Article Figures & Data
Figures
- Figure 1.
Cohort construction. (A) Flow diagram of cohort assembly. (B) Timeline of cohort selection.
- Figure 2.
Risk of all-cause mortality by HDL cholesterol (HDL-C) levels in each eGFR category. Error bars represent 95% confidence intervals.
- Figure 3.
Spline analyses of all-cause mortality by HDL cholesterol (HDL-C) levels in the overall cohort, where median HDL-C was used as a reference and the HDL-C probability distribution histogram is represented in gray bars in the background. Dashed red lines represent 95% confidence intervals.
Tables
Characteristic Overall HDL-C≤25 mg/dl HDL-C>25 to <34 mg/dl HDL-C≥34 to ≤42 mg/dl HDL-C>42 to <50 mg/dl HDL-C≥50 mg/dl No. (%) 1,764,986 65,431 (3.7) 338,327 (19.2) 522,373 (29.6) 399,303 (22.6) 439,552 (24.9) Median HDL-C (IQR), mg/dl 41.0 (34.0–49.5) 23.0 (21.6–25.0) 30.0 (28.1–32.0) 37.9 (36.0–39.5) 45.0 (43.0–47.0) 57.0 (53.0–65.0) Race (%) White 1,503,312 (85.2) 58,598 (89.6) 299,469 (88.5) 452,934 (86.7) 338,073 (84.7) 354,238 (80.6) Black 224,785 (12.7) 5626 (8.6) 31,649 (9.4) 58,008 (11.1) 52,670 (13.2) 76,832 (17.5) Other 36,889 (2.1) 1207 (1.8) 7209 (2.1) 11,431 (2.2) 8560 (2.1) 8482 (1.9) Median age (IQR), yr 64.1 (56.1–72.6) 61.8 (55.1–71.4) 63.1 (55.7–72.0) 64.0 (56.1–72.4) 64.8 (56.3–72.9) 65.0 (56.3–73.1) Cancer (%) 248,058 (14.1) 9567 (14.6) 45,499 (13.5) 71,324 (13.7) 55,676 (13.9) 65,992 (15.0) Cerebrovascular accident (%) 11,633 (0.7) 613 (0.9) 2704 (0.8) 3643 (0.7) 2412 (0.6) 2261 (0.5) Coronary artery disease (%) 576,589 (32.7) 28,484 (43.5) 132,693 (39.2) 181,056 (34.7) 122,458 (30.7) 111,898 (25.5) Congestive heart failure (%) 146,203 (8.3) 10,055 (15.4) 37,141 (11.0) 44,195 (8.5) 28,235 (7.1) 26,577 (6.1) Chronic lung disease (%) 384,971 (21.8) 15,966 (24.4) 73,546 (21.7) 107,299 (20.5) 82,971 (20.8) 105,189 (23.9) Diabetes mellitus (%) 557,235 (31.6) 31,039 (47.4) 138,205 (40.9) 179,777 (34.4) 113,751 (28.5) 94,463 (21.5) Dementia (%) 61,308 (3.5) 2438 (3.7) 11,563 (3.4) 17,766 (3.4) 13,831 (3.5) 15,710 (3.6) HIV (%) 119,926 (6.8) 6277 (9.6) 26,114 (7.7) 35,227 (6.7) 25,030 (6.3) 27,278 (6.2) Hypertension (%) 1,278,661 (72.5) 50,986 (77.9) 258,782 (76.5) 385,445 (73.8) 283,880 (71.1) 299,568 (68.2) Hepatitis C (%) 81,256 (4.6) 5312 (8.1) 16,527 (4.9) 21,527 (4.1) 16,189 (4.1) 21,701 (4.9) Peripheral artery disease (%) 60,387 (3.4) 3302 (5.1) 14,210 (4.2) 18,337 (3.5) 12,246 (3.1) 12,292 (2.8) Average eGFR at T0 (SD), ml/min per 1.73 m2 74.8 (19.3) 71.7 (21.6) 72.6 (20.0) 73.9 (19.2) 75.2 (18.7) 77.7 (18.6) eGFR at T0 (%), ml/min per 1.73 m2 ≥90 25,249 (1.4) 2085 (3.2) 7150 (2.1) 7640 (1.5) 4462 (1.1) 3912 (0.9) ≥60 to <90 98,720 (5.6) 5972 (9.1) 25,157 (7.4) 31,263 (6.0) 19,746 (5.0) 16,582 (3.8) ≥45 to <60 272,441 (15.4) 11,479 (17.5) 57,977 (17.1) 85,344 (16.3) 60,612 (15.2) 57,029 (13.0) ≥30 to <45 954,680 (54.1) 31,176 (47.7) 176,095 (52.1) 283,942 (54.4) 222,440 (55.7) 241,027 (54.8) ≥15 to <30 413,896 (23.5) 14,719 (22.5) 71,948 (21.3) 114,184 (21.9) 92,043 (23.1) 121,002 (27.5) Dialysis during follow-up (%) 27,157 (1.5) 1727 (2.6) 6961 (2.1) 8144 (1.6) 5152 (1.3) 5173 (1.2) Kidney transplant during follow-up (%) 11,515 (0.7) 761 (1.2) 2897 (0.9) 3357 (0.6) 2175 (0.5) 2325 (0.5) Average LDL-C (SD), mg/dl 109.79 (33.8) 93.16 (33.9) 104.40 (33.3) 110.88 (33.6) 113.73 (33.6) 111.54 (33.5) Average triglycerides (SD), mg/dl 160.81 (114.3) 252.55 (194.2) 204.98 (132.5) 171.69 (108.0) 145.35 (94.2) 114.25 (78.3) Average serum albumin (SD), g/dl 4.09 (0.7) 3.88 (0.7) 4.00 (0.6) 4.08 (0.7) 4.13 (0.7) 4.16 (0.8) Body mass index (%) Underweight 17,671 (1.0) 378 (0.6) 1308 (0.4) 2604 (0.5) 3252 (0.8) 10,129 (2.3) Normal 345,569 (19.6) 8,507 (13.0) 41,815 (12.4) 78,388 (15.0) 79,063 (19.8) 137,796 (31.4) Overweight 689,296 (39.6) 23,492 (35.9) 126,130 (37.3) 207,027 (39.6) 167,046 (41.8) 179,755 (40.9) Obese 703,450 (39.9) 33,054 (50.5) 169,074 (50.0) 234,354 (44.9) 149,942 (37.6) 111,872 (25.5) Average body surface area (SD), m2 2.1 (0.2) 2.1 (0.2) 2.1 (0.2) 2.1 (0.2) 2.1 (0.2) 2.0 (0.2) Statin use during follow-up (%) 1,282,527 (72.7) 45,963 (70.3) 256,950 (76.0) 397,119 (76.0) 295,012 (73.9) 287,483 (65.4) ACEI/ARB use 876,615 (49.7) 38,709 (59.2) 189,971 (56.2) 270,522 (51.8) 189,658 (47.5) 187,755 (42.7) Median follow-up time (IQR), yr 9.1 (7.7–9.4) 9.1 (5.4–9.3) 9.1 (7.3–9.3) 9.1 (8.1–9.4) 9.2 (8.3–9.4) 9.1 (7.4–9.4) Death during follow-up (%) 541,682 (30.7) 26,247 (40.1) 109,222 (32.3) 152,625 (29.2) 113,785 (28.5) 139,803 (31.8) Microalbumin-to-creatinine ratio (%),a mg/g 0–<20 93,696 (69.8) 4133 (65.5) 21,558 (67.8) 30,232 (69.5) 20,322 (71.4) 17,451 (72.0) 20–<300 36,687 (27.3) 1902 (30.2) 9168 (28.9) 12,030 (27.6) 7429 (26.1) 6158 (25.4) ≥300 3938 (2.9) 272 (4.3) 1053 (3.3) 1264 (2.9) 709 (2.5) 640 (2.6) Average C–reactive proteinb (SD), mg/dl 2.0 (4.4) 2.4 (4.7) 2.2 (4.7) 2.0 (4.4) 1.9 (4.2) 1.9 (4.3) - Table 2.
