Premorbid lipid levels and long-term risk of ALS—a population-based cohort study

Figures & data

Figure 1. Selection of participants. CONOR, Cohort of Norway; HDL-C, high-density lipoprotein cholesterol.

Table 1. Baseline characteristics of the cohort.

	Entire cohort	No ALS	ALS	p Value
Participants, n	640,066	639,092	974
Age	42.6 (9.1)	42.6 (9.1)	44.2 (8.8)	<.001*
Female	329,607 (51.5%)	329,183 (51.5%)	424 (43.5%)	<.001*
Observation years	27.0 (8.0)	27.1 (8.0)	23.7 (7.1)	<.001*
Birth year	1948 (10.5)	1948 (10.5)	1944 (10)	<.001*
BMI (n = 638,035)	25.2 (3.8)	25.2 (3.8)	25.1 (3.5)	.392*
Current smoker^a (n = 575,291)	221,791 (38.6%)	221,448 (38.6%)	343 (37.3%)	.428**
Stroke^a (n = 637,626)	3,816 (0.6%)	3,811 (0.6%)	5 (0.5%)	.736**
Heart attack^a (n = 637,903)	5,848 (0.9%)	5,839 (0.9%)	9 (0.9%)	.976**
Diabetes^a (n = 637,711)	7,773 (1.2%)	7,767 (1.2%)	6 (0.6%)	.088**
Higher education^a (college, university, PhD) (n = 299,471)	91,328 (30.5 %)	91,220 (30.5 %)	108 (29.6 %)	.706**
Physical activity^a (n = 467,409)				.839**
Inactive	94,489 (20.2%)	94,333 (20.2%)	156 (20.5%)
Light activity	283,699 (60.7%)	283,246 (60.7%)	453 (59.5%)
Exercises regularly	80,323 (17.2%)	80,187 (17.2%)	136 (17.9%)
Strenuous activity	8,898 (1.9%)	8,881 (1.9%)	17 (2.2%)
Exposure variables
Total cholesterol in mmol/l N (n missing)	5.8 (1.2) 626,538 (13,528)	5.8 (1.2) 625,583 (13,509)	6.0 (1.1) 955 (19)	<.001*
Triglycerides in mmol/l N (n missing)	1.7 (1.2) 626,534 (13,532)	1.7 (1.2) 625,579 (13,513)	1.9 (1.4) 955 (19)	<.001*
HDL-C in mmol/l N (n missing)	1.4 (0.4) 365,673 (274,393)	1.4 (0.4) 365,114 (273,978)	1.4 (0.4) 559 (415)	.996*
LDL-C in mmol/l N (n missing)	3.7 (1.1) 353,716 (286,350)	3.7 (1.1) 353,174 (285,918)	3.9 (1.1) 542 (432)	<.001*
Glucose in mmol/l N (n missing)	5.4 (1.3) 332,448 (307,618)	5.4 (1.3) 331,956 (307,136)	5.6 (1.1) 492 (482)	.009*

Data are shown as mean (standard deviation) for continuous variables, or n (%) for categorical variables.

BMI, body mass index; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol.

*Independent samples t-test.

**χ²-test.

^aInformation on smoking status, stroke, diabetes, heart attack, levels of physical activity, and education were self-reported.

Figure 2. Risk (HR) of amyotrophic lateral sclerosis (ALS), according to increasing levels of lipid biomarkers and time since blood sampling, adjusted for sex, age, birth cohort, health survey, other lipids, BMI, physical activity, and smoking. LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol.

Table 2. Risk of amyotrophic lateral sclerosis (ALS) for one-unit (mmol/l) increase in premorbid levels of circulating lipids.

Parameters	Model 1a		Model 1b		Model 2a		Model 2b
	RC (SE)	p Value	RC (SE)	p Value	RC (SE)	p Value	RC (SE)	p Value
LDL-C	—	—	0.06 (0.03)	.034	—	—	0.07 (0.02)	.007
Total cholesterol	0.26 (0.05)	<.001	—	—	0.17 (0.05)	<.001	—	—
Total cholesterol × ln(t)	−0.09 (0.03)	.001	—	—	−0.04 (0.02)	.043	—	—
Triglycerides	0.22 (0.08)	.004	0.32 (0.05)	<.001	0.25 (0.04)	<.001	0.32 (0.05)	<.001
Triglycerides × ln(t)	−0.07 (0.04)	.048	−0.10 (0.03)	<.001	−0.09 (0.03)	.001	−0.11 (0.03)	<.001
HDL-C	−0.06 (0.17)	.702	−0.09 (0.25)	.719	−0.06 (0.26)	.805	0.00 (0.25)	.999

Cox proportional hazard models with normalized inverse probability weights, generated from sample of 640,066 study participants. Model 1 adjusted for sex, age, and health survey. Model 2 adjusted for sex, age, birth cohort, health survey, other lipids, BMI, physical activity, and smoking status. Due to high correlation, total cholesterol and LDL-C were assessed in separate models (a and b).

RC, regression coefficient; SE, standard error; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol, ln(t), the natural logarithm of observation time; BMI, body mass index.

p-values marked in bold are statistically significant.

Data availability

The authors do not have permission to share data.