Clinical trial NCT06606821: The Effects of Tirzepatide in People With Overweight/Obesity and Coronary Artery Disease
Official title: The Effects of Tirzepatide on Coronary Plaque Lipid Content and Myocardial Microvascular Function in Overweight and Obese People With Coronary Disease - The IDEAL-COR Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Coronary Artery Disease
Coronary Microvascular Dysfunction
Overweight or Obesity
Stable Angina Pectoris
Chronic Coronary Artery Disease
Atherosclerosis Cardiovascular Disease
Keywords: NIRS
IVUS
GLP-1
Tirzepatide
Intravascular imagining
Stable Angina Pectoris
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
First posted: 2024-09-23
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to investigate, as a proof-of-principle, long-term (52 weeks) effects of tirzepatide once-weekly vs. placebo on changes in coronary plaque composition and progression (assessed by NIRS), plaque burden (assessed by IVUS) and microvascular function (assessed by invasively measured CFR) in overweight and obese individuals with stable coronary artery disease (CAD). In addition, the objective of a baseline cross-sectional sub-study is to explore potential metabolic and cardiovascular (CV) predictors for high arteriosclerotic plaque burden in overweight and obese individuals and to establish a cohort for future research projects.

Detailed description: The anti-atherogenic effect of tirzepatide has been studied in preclinical studies and seems to involve mechanisms related to a reduction in vascular inflammation and lipid accumulation. Any direct anti-atherogenic effect of tirzepatide may potentially reduce the incidence of major cardiovascular endpoints in individuals with overweight or obesity. As a proof of principle, it would be of scientific and clinical interest to explore the anti-atherogenic effect of tirzepatide in humans. IVUS-NIRS imaging is uniquely suited for this purpose, as it makes it possible to detect changes in not only atheroma burden by IVUS but also to detect progression within the plaques in the lipidic/necrotic core component by NIRS. LCBItotal allows for consecutive detection of small changes in the same individual, which is pivotal to explore the supposed antiatherogenic mechanism of tirzepatide with enough statistical power.

The investigators hypothesize that once-weekly sc. tirzepatide can reduce coronary lipid accumulation in the arterial wall and the progression of atheromatosis in individuals with overweight or obesity and established high-risk atherosclerosis. The investigators aim to investigate this hypothesis in a proof-of-principle study by investigating the change in coronary plaque composition in individuals with overweight or obesity and coronary artery disease (CAD) with high-risk characteristics by NIRS imaging randomised to 52-week treatment with tirzepatide or placebo.

Eligibility criteria: Inclusion Criteria:

* Informed written consent
* BMI equal to or above 27 kg/m2
* Age 18 years or older
* Referred to coronary angiogram (CAG) due to stable angina
* Coronary atheromatosis by angiography (obstructive or non-obstructive)
* LCBI4mm \>200 by NIRS in a vessel not subjected to coronary intervention

Exclusion Criteria:

* History of diabetes or HbA1c ≥48 mmol/mol (6.5%) at baseline
* Treatment with Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA)
* History of coronary artery bypass surgery (CABG)
* Planned CV intervention (including percutaneous coronary intervention, cardiac surgery or transcatheter valve intervention) at time of randomisation
* History of heart failure New York Heart Association (NYHA) class III or IV
* Left ventricular ejection fraction (LVEF) ≤35%
* eGFR \<30 ml/min/1.53 m2
* History of pancreatitis or plasma amylase \>2 times upper normal limit
* Impaired hepatic function at baseline (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times the upper limit of normal)
* Pregnancy, planned pregnancy or breastfeeding
* Family or history of multiple endocrine neoplasia (MEN) type 2 or familial medullary thyroid carcinoma (FMTC)
* Hypersensitivity to the active substance (Tirzepatide) or to any of the excipients
* Left main stenosis (≥50% diameter or haemodynamically significant)
* Chronic total occlusion of any major coronary vessel
* Multi-vessel disease or complex anatomy potentially requiring coronary bypass surgery
* Coronary anatomy or pathology precluding the safe performance of intravascular imaging in all major coronary arteries not subjected to intervention

