Relationship between Total Cholesterol Burden and Newly Developed Peripheral Artery Disease

doi:10.3969/j.issn.1673-5765.2023.05.008

Abstract

Abstract: Objective To investigate the relationship between TC burden and newly developed peripheral artery disease (PAD) .
Methods In the asymptomatic polyvascular abnormalities community (APAC) study, the participants (were followed-up every 2 years from 2006 to 2012. The TC was measured at each follow-up. TC burden was calculated as the weighted sum of the difference between measured value and cutoff value. Ankle-brachial index (ABI) measurements were completed at the third and fourth follow-up, and unilateral or bilateral lower extremity ABI<0.90 indicates that PAD exists. Participants were divided into four groups according to the TC burden quartile, and the relationship between TC burden and PAD was evaluated by logistic regression.
Results Of the 2939 participants, 159 (5.4%) had newly developed PAD. In univariate analysis, increased TC burden was not significantly associated with new PAD compared to the lowest quartile group (Q1) (OR 1.109, 95%CI 0.961-1.280, P=0.157) . After adjusting for confounding factors, there was still no significant correlation between TC burden and new PAD (OR 1.062, 95%CI 0.916-1.232, P=0.346) . Among the four groups, participants in the second quartile (Q2) had the lowest incidence of new PAD. Compared with Q2, participants in Q1 and the highest quartile (Q4) group as a whole had an increased risk of new PAD (Q4 group was not statistically significant after excluding participants aged 65 years or older) , while participants in the third quartile (Q3) were not statistically significant.
Conclusions There is no significant linear correlation between TC burden and newly developed PAD, but long-term high or low TC level may increase the risk of newly developed PAD.

Key words: Total cholesterol burden; Peripheral artery disease; Ankle-brachial index

摘要： 目的探讨总胆固醇负荷（TC负荷）与新发外周动脉疾病（peripheral artery disease，PAD）的关系。
方法在开滦队列研究的子队列即无症状性多血管异常社区研究中，2006—2012年每2年对参与者进行随访，每次随访时进行TC测定，TC负荷定义为测量值和临界值之差的加权和。在第3次和第4次随访时完成踝臂指数（ankle-brachial index，ABI）测量，单侧或双侧下肢ABI＜0.90认为存在PAD。根据TC负荷四分位数将参与者分为4组，并通过logistic回归评估TC负荷与PAD之间的关系。
结果本研究共纳入2939例参与者，其中159例（5.4%）合并新发PAD。在单因素分析中，与最低四分位数（Q1）组相比，TC负荷升高与新发PAD无相关（OR 1.109，95%CI 0.961～1.280，P=0.157），且校正混杂因素后TC负荷与新发PAD仍无相关（OR 1.062，95%CI 0.916～1.232，P=0.346）。在4组参与者中，第2四分位数（Q2）组的参与者新发PAD的发生率最低，与Q2组相比，Q1组及最高四分位数（Q4）组整体参与者新发PAD风险升高（剔除年龄≥65岁的参与者后Q4组差异无统计学意义），而与第3四分位数（Q3）组参与者的差异不具有统计学意义。
结论 TC负荷与新发PAD不存在显著的线性相关性，但长期TC水平过高或过低可能会增加新发PAD风险。

关键词: 总胆固醇负荷; 外周动脉疾病; 踝臂指数

ZHANG Lei, WU Jianwei, KANG Kaijiang, ZHAO Xingquan.

Relationship between Total Cholesterol Burden and Newly Developed Peripheral Artery Disease

[J]. Chinese Journal of Stroke, 2023, 18(05): 538-546.

张磊, 吴建维, 康开江, 赵性泉. 总胆固醇负荷与新发外周动脉疾病的关系研究[J]. 中国卒中杂志, 2023, 18(05): 538-546.

