Evidence mapPaperPMID 39358768Full record

Observational studyLipids in health and disease2024

Association between lipid-lowering agents with intervertebral disc degeneration, sciatica and low back pain: a drug-targeted mendelian randomized study and cross-sectional observation.

Chenxu Liu, Xinqiao Chu, Yaning Biao, Qiubai Jin, Yufang Zhang, Ya Gao, Shuo Feng, Jizheng Ma, Yixin Zhang

Abstract readObservational Study
In one paragraph

Observational study in Lipids in health and disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Chenxu Liu *School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.
Xinqiao Chu *Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5, Beixian Pavilion, Xicheng District, Beijing, 100053, China.
Yaning BiaoSchool of Pharmacy, Hebei University of Chinese Medicine, 326 New Shinan Road, Qiaoxi District, Shijiazhuang, Hebei, 050017, China.
Qiubai JinGuang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5, Beixian Pavilion, Xicheng District, Beijing, 100053, China.
Yufang ZhangSchool of Pharmacy, Hebei University of Chinese Medicine, 326 New Shinan Road, Qiaoxi District, Shijiazhuang, Hebei, 050017, China.
Ya GaoSchool of Pharmacy, Hebei University of Chinese Medicine, 326 New Shinan Road, Qiaoxi District, Shijiazhuang, Hebei, 050017, China.
Shuo FengGuang'anmen Hospital South Campus, China Academy of Chinese Medical Sciences, Beijing, China.
Jizheng MaGuang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5, Beixian Pavilion, Xicheng District, Beijing, 100053, China. majizheng1116@yeah.net.
Yixin ZhangSchool of Pharmacy, Hebei University of Chinese Medicine, 326 New Shinan Road, Qiaoxi District, Shijiazhuang, Hebei, 050017, China. hbzyx123@163.com.

Funding

Beijing Traditional Chinese Medicine Science and Technology Development Funding Programme No.JJ-2023-115Key Project of Natural Science Foundation of Hebei Province No.H2023423064Science and Technology Innovation Project of China Academy of Chinese Medical Sciences No. CI2021A02306Young Scientists Fund Project of National Natural Science Foundation of China No.82003913
6 · The paper itself

Abstract

backgroundAbnormal lipid metabolism is linked to intervertebral disc degeneration (IVDD), sciatica, and low back pain (LBP), but it remains unclear whether targeted interventions can prevent these issues. This study investigated the causal effects of lipid-lowering drug use on IVDD, sciatica, and LBP development.

methodsSingle-nucleotide polymorphisms (SNPs) linked to total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and non-high-density-lipoprotein cholesterol (non-HDL-C) were obtained from the Global Lipids Genetics Consortium's genome-wide association study (GWAS). Genes near HMGCR, PCSK9, and NPC1L1 were selected to represent therapeutic inhibition targets. Using Mendelian randomization (MR) focusing on these drug targets, we identified causal effects of PCSK9, HMGCR, and NPC1L1 on the risk of developing IVDD, sciatica, and LBP, with coronary heart disease risk serving as a positive control. Using summary data from Mendelian randomization (SMR) analysis, we evaluated potential therapeutic targets for IVDD, sciatica, and LBP through protein quantitative trait loci (pQTL). The genetic associations with IVDD, sciatica, LBP, and coronary heart disease were derived from FinnGen (discovery) and UK Biobank (replication). Additionally, a cross-sectional observational study was performed using data from the National Health and Nutrition Examination Survey (NHANES) to further investigate the connection between LBP and statin use, with a sample size of 4343 participants. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to assess the outcomes.

resultsThe NHANES-based cross-sectional study indicated that non-statin use was associated with an increased risk of developing LBP (OR = 1.29, 95% CI [1.04, 1.59], P = 0.019). Moreover, Inverse-variance weighting (IVW) analysis revealed that NPC1L1-mediated reductions in TC, LDL-C, and non-HDL-C concentrations were associated with a decreased risk of developing IVDD (P = 9.956E-03; P = 3.516E-02; P = 1.253E-04). Similarly, PCSK9-mediated reductions in LDL-C and TC concentrations were linked to a lower risk of developing sciatica (P = 3.825E-02; P = 2.709E-02). Sensitivity analysis confirmed the stability and reliability of the MR results. MST1 (macrophage stimulating 1) levels was inversely associated with IVDD, sciatica, and LBP risks.

conclusionThe results of cross-sectional study suggested that non-use of statins was positively correlated with LBP. The results of Mendelian randomization study suggest that NPC1L1 could lower the risk of developing IVDD by reducing TC, LDL-C, and non-HDL-C levels. Additionally, PCSK9 may reduce the risk of developing sciatica by lowering LDL-C and TC levels. In contrast, HMGCR appears to have no significant effect on IVDD, sciatica, or LBP development. Nonetheless, further research is needed to verify these preliminary results. MST1 warrants further exploration as a potential therapeutic target. It is necessary to do further research to validate these findings.

Indexed as

Genome-Wide Association StudyHydroxymethylglutaryl CoA ReductasesIntervertebral Disc DegenerationLow Back PainMendelian Randomization AnalysisPolymorphism, Single NucleotideProprotein Convertase 9SciaticaAdultCholesterol, LDLCross-Sectional StudiesFemaleHumansHypolipidemic AgentsMaleMembrane ProteinsCholesterol, LDLHMGCR protein, humanHydroxymethylglutaryl CoA ReductasesHypolipidemic AgentsMembrane ProteinsMembrane Transport ProteinsNPC1L1 protein, humanPCSK9 protein, humanProprotein Convertase 9Intervertebral disc disordersLipid-lowering drugsLow back painMendelian randomizationObservational studySciatica

Identifiers

PMID39358768
PMCPMC11445963

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.