Primary outcomes:
measure: Lipid core burden index
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Secondary outcomes:
measure: Percent atheroma volume (PAV)
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Number of high-risk coronary lesion
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Coronary flow reserve
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Other outcomes:
measure: Plasma lipid profile
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Markers of inflammation
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Left ventricular systolic and diastolic function assessed by echocardiography:
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Body composition assessed by DXA scan:
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Urine markers of oxidative stress
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Myocardial work
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Seattle Angina Questionnaire-7
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Thromboelastography
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: EuroQoL 5-Dimension 5-Level
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Liver stiffness measurement
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Controlled Attenuation Parameter
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Homeostatic Model Assessment for Insulin Resistance
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Fibrosis-4 score
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Glycaemic profile
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Change in glycaemic variability
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Change in fasting plasma glucose
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Change in glycated haemoglobin A1c
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
measure: Index of microcirculatory resistance
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo
measure: Resistive Reserve Ratio
timeFrame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Gentofte
country: Denmark
facility: Gentofte Hospital
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Tina Vilsbøll, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4.
citation: Stoner MCD, Bhushan NL, Maragh-Bass AC, Mitchell JT, Riggins L, Walker M, LeMasters K, Reese B, Dearing A, Debnam S, Golin C, Lightfoot AF, Pettifor A. Using Participatory Methods to Assess PrEP Interest and Uptake Among Young People Living in the Southeastern US: A Mixed Methods Assessment. AIDS Behav. 2022 May;26(5):1672-1683. doi: 10.1007/s10461-021-03519-y. Epub 2021 Nov 1.
citation: Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3.
citation: Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C, Urva S, Gimeno RE, Milicevic Z, Robins D, Haupt A. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018 Nov 17;392(10160):2180-2193. doi: 10.1016/S0140-6736(18)32260-8. Epub 2018 Oct 4.
citation: Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25.
citation: Kristensen SL, Rorth R, Jhund PS, Docherty KF, Sattar N, Preiss D, Kober L, Petrie MC, McMurray JJV. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019 Oct;7(10):776-785. doi: 10.1016/S2213-8587(19)30249-9. Epub 2019 Aug 14.
citation: Caruso I, Cignarelli A, Giorgino F. Heterogeneity and Similarities in GLP-1 Receptor Agonist Cardiovascular Outcomes Trials. Trends Endocrinol Metab. 2019 Sep;30(9):578-589. doi: 10.1016/j.tem.2019.07.004. Epub 2019 Aug 7.
citation: ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 6. Glycemic Targets: Standards of Care in Diabetes-2023. Diabetes Care. 2023 Jan 1;46(Suppl 1):S97-S110. doi: 10.2337/dc23-S006.
citation: Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Ryden L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019 Jul 13;394(10193):121-130. doi: 10.1016/S0140-6736(19)31149-3. Epub 2019 Jun 9.