References

[1] CRIQUI M H，ABOYANS V. Epidemiology of peripheral artery disease[J]. Circul Res，2015，116（9）：1509-1526.
[2] MORLEY R L，SHARMA A，HORSCH A D，et al. Peripheral artery disease[J/OL]. BMJ，2018，360：j5842[2022-06-08]. https://doi.org/10.1136/bmj.j5842.
[3] CICERO A F G，SALVETTI M. Peripheral artery disease：a highly prevalent untreated and uncontrolled independent cardiovascular disease[J/OL]. Atherosclerosis，2022，354：55-56[2022-06-08]. https://doi.org/10.1016/j.atherosclerosis.2022.06.1015.
[4] VOLIS I，SALIBA W，JAFFE R，et al. Effect of cerebrovascular and/or peripheral artery disease with or without attainment of lipid goals on long-term outcomes in patients with coronary artery disease[J/OL]. Am J Cardiol，2020，128：28-34[2022-06-08]. https://doi.org/10.1016/j.amjcard.2020.04.043.
[5] BONACA M P，NAULT P，GIUGLIANO R P，et al. Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease：insights from the FOURIER trial（further cardiovascular outcomes research with PCSK9 inhibition in subjects with elevated risk）[J]. Circulation，2018，137（4）：338-350.
[6] PARVAR S L，FITRIDGE R，DAWSON J，et al. Medical and lifestyle management of peripheral arterial disease[J]. J Vasc Surg，2018，68（5）：1595-1606.
[7] FOWKES F G R，RUDAN D，RUDAN I，et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010：a systematic review and analysis[J]. Lancet，2013，382（9901）：1329-1340.
[8] SUNDBØLL J，LARSEN A P，VERES K，et al. Cardiovascular event rates and trajectories of LDL-cholesterol levels and lipid-lowering therapy in patients with atherosclerotic cardiovascular disease：a population-based cohort study[J/OL]. Thromb Res，2019，183：124-130[2022-06-08]. https://doi.org/10.1016/j.thromres.2019.09.034.
[9] ADAY A W，LAWLER P R，COOK N R，et al. Lipoprotein particle profiles，standard lipids，and peripheral artery disease incidence[J]. Circulation，2018，138（21）：2330-2341.
[10] RIDKER P M，STAMPFER M J，RIFAI N. Novel risk factors for systemic atherosclerosis：a comparison of C-reactive protein，fibrinogen，homocysteine，lipoprotein（a），and standard cholesterol screening as predictors of peripheral arterial disease[J]. JAMA，2001，285（19）：2481-2485.
[11] KENNEDY M，SOLOMON C，MANOLIO T A，et al. Risk factors for declining ankle-brachial index in men and women 65 years or older：the cardiovascular health study[J]. Arch Intern Med，2005，165（16）：1896-1902.
[12] ZIERFUSS B，HÖBAUS C，FELDSCHER A，et al. Lipoprotein（a）and long-term outcome in patients with peripheral artery disease undergoing revascularization[J/OL]. Atherosclerosis，2022，363：94-101[2022-06-08]. https://doi.org/10.1016/j.atherosclerosis.2022.10.002.
[13] SMOLDEREN K G，ALABI O，COLLINS T C，et al. Advancing peripheral artery disease quality of care and outcomes through patient-reported health status assessment：a scientific statement from the American Heart Association[J/OL]. Circulation，2022，146（20）：e286-e297[2022-06-08]. https://doi.org/10.1161/CIR.0000000000001105.
[14] LIU X M，WANG Y，WU J W，et al. Association between cumulative exposure to increased low-density lipoprotein cholesterol and the new occurrence of peripheral artery disease[J/OL]. Front Neurol，2021，12：696695[2022-06-08]. https://doi.org/10.3389/fneur.2021.696695.
[15] ZHOU Y，LI Y，XU L，et al. Asymptomatic polyvascular abnormalities in community（APAC） study in China：objectives，design and baseline characteristics[J/OL]. PLoS One，2013，8（12）：e84685[2022-06-08]. https://doi.org/10.1371/journal.pone.0084685.
[16] WU S L，HUANG Z R，YANG X C，et al. Prevalence of ideal cardiovascular health and its relationship with the 4-year cardiovascular events in a northern Chinese industrial city[J]. Circ Cardiovasc Qual Outcomes，2012，5（4）：487-493.
[17]National Cholesterol Education Program（NCEP） Expert Panel on Detection，Evaluation，and Treatment of High Blood Cholesterol in Adults（Adult Treatment Panel Ⅲ）. Third report of the National Cholesterol Education Program（NCEP）expert panel on detection，evaluation，and treatment of high blood cholesterol in adults（adult treatment panel Ⅲ） final report[J]. Circulation，2002，106（25）：3143-3421.
[18] PRADHAN A D，SHRIVASTAVA S，COOK N R，et al. Symptomatic peripheral arterial disease in women：nontraditional biomarkers of elevated risk[J]. Circulation，2008，117（6）：823-831.
[19] BANSAL S，BURING J E，RIFAI N，et al. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women[J]. JAMA，2007，298（3）：309-316.
[20] ISO H，NAITO Y，SATO S，et al. Serum triglycerides and risk of coronary heart disease among Japanese men and women[J]. Am J Epidemiol，2001，153（5）：490-499.
[21] MORA S，RIFAI N，BURING J E，et al. Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events[J]. Circulation，2008，18（10）：993-1001.
[22] NORDESTGAARD B G，BENN M，SCHNOHR P，et al. Nonfasting triglycerides and risk of myocardial infarction，ischemic heart disease，and death in men and women[J]. JAMA，2007，298（3）：299-308.
[23] JACOBS D，BLACKBURN H，HIGGINS M，et al. Report of the conference on low blood cholesterol：mortality associations[J]. Circulation，1992，86（3）：1046-1060.
[24] FEINGOLD K R，FUNK J L，MOSER A H，et al. Role for circulating lipoproteins in protection from endotoxin toxicity[J]. Infect Immun，1995，63（5）：2041-2046.
[25] SAENZ-PIPAON G，MARTINEZ-AGUILAR E，ORBE J，et al. The role of circulating biomarkers in peripheral arterial disease[J/OL]. Int J Mol Sci，2021，22（7）：3601[2022-06-08]. https://doi.org/10.3390/ijms22073601.