Risk of all-cause mortality by HDL cholesterol levels in overall cohort and by eGFR category
eGFR, ml/min per 1.73 m2 Hazard Ratio (95% Confidence Interval) HDL-C≤25 mg/dl HDL-C>25 to <34 mg/dl HDL-C≥34 to ≤42 mg/dl HDL-C>42 to <50 mg/dl HDL-C≥50 mg/dl Overall 1.00 0.87 (0.86 to 0.88) 0.84 (0.83 to 0.85) 0.84 (0.82 to 0.85) 0.92 (0.91 to 0.93) ≥15 to <30 1.00 0.91 (0.86 to 0.96) 0.89 (0.84 to 0.94) 0.92 (0.86 to 0.97) 0.97 (0.91 to 1.03) ≥30 to <45 1.00 0.88 (0.85 to 0.91) 0.86 (0.83 to 0.89) 0.84 (0.81 to 0.87) 0.88 (0.85 to 0.92) ≥45 to <60 1.00 0.85 (0.83 to 0.88) 0.83 (0.80 to 0.85) 0.81 (0.79 to 0.84) 0.87 (0.85 to 0.89) ≥60 to <90 1.00 0.87 (0.85 to 0.89) 0.83 (0.82 to 0.85) 0.84 (0.82 to 0.86) 0.91 (0.89 to 0.93) ≥90 1.00 0.85 (0.83 to 0.88) 0.84 (0.82 to 0.87) 0.85 (0.82 to 0.88) 1.01 (0.97 to 1.04) Models were adjusted for age, race, cancer, cerebrovascular accident, chronic lung disease, diabetes mellitus, dementia, hepatitis C, HIV, hypertension, body mass index, LDL cholesterol, triglycerides, serum albumin, angiotensin–converting enzyme inhibitor/angiotensin receptor blocker use, coronary artery disease, congestive heart failure, and peripheral artery disease. Models were additionally adjusted for eGFR, dialysis, kidney transplant, and statin use as time varying. P for interaction of HDL-C and eGFR category is <0.01. HDL-C, HDL cholesterol.
HDL-C Decile Median (IQR) All-Cause Mortality Hazard Ratio (95% Confidence Interval) Overall eGFR≥15 to <30 ml/min per 1.73 m2 eGFR≥30 to <45 ml/min per 1.73 m2 eGFR≥45 to <60 ml/min per 1.73 m2 eGFR≥60 to <90 ml/min per 1.73 m2 eGFR≥90 ml/min per 1.73 m2 Decile 1 (low HDL-C) 27.0 (24.0–28.0) 1.00 1.00 1.00 1.00 1.00 1.00 Decile 2 32.0 (31.0–32.9) 0.92 (0.91 to 0.93) 0.92 (0.88 to 0.97) 0.94 (0.92 to 0.97) 0.90 (0.88 to 0.92) 0.93 (0.91 to 0.94) 0.92 (0.90 to 0.95) Decile 3 34.0 (34.0–35.0) 0.91 (0.90 to 0.93) 0.93 (0.88 to 0.99) 0.90 (0.87 to 0.93) 0.92 (0.90 to 095) 0.91 (0.89 to 0.93) 0.92 (0.89 to 0.95) Decile 4 37.0 (36.0–38.0) 0.91 (0.90 to 0.92) 0.91 (0.87 to 0.96) 0.92 (0.89 to 0.95) 0.89 (0.87. 0.91) 0.91 (0.89 to 0.92) 0.92 (0.89 to 0.94) Decile 5 40.0 (39.0–41.0) 0.90 (0.89 to 0.91) 0.91 (0.86 to 0.96) 0.94 (0.91 to 0.97) 0.88 (0.86 to 0.90) 0.89 (0.87 to 0.90) 0.91 (0.89 to 0.94) Decile 6 43.0 (42.0–44.0) 0.90 (0.89 to 0.91) 0.99 (0.94 to 1.05) 0.89 (0.86 to 0.92) 0.88 (0.86 to 0.90) 0.90 (0.89 to 0.92) 0.91 (0.88 to 0.94) Decile 7 46.0 (45.0–47.0) 0.91 (0.90 to 0.92) 0.89 (0.84 to 0.96) 0.92 (0.88 to 0.95) 0.89 (0.86 to 0.91) 0.91 (0.90 to 0.93) 0.92 (0.89 to 0.95) Decile 8 50.0 (48.9–51.0) 0.92 (0.91 to 0.93) 0.97 (0.91 to 1.03) 0.91 (0.87 to 0.94) 0.89 (0.86 to 0.91) 0.91 (0.90 to 0.93) 0.98 (0.95 to 1.01) Decile 9 56.0 (54.0–58.0) 0.94 (0.93 