{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:35:28Z","timestamp":1790411728801,"version":"4.1.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Proprotein convertase subtilisin\/kexin type 9 (PCSK9) circulating levels are significantly associated with an increased risk of cardiovascular events. This study aimed to evaluate the relationship between circulating levels of\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">PCSK<\/jats:styled-content>\n              9 and arterial stiffness, an early instrumental biomarker of cardiovascular disease risk, in a large sample of overall healthy participants.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              From the historical cohort of the Brisighella Heart Study, after exclusion of active smokers, participants in secondary prevention for cardiovascular disease, and patients in treatment with statins or vasodilating agents, we selected 227 premenopausal women and 193 age\u2010matched men and 460 postmenopausal women and 416 age\u2010matched men. In these participants, we evaluated the correlation between\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">PCSK<\/jats:styled-content>\n              9 plasma circulating levels and pulse wave velocity. Postmenopausal women showed higher\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">PCSK<\/jats:styled-content>\n              9 levels (309.9\u00b184.1\u00a0ng\/mL) compared with the other groups (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001). Older men had significant higher levels than younger men (283.2\u00b175.6\u00a0versus 260.9\u00b180.4\u00a0ng\/mL;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.008). In the whole sample, pulse wave velocity was predicted mainly by age (B=0.116, 95%\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">CI<\/jats:styled-content>\n              0.96\u20130.127,\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001),\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">PCSK<\/jats:styled-content>\n              9 (B=0.014, 95%\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">CI<\/jats:styled-content>\n              0.011\u20130.016,\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001), and serum uric acid (B=0.313, 95%\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">CI<\/jats:styled-content>\n              0.024\u20130.391,\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.026). Physical activity, low\u2010density lipoprotein cholesterol, high\u2010density lipoprotein cholesterol, and estimated glomerular filtration rate were not associated with pulse wave velocity (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &gt;0.05).By considering the subgroups described, age and\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">PCSK<\/jats:styled-content>\n              9 levels were mainly associated with pulse wave velocity, which also correlated with serum uric acid in postmenopausal women.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In the Brisighella Heart Study cohort, circulating\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">PCSK<\/jats:styled-content>\n              9 is significantly related to arterial stiffness, independent of sex and menopausal status in women.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.005764","type":"journal-article","created":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T20:10:32Z","timestamp":1493842232000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":71,"title":["Circulating Levels of Proprotein Convertase Subtilisin\/Kexin Type 9 and Arterial Stiffness in a Large Population Sample: Data From the Brisighella Heart Study"],"prefix":"10.1161","volume":"6","author":[{"given":"Massimiliano","family":"Ruscica","sequence":"first","affiliation":[{"name":"Universit\u00e0 degli Studi di Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Ferri","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi di Padova","place":["Padua, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Fogacci","sequence":"additional","affiliation":[{"name":"University of Bologna","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Rosticci","sequence":"additional","affiliation":[{"name":"University of Bologna","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Botta","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi di Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Marchiano","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi di Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Magni","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi di Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"D'Addato","sequence":"additional","affiliation":[{"name":"University of Bologna","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Giovannini","sequence":"additional","affiliation":[{"name":"University of Bologna","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Borghi","sequence":"additional","affiliation":[{"name":"University of Bologna","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arrigo F. G.","family":"Cicero","sequence":"additional","affiliation":[{"name":"University of Bologna","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martino","family":"Morbini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Bertagnin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Grandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Palmesano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Rizzoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Urso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Derosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Bacchelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.trsl.2015.10.004","article-title":"Proprotein convertase subtilisinkexin type 9 and high\u2010density lipoprotein metabolism: experimental animal models and clinical evidence","volume":"173","author":"Ferri N","year":"2016","unstructured":"Ferri N, Corsini A, Macchi C, Magni P, Ruscica M. Proprotein convertase subtilisinkexin type 9 and high\u2010density lipoprotein metabolism: experimental animal models and clinical evidence. Transl Res. 2016;173:19\u201329.","journal-title":"Transl Res"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1194\/jlr.R026658","article-title":"The PCSK9 decade","volume":"53","author":"Lambert G","year":"2012","unstructured":"Lambert G, Sjouke B, Choque B, Kastelein JJ, Hovingh GK. The PCSK9 decade. J Lipid Res. 2012;53:2515\u20132524.","journal-title":"J Lipid Res"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1093\/cvr\/cvw194","article-title":"Biology of proprotein convertase subtilisinkexin 9: beyond low\u2010density lipoprotein cholesterol lowering","volume":"112","author":"Norata GD","year":"2016","unstructured":"Norata GD, Tavori H, Pirillo A, Fazio S, Catapano AL. Biology of proprotein convertase subtilisinkexin 9: beyond low\u2010density lipoprotein cholesterol lowering. Cardiovasc Res. 2016;112:429\u2013442.","journal-title":"Cardiovasc Res"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1161\/ATVBAHA.110.220988","article-title":"Circulating proprotein convertase subtilisin\/kexin 9 (PCSK9) regulates VLDLR protein and triglyceride accumulationin visceral adipose tissue","volume":"31","author":"Roubtsova A","year":"2011","unstructured":"Roubtsova A, Munkonda MN, Awan Z, Marcinkiewicz J, Chamberland A, Lazure C, Cianflone K, Seidah NG, Prat A. Circulating proprotein convertase subtilisin\/kexin 9 (PCSK9) regulates VLDLR protein and triglyceride accumulationin visceral adipose tissue. Arterioscler Thromb Vasc Biol. 2011;31:785\u2013791.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1007\/s12020-016-0939-0","article-title":"Proprotein convertase subtilisin\/kexin type 9 (PCSK9) and metabolic syndrome: insights on insulin resistance, inflammation, and atherogenic dyslipidemia","volume":"54","author":"Ferri N","year":"2016","unstructured":"Ferri N, Ruscica M. Proprotein convertase subtilisin\/kexin type 9 (PCSK9) and metabolic syndrome: insights on insulin resistance, inflammation, and atherogenic dyslipidemia. Endocrine. 2016;54:588\u2013601.","journal-title":"Endocrine"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.atherosclerosis.2011.11.026","article-title":"Proprotein convertase subtilisinkexin type 9 (PCSK9) secreted by cultured smooth muscle cells reduces macrophages LDLR levels","volume":"220","author":"Ferri N","year":"2012","unstructured":"Ferri N, Tibolla G, Pirillo A, Cipollone F, Mezzetti A, Pacia S, Corsini A, Catapano AL. Proprotein convertase subtilisinkexin type 9 (PCSK9) secreted by cultured smooth muscle cells reduces macrophages LDLR levels. Atherosclerosis. 2012;220:381\u2013386.","journal-title":"Atherosclerosis"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.atherosclerosis.2016.07.910","article-title":"PCSK9 knock\u2010out mice are protected from neointimal formation in response to perivascular carotid collar placement","volume":"253","author":"Ferri N","year":"2016","unstructured":"Ferri N, Marchian\u00f2 S, Tibolla G, Baetta R, Dhyani A, Ruscica M, Uboldi P, Catapano AL, Corsini A. PCSK9 knock\u2010out mice are protected from neointimal formation in response to perivascular carotid collar placement. Atherosclerosis. 