS. Furthermore, the current study found that the correlation between RC and AS remained significant and stable despite guideline-recommended ideal levels of non-HDL-C. Therefore, we do not support that non-HDL-C is a suitable alternative to RC, and we suggest that even if routine lipid testing meets the guideline recommendations, the risk of AS implied by high RC cannot be ignored. We hope that in the future, RC, similar to non-HDL-C, would have uniform abnormal values specified in the guidelines, allowing the early detection of RC abnormalities and prevent related diseases.
The current study is the first to compare the association between RC, traditional lipid parameters, and lipid ratios and AS in a large sample of the Chinese general population. We also adequately adjusted for potential confounders. This study also innovatively investigated the association between RC and AS when traditional lipid parameters were at the ideal levels recommended by the guidelines. However, some limitations are inevitable. First, this is a single-center study; second, this is a cross-sectional study, so we could only draw associations, not causations. We hope that future multicenter cohort studies would further validate the conclusions of the current study. Third, oxidized LDL, small dense LDL, and the major components of RC (VLDL-C, IDL-C, and celiac particles), were not tested in this study. However, RC can be calculated using test data from routine physical examinations, which is cheap and convenient. Fourth, the study population in this study was a high-risk group for AS, that is, middle-aged and older adults over 40 years of age, so we are not sure whether the findings of this study could be generalized to the entire age group.
In brief, we found that RC was more closely associated with AS than traditional lipid parameters and lipid ratios in the general Chinese population and was significantly correlated with AS regardless of sex, age, blood glucose, blood pressure, and BMI levels. We also found that RC was strongly associated with AS even when LDL-C, HDL-C, TG, or non-HDL-C was at the ideal levels recommended by the guidelines. This study adds to the novel evidence that RC is strongly associated with a high risk of residual CVD, probably due to its adverse influence on AS. RC could be calculated from conventional lipid tests, which is simple and inexpensive. The significant association between RC and AS also suggests that the current lipid assessments needs to be further improved. Adding RC to the assessment of AS in clinical practice has broad application prospects.
The datasets are not freely available due to participants’ privacy protection.
The study is supported by Beijing Municipal Science and Technology Commission Project (Z201100005520014), PLA General Hospital Youth Independent Innovation Science Fund project (22QNFC052).
We would like to thank the participants in this study.
The authors declare no competing interests.
Not applicable.
All participants provided informed consent. The protocol of this study was approved by the Committee on Human Research of the Chinese People’s Liberation Army General Hospital.
BL contributed to the conception and design of the study. BL, XZ, YL and YZ recruited the subjects and supervised the study. BL analyzed the data and wrote the initial draft of the paper. YM and BL contributed to the writing, reviewing, and revising of the manuscript. All authors contributed to the article and approved the submitted version.