to 0.95) 0.95 (0.89 to 1.02) 0.95 (0.91 to 0.98) 0.90 (0.88 to 093) 0.93 (0.91 to 0.95) 1.01 (0.98 to 1.04) Decile 10 (high HDL-C) 68.1 (64.0–77.0) 1.09 (1.08 to 1.11) 1.07 (1.00 to 1.15) 0.99 (0.96 to 1.04) 1.01 (0.98 to 1.04) 1.08 (1.06 to 1.09) 1.22 (1.18 to 1.25) Models were adjusted for age, race, cancer, cerebrovascular accident, chronic lung disease, diabetes mellitus, dementia, hepatitis C, HIV, hypertension, body mass index, LDL cholesterol, triglycerides, serum albumin, angiotensin–converting enzyme inhibitor/angiotensin receptor blocker use, coronary artery disease, congestive heart failure, and peripheral artery disease. Models were additionally adjusted for eGFR, dialysis, kidney transplant, and statin use as time varying. IQR, interquartile range; HDL-C, HDL cholesterol.
- Table 4.
Effect modification of the relationship between HDL cholesterol and risk of death by presence of coronary artery disease
eGFR (ml/min per 1.73 m2) with or without Coronary Artery Disease Hazard Ratio (95% Confidence Interval) HDL-C≤25 mg/dl HDL-C>25 to <34 mg/dl HDL-C≥34 to ≤42 mg/dl HDL-C>42 to <50 mg/dl HDL-C≥50 mg/dl ≥15 to <30 Without 1.00 0.92 (0.83 to 1.02) 0.92 (0.83 to 1.02) 0.96 (0.86 to 1.07) 0.97 (0.87 to 1.09) With 1.00 0.91 (0.85 to 0.97) 0.88 (0.82 to 0.93) 0.89 (0.83 to 0.96) 0.98 (0.91 to 1.05) ≥30 to <45 Without 1.00 0.84 (0.79 to 0.89) 0.82 (0.77 to 0.87) 0.81 (0.76 to 0.86) 0.85 (0.80 to 0.91) With 1.00 0.90 (0.86 to 0.93) 0.87 (0.84 to 0.91) 0.85 (0.81 to 0.89) 0.89 (0.85 to 0.93) ≥45 to <60 Without 1.00 0.84 (0.80 to 0.88) 0.81 (0.77 to 0.84) 0.80 (0.77 to 0.84) 0.85 (0.81 to 0.89) With 1.00 0.86 (0.83 to 0.89) 0.84 (0.81 to 0.87) 0.82 (0.79 to 0.85) 0.88 (0.85 to 0.92) ≥60 to <90 Without 1.00 0.84 (0.82 to 0.87) 0.80 (0.78 to 0.83) 0.81 (0.79 to 0.84) 0.88 (0.86 to 0.91) With 1.00 0.89a (0.87 to 0.92) 0.86a (0.84 to 0.89) 0.87a (0.84 to 0.89) 0.93a (0.90 to 0.96) ≥90 Without 1.00 0.81 (0.78 to 0.85) 0.80 (0.77 to 0.83) 0.80 (0.77 to 0.84) 0.96 (0.92 to 1.00) With 1.00 0.93a (0.87 to 0.98) 0.92a (0.87 to 0.98) 0.94a (0.88 to 0.99) 1.08a (1.02 to 1.14) Models were adjusted for age, race, cancer, cerebrovascular accident, chronic lung disease, diabetes mellitus, dementia, hepatitis C, HIV, hypertension, body mass index, LDL cholesterol, triglycerides, serum albumin, angiotensin–converting enzyme inhibitor/angiotensin receptor blocker use, coronary artery disease, congestive heart failure, and peripheral artery disease. Models were additionally adjusted for eGFR, dialysis, kidney transplant, and statin use as time varying. HDL-C, HDL cholesterol.
↵a Significant (<0.05) P value for interaction between HDL-C level and coronary artery disease status.
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