2016;253:214\u2013224.","journal-title":"Atherosclerosis"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ijcard.2016.04.103","article-title":"Association between plasma PCSK9 levels and 10\u2010year progression of carotid atherosclerosis beyond LDL\u2010C: a cohort study","volume":"215","author":"Xie W","year":"2016","unstructured":"Xie W, Liu J, Wang W, Wang M, Qi Y, Zhao F, Sun J, Liu J, Li Y, Zhao D. Association between plasma PCSK9 levels and 10\u2010year progression of carotid atherosclerosis beyond LDL\u2010C: a cohort study. Int J Cardiol. 2016;215:293\u2013298.","journal-title":"Int J Cardiol"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1194\/jlr.P023994","article-title":"Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia","volume":"53","author":"Huijgen R","year":"2012","unstructured":"Huijgen R, Fouchier SW, Denoun M, Hutten BA, Vissers MN, Lambert G, Kastelein JJ. Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia. J Lipid Res. 2012;53:979\u2013983.","journal-title":"J Lipid Res"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.metabol.2013.01.005","article-title":"Association of serum proprotein convertase subtilisin\/kexin type 9 with carotid intima media thickness in hypertensive subjects","volume":"62","author":"Lee CJ","year":"2013","unstructured":"Lee CJ, Lee YH, Park SW, Kim KJ, Park S, Youn JC, Lee SH, Kang SM, Jang Y. Association of serum proprotein convertase subtilisin\/kexin type 9 with carotid intima media thickness in hypertensive subjects. Metabolism. 2013;62:845\u2013850.","journal-title":"Metabolism"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1161\/CIRCULATIONAHA.109.914507","article-title":"Hemodynamic correlates of blood pressure across the adult age spectrum: noninvasive evaluation in the Framingham Heart Study","volume":"122","author":"Mitchell GF","year":"2010","unstructured":"Mitchell GF, Wang N, Palmisano JN, Larson MG, Hamburg NM, Vita JA, Levy D, Benjamin EJ, Vasan RS. Hemodynamic correlates of blood pressure across the adult age spectrum: noninvasive evaluation in the Framingham Heart Study. Circulation. 2010;122:1379\u20131386.","journal-title":"Circulation"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.atherosclerosis.2015.09.008","article-title":"A systematic literature review of the effect of carotid atherosclerosis on local vessel stiffness and elasticity","volume":"243","author":"Boesen ME","year":"2015","unstructured":"Boesen ME, Singh D, Menon BK, Frayne R. A systematic literature review of the effect of carotid atherosclerosis on local vessel stiffness and elasticity. Atherosclerosis. 2015;243:211\u2013222.","journal-title":"Atherosclerosis"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1080\/07853890.2016.1222451","article-title":"Serum uric acid change and modification of blood pressure and fasting plasma glucose in an overall healthy population sample: data from the Brisighella Heart Study","volume":"49","author":"Cicero AF","year":"2017","unstructured":"Cicero AF, Rosticci M, Bove M, Fogacci F, Giovannini M, Urso R, D'Addato S, Borghi C; Brisighella Heart Study Group . Serum uric acid change and modification of blood pressure and fasting plasma glucose in an overall healthy population sample: data from the Brisighella Heart Study. Ann Med. 2017;49:275\u2013282.","journal-title":"Ann Med"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/HJH.0b013e328365b916","article-title":"Association between serum uric acid, hypertension, vascular stiffness and subclinical atherosclerosis: data from the Brisighella Heart Study","volume":"32","author":"Cicero AF","year":"2014","unstructured":"Cicero AF, Salvi P, D'Addato S, Rosticci M, Borghi C; Brisighella Heart Study Group . Association between serum uric acid, hypertension, vascular stiffness and subclinical atherosclerosis: data from the Brisighella Heart Study. J Hypertens. 