citation: Hernandez AF, Green JB, Janmohamed S, D'Agostino RB Sr, Granger CB, Jones NP, Leiter LA, Rosenberg AE, Sigmon KN, Somerville MC, Thorpe KM, McMurray JJV, Del Prato S; Harmony Outcomes committees and investigators. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018 Oct 27;392(10157):1519-1529. doi: 10.1016/S0140-6736(18)32261-X. Epub 2018 Oct 2.
citation: Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22. doi: 10.1056/NEJMoa1603827. Epub 2016 Jun 13.
citation: Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15.
citation: Oh J, Teoh H, Leiter LA. Should C-reactive protein be a target of therapy? Diabetes Care. 2011 May;34 Suppl 2(Suppl 2):S155-60. doi: 10.2337/dc11-s211. No abstract available.
citation: Howard G, Wagenknecht LE, Burke GL, Diez-Roux A, Evans GW, McGovern P, Nieto FJ, Tell GS. Cigarette smoking and progression of atherosclerosis: The Atherosclerosis Risk in Communities (ARIC) Study. JAMA. 1998 Jan 14;279(2):119-24. doi: 10.1001/jama.279.2.119.
citation: Mundi S, Massaro M, Scoditti E, Carluccio MA, van Hinsbergh VWM, Iruela-Arispe ML, De Caterina R. Endothelial permeability, LDL deposition, and cardiovascular risk factors-a review. Cardiovasc Res. 2018 Jan 1;114(1):35-52. doi: 10.1093/cvr/cvx226.
citation: Bai X, Yang X, Jia X, Rong Y, Chen L, Zeng T, Deng X, Li W, Wu G, Wang L, Li Y, Zhang J, Xiong Z, Xiong L, Wang Y, Zhu L, Zhao Y, Jin S. CAV1-CAVIN1-LC3B-mediated autophagy regulates high glucose-stimulated LDL transcytosis. Autophagy. 2020 Jun;16(6):1111-1129. doi: 10.1080/15548627.2019.1659613. Epub 2019 Sep 4.
citation: Langheim S, Dreas L, Veschini L, Maisano F, Foglieni C, Ferrarello S, Sinagra G, Zingone B, Alfieri O, Ferrero E, Maseri A, Ruotolo G. Increased expression and secretion of resistin in epicardial adipose tissue of patients with acute coronary syndrome. Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H746-53. doi: 10.1152/ajpheart.00617.2009. Epub 2010 Jan 8.
citation: Boren J, Chapman MJ, Krauss RM, Packard CJ, Bentzon JF, Binder CJ, Daemen MJ, Demer LL, Hegele RA, Nicholls SJ, Nordestgaard BG, Watts GF, Bruckert E, Fazio S, Ference BA, Graham I, Horton JD, Landmesser U, Laufs U, Masana L, Pasterkamp G, Raal FJ, Ray KK, Schunkert H, Taskinen MR, van de Sluis B, Wiklund O, Tokgozoglu L, Catapano AL, Ginsberg HN. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2020 Jun 21;41(24):2313-2330. doi: 10.1093/eurheartj/ehz962. No abstract available.
citation: Piche ME, Tchernof A, Despres JP. Obesity Phenotypes, Diabetes, and Cardiovascular Diseases. Circ Res. 2020 May 22;126(11):1477-1500. doi: 10.1161/CIRCRESAHA.120.316101. Epub 2020 May 21.
citation: Kim SH, Despres JP, Koh KK. Obesity and cardiovascular disease: friend or foe? Eur Heart J. 2016 Dec 21;37(48):3560-3568. doi: 10.1093/eurheartj/ehv509. Epub 2015 Dec 18.
citation: Hou J, Renigunta A, Konrad M, Gomes AS, Schneeberger EE, Paul DL, Waldegger S, Goodenough DA. Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex. J Clin Invest. 2008 Feb;118(2):619-28. doi: 10.1172/JCI33970.
citation: Nakamura K, Fuster JJ, Walsh K. Adipokines: a link between obesity and cardiovascular disease. J Cardiol. 2014 Apr;63(4):250-9. doi: 10.1016/j.jjcc.2013.11.006. Epub 2013 Dec 16.
citation: Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003 Dec;112(12):1796-808. doi: 10.1172/JCI19246.
citation: Kang SJ, Mintz GS, Pu J, Sum ST, Madden SP, Burke AP, Xu K, Goldstein JA, Stone GW, Muller JE, Virmani R, Maehara A. Combined IVUS and NIRS detection of fibroatheromas: histopathological validation in human coronary arteries. JACC Cardiovasc Imaging. 2015 Feb;8(2):184-94. doi: 10.1016/j.jcmg.2014.09.021. Epub 2015 Jan 7.
citation: Negi SI, Didier R, Ota H, Magalhaes MA, Popma CJ, Kollmer MR, Spad MA, Torguson R, Suddath W, Satler LF, Pichard A, Waksman R. Role of near-infrared spectroscopy in intravascular coronary imaging. Cardiovasc Revasc Med. 2015 Jul-Aug;16(5):299-305. doi: 10.1016/j.carrev.2015.06.001. Epub 2015 Jun 10.
citation: Chen S, Okahara F, Osaki N, Shimotoyodome A. Increased GIP signaling induces adipose inflammation via a HIF-1alpha-dependent pathway and impairs insulin sensitivity in mice. Am J Physiol Endocrinol Metab. 2015 Mar 1;308(5):E414-25. doi: 10.1152/ajpendo.00418.2014. Epub 2014 Dec 23.
citation: Otake H, Tanimura K, Sugizaki Y, Toba T, Kawamori H, Shinke T, Hirata KI. Effect of Alirocumab and Rosuvastatin or Rosuvastatin Alone on Lipid Core Plaque in Coronary Artery Disease Seen on Near-Infrared Spectroscopy Intravascular Ultrasound (ANTARES). Circ Rep. 2019 Jan 31;1(2):107-111. doi: 10.1253/circrep.CJ-18-0021.
citation: Honda S, Sidharta SL, Shishikura D, Takata K, Di Giovanni GA, Nguyen T, Janssan A, Kim SW, Andrews J, Psaltis PJ, Worthley MI, Nicholls SJ. High-density lipoprotein cholesterol associated with change in coronary plaque lipid burden assessed by near infrared spectroscopy. Atherosclerosis. 2017 Oct;265:110-116. doi: 10.1016/j.atherosclerosis.2017.08.016. Epub 2017 Aug 31.
citation: Kini AS, Vengrenyuk Y, Shameer K, Maehara A, Purushothaman M, Yoshimura T, Matsumura M, Aquino M, Haider N, Johnson KW, Readhead B, Kidd BA, Feig JE, Krishnan P, Sweeny J, Milind M, Moreno P, Mehran R, Kovacic JC, Baber U, Dudley JT, Narula J, Sharma S. Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study. J Am Coll Cardiol. 2017 Feb 14;69(6):628-640. doi: 10.1016/j.jacc.2016.10.029. Epub 2016 Oct 29.
citation: Kini AS, Baber U, Kovacic JC, Limaye A, Ali ZA, Sweeny J, Maehara A, Mehran R, Dangas G, Mintz GS, Fuster V, Narula J, Sharma SK, Moreno PR. Changes in plaque lipid content after short-term intensive versus standard statin therapy: the YELLOW trial (reduction in yellow plaque by aggressive lipid-lowering therapy). J Am Coll Cardiol. 2013 Jul 2;62(1):21-9. doi: 10.1016/j.jacc.2013.03.058. Epub 2013 May 1.
citation: Biccire FG, Budassi S, Ozaki Y, Boi A, Romagnoli E, Di Pietro R, Bourantas CV, Marco V, Paoletti G, Debelak C, Sammartini E, Versaci F, Fabbiocchi F, Burzotta F, Pastori D, Crea F, Arbustini E, Alfonso F, Prati F. Optical coherence tomography-derived lipid core burden index and clinical outcomes: results from the CLIMA registry. Eur Heart J Cardiovasc Imaging. 2023 Mar 21;24(4):437-445. doi: 10.1093/ehjci/jeac110.
citation: NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet. 2016 Apr 2;387(10026):1377-1396. doi: 10.1016/S0140-6736(16)30054-X.
citation: Adair T, Lopez AD. The role of overweight and obesity in adverse cardiovascular disease mortality trends: an analysis of multiple cause of death data from Australia and the USA. BMC Med. 2020 Aug 4;18(1):199. doi: 10.1186/s12916-020-01666-y.
citation: Patel D, Hamamdzic D, Llano R, Patel D, Cheng L, Fenning RS, Bannan K, Wilensky RL. Subsequent development of fibroatheromas with inflamed fibrous caps can be predicted by intracoronary near infrared spectroscopy. Arterioscler Thromb Vasc Biol. 2013 Feb;33(2):347-53. doi: 10.1161/ATVBAHA.112.300710. Epub 2013 Jan 3.
citation: Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000 May;20(5):1262-75. doi: 10.1161/01.atv.20.5.1262. No abstract available.
citation: Lopez AD, Adair T. Is the long-term decline in cardiovascular-disease mortality in high-income countries over? Evidence from national vital statistics. Int J Epidemiol. 2019 Dec 1;48(6):1815-1823. doi: 10.1093/ije/dyz143.
citation: Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, Barengo NC, Beaton AZ, Benjamin EJ, Benziger CP, Bonny A, Brauer M, Brodmann M, Cahill TJ, Carapetis J, Catapano AL, Chugh SS, Cooper LT, Coresh J, Criqui M, DeCleene N, Eagle KA, Emmons-Bell S, Feigin VL, Fernandez-Sola J, Fowkes G, Gakidou E, Grundy SM, He FJ, Howard G, Hu F, Inker L, Karthikeyan G, Kassebaum N, Koroshetz W, Lavie C, Lloyd-Jones