2014;32:57\u201364.","journal-title":"J Hypertens"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2459\/JCM.0b013e3283516798","article-title":"Leisure\u2010time physical activity and cardiovascular disease mortality: the Brisighella Heart Study","volume":"13","author":"Cicero AF","year":"2012","unstructured":"Cicero AF, D'Addato S, Santi F, Ferroni A, Borghi C; for the Brisighella Heart Study . Leisure\u2010time physical activity and cardiovascular disease mortality: the Brisighella Heart Study. J Cardiovasc Med. 2012;13:559\u2013564.","journal-title":"J Cardiovasc Med"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ejim.2016.07.026","article-title":"High serum uric acid is associated to poorly controlled blood pressure and higher arterial stiffness in hypertensive subjects","volume":"37","author":"Cicero AF","year":"2017","unstructured":"Cicero AF, Rosticci M, Fogacci F, Grandi E, D'Addato S, Borghi C; Brisighella Heart Study Group . High serum uric acid is associated to poorly controlled blood pressure and higher arterial stiffness in hypertensive subjects. Eur J Intern Med. 2017;37:38\u201342.","journal-title":"Eur J Intern Med"},{"key":"e_1_3_2_18_2","first-page":"1","article-title":"KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"3","author":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group","year":"2013","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group . KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1\u2013150.","journal-title":"Kidney Int Suppl"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1097\/00004872-200305000-00001","article-title":"European Society of Hypertension recommendations for conventional, ambulatory and home blood pressure measurement","volume":"21","author":"O'Brien E","year":"2003","unstructured":"O'Brien E, Asmar R, Beilin L, Imai Y, Mallion JM, Mancia G, Mengden T, Myers M, Padfield P, Palatini P, Parati G, Pickering T, Redon J, Staessen J, Stergiou G, Verdecchia P; European Society of Hypertension Working Group on Blood Pressure Monitoring . European Society of Hypertension recommendations for conventional, ambulatory and home blood pressure measurement. J Hypertens. 2003;21:821\u2013848.","journal-title":"J Hypertens"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1080\/07853890.2016.1188328","article-title":"Liver fat accumulation is associated with circulating PCSK9","volume":"48","author":"Ruscica M","year":"2016","unstructured":"Ruscica M, Ferri N, Macchi C, Meroni M, Lanti C, Ricci C, Maggioni M, Fracanzani AL, Badiali S, Fargion S, Magni P, Valenti L, Dongiovanni P. Liver fat accumulation is associated with circulating PCSK9. Ann Med. 2016;48:384\u2013391.","journal-title":"Ann Med"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1097\/HJH.0b013e32834fa8b0","article-title":"Expert consensus document on the measurement of aortic stiffness in daily practice using carotid\u2010femoral pulse wave velocity","volume":"30","author":"Van Bortel LM","year":"2012","unstructured":"Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, DeBacker T, Filipovsky J, Huybrechts S, Mattace\u2010Raso FU, Protogerou AD,\u00a0Schillaci G, Segers P, Vermeersch S, Weber T; Artery Society; European\u00a0Society of Hypertension Working Group on Vascular Structure and Function; European Network for Noninvasive Investigation of Large Arteries . Expert consensus document on the measurement of aortic stiffness in daily practice using carotid\u2010femoral pulse wave velocity. J Hypertens. 2012;30:445\u2013448.","journal-title":"J Hypertens"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1159\/000051090","article-title":"Determination of aortic elastic modulus by pulse wave velocity and wall tracking in a rat model of aortic stiffness","volume":"38","author":"Marque V","year":"2001","unstructured":"Marque V, Van Essen H, Struijker\u2010Boudier HA, Atkinson J, Lartaud\u2010Idjouadiene I. Determination of aortic elastic modulus by pulse wave velocity and wall tracking in a rat model of aortic stiffness. J Vasc Res. 2001;38:546\u2013550.","journal-title":"J Vasc Res"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1253\/circj.70.1231","article-title":"Pulse wave analysis and pulse wave velocity: a review of blood pressure interpretation 100\u00a0years after Korotkov","volume":"70","author":"Hirata K","year":"2006","unstructured":"Hirata K, Kawakami M, O'Rourke MF. Pulse wave analysis and pulse wave velocity: a review of blood pressure interpretation 100\u00a0years after Korotkov. Circ J. 2006;70:1231\u20131239.","journal-title":"Circ J"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2147\/VHRM.S24877","article-title":"Central aortic blood pressure, augmentation index, and reflected wave transit time: reproducibility and repeatability of data obtained by oscillometry","volume":"7","author":"Ageenkova OA","year":"2011","unstructured":"Ageenkova OA, Purygina MA. Central aortic blood pressure, augmentation index, and reflected wave transit time: reproducibility and repeatability of data obtained by oscillometry. Vasc Health Risk Manag. 2011;7:649\u2013656.","journal-title":"Vasc Health Risk Manag"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/hr.2009.154","article-title":"Validity and repeatability of the Vicorder apparatus: a comparison with the SphygmoCor device","volume":"32","author":"Hickson SS","year":"2009","unstructured":"Hickson SS, Butlin M, Broad J, Avolio AP, Wilkinson IB, McEniery CM. Validity and repeatability of the Vicorder apparatus: a comparison with the SphygmoCor device. Hypertens Res. 2009;32:1079\u20131085.","journal-title":"Hypertens Res"},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1097\/HJH.0b013e32835a8eb1","article-title":"Evaluation of the Vicorder, a novel cuff\u2010based device for the noninvasive estimation of central blood pressure","volume":"31","author":"Pucci G","year":"2013","unstructured":"Pucci G, Cheriyan J, Hubsch A, Hickson SS, Gajendragadkar PR, Watson T, O'Sullivan M, Woodcock\u2010Smith J, Schillaci G, Wilkinson IB, McEniery CM. Evaluation of the Vicorder, a novel cuff\u2010based device for the noninvasive estimation of central blood pressure. J Hypertens. 2013;31:77\u201385.","journal-title":"J Hypertens"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.atherosclerosis.2010.09.027","article-title":"Serum PCSK9 is associated with multiple metabolic factors in a large Han Chinese population","volume":"213","author":"Cui Q","year":"2010","unstructured":"Cui Q, Ju X, Yang T, Zhang M, Tang W, Chen Q, Hu Y, Haas JV, Troutt JS, Pickard RT, Darling R, Konrad RJ, Zhou H, Cao G. Serum PCSK9 is associated with multiple metabolic factors in a large Han Chinese population. Atherosclerosis. 2010;213:632\u2013636.","journal-title":"Atherosclerosis"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1161\/ATVBAHA.110.214130","article-title":"Circulating proprotein convertase subtilisinkexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans","volume":"30","author":"Persson L","year":"2010","unstructured":"Persson L, Cao G, St\u00e5hle L, Sj\u00f6berg BG, Troutt JS, Konrad RJ, G\u00e4lman C, Wall\u00e9n H, Eriksson M, Hafstr\u00f6m I, Lind S, Dahlin M, Amark P, Angelin B, Rudling M. Circulating proprotein convertase subtilisinkexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans. Arterioscler Thromb Vasc Biol. 2010;30:2666\u20132672.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1194\/jlr.M008144","article-title":"High\u2010dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol","volume":"51","author":"Weider G","year":"2010","unstructured":"Weider G, Zineh I, Pacanowski MA, Troutt JS, Cao G, Konrad RJ. High\u2010dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol. J Lipid Res. 2010;51:2714\u20132721.","journal-title":"J Lipid Res"},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1161\/CIRCRESAHA.116.308811","article-title":"PCSK9 association with lipoprotein(a)","volume":"119","author":"Tavori H","year":"2016","unstructured":"Tavori H, Christian D, Minnier J, Plubell D, Shapiro MD, Yeang C, Giunzioni I, Croyal M, Duell PB, Lambert G, Tsimikas S, Fazio S. PCSK9 association with lipoprotein(a). Circ Res. 2016;119:29\u201335.","journal-title":"Circ Res"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1042\/CS20140832","article-title":"Circulating PCSK9 levels are positively correlated with NMR\u2010assessed atherogenic dyslipidaemia in patients with high cardiovascular risk","volume":"128","author":"Guardiola M","year":"2015","unstructured":"Guardiola M, Plana N, Ibarretxe D, Cabr\u00e9 A, Gonz\u00e1lez M, Ribalta J, Masana L. Circulating PCSK9 levels are positively correlated with NMR\u2010assessed atherogenic dyslipidaemia in patients with high cardiovascular risk. Clin Sci. 2015;128:877\u2013882.","journal-title":"Clin Sci"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/hr.2016.38","article-title":"Plasma PCSK9 level is unrelated to blood pressure and not associated independently with carotid intima\u2010media thickness in hypertensives","volume":"39","author":"Yang SH","year":"2016","unstructured":"Yang SH, Du Y, Li S, Zhang Y, Xu RX, Zhu CG, Guo YL, Wu NQ, Dong Q, Sun J, Li JJ. Plasma PCSK9 level is unrelated to blood pressure and not associated independently with carotid intima\u2010media thickness in hypertensives. Hypertens Res. 2016;39:598\u2013605.","journal-title":"Hypertens Res"},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.2147\/DDDT.S67498","article-title":"Profile of evolocumab and its potential in the treatment of hyperlipidemia","volume":"9","author":"Cicero AF","year":"2015","unstructured":"Cicero AF, Colletti A, Borghi C. Profile of evolocumab and its potential in the treatment of hyperlipidemia. Drug Des Devel Ther. 2015;9:3073\u20133082.","journal-title":"Drug Des Devel Ther"},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1001\/jama.2016.16951","article-title":"Effect of evolocumab on progression of coronary disease in statin\u2010treated patients: the GLAGOV randomized clinical trial","volume":"316","author":"Nicholls SJ","year":"2016","unstructured":"Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJ, Koenig W, Somaratne R, Kassahun H, Yang J, Wasserman SM, Scott R, Ungi I, Podolec J, Ophuis AO, Cornel JH, Borgman M, Brennan DM, Nissen SE. Effect of evolocumab on progression of coronary disease in statin\u2010treated patients: the GLAGOV randomized clinical trial. JAMA. 2016;316:2373\u20132384.","journal-title":"JAMA"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.atherosclerosis.2016.03.010","article-title":"PCSK9 in relation to coronary plaque inflammation: results of the ATHEROREMO\u2010IVUS study","volume":"248","author":"Cheng JM","year":"2016","unstructured":"Cheng JM, Oemrawsingh RM, Garcia\u2010Garcia HM, Boersma E, van Geuns RJ, Serruys PW, Kardys I, Akkerhuis KM. PCSK9 in relation to coronary plaque inflammation: results of the ATHEROREMO\u2010IVUS study. Atherosclerosis. 2016;248:117\u2013122.","journal-title":"Atherosclerosis"},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.vph.2014.03.004","article-title":"Risk prediction with proprotein convertase subtilisin\/kexin type 9 (PCSK9) in patients with stable coronary disease on statin treatment","volume":"62","author":"Werner C","year":"2014","unstructured":"Werner C, Hoffmann MM, Winkler K, Bohm M, Laufs U. Risk prediction with proprotein convertase subtilisin\/kexin type 9 (PCSK9) in patients with stable coronary disease on statin treatment. Vascul Pharmacol. 2014;62:94\u2013102.","journal-title":"Vascul Pharmacol"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1185\/03007995.2015.1087985","article-title":"The role of uric acid in the development of cardiovascular disease","volume":"31","author":"Borghi C","year":"2015","unstructured":"Borghi C. The role of uric acid in the development of cardiovascular disease. Curr Med Res Opin. 2015;31:1\u20132.","journal-title":"Curr Med Res Opin"},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.amjcard.2012.12.034","article-title":"Association of serum uric acid and cardiovascular disease in healthy adults","volume":"111","author":"Kivity S","year":"2013","unstructured":"Kivity S, Kopel E, Maor E, Abu\u2010Bachar F, Segev S, Sidi Y, Olchovsky D. Association of serum uric acid and cardiovascular disease in healthy adults. Am J Cardiol. 2013;111:1146\u20131151.","journal-title":"Am J Cardiol"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.atherosclerosis.2016.07.922","article-title":"Prediction of cardiovascular events with levels of proprotein convertase subtilisin\/kexin type 9: a systematic review and meta\u2010analysis","volume":"252","author":"Vlachopoulos C","year":"2016","unstructured":"Vlachopoulos C, Terentes\u2010Printzios D, Georgiopoulos G, Skoumas I, Koutagiar I, Ioakeimidis N, Stefanadis C, Tousoulis D. Prediction of cardiovascular events with levels of proprotein convertase subtilisin\/kexin type 9: a systematic review and meta\u2010analysis. Atherosclerosis. 2016;252:50\u201360.","journal-title":"Atherosclerosis"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1056\/NEJMoa1604304","article-title":"Variation in PCSK9 and HMGCR and risk of cardiovascular disease and diabetes","volume":"375","author":"Ference BA","year":"2016","unstructured":"Ference BA, Robinson JG, Brook RD, Catapano AL, Chapman MJ, Neff DR, Voros S, Giugliano RP, Davey Smith G, Fazio S, Sabatine MS. Variation in PCSK9 and HMGCR and risk of cardiovascular disease and diabetes. N Engl J Med. 2016;375:2144\u20132153.","journal-title":"N Engl J Med"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.117.005764","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T23:33:31Z","timestamp":1760484811000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.117.005764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5]]},"references-count":39,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1161\/JAHA.117.005764"],"URL":"https:\/\/doi.org\/10.1161\/jaha.117.005764","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5]]},"assertion":[{"value":"2017-02-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-05-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e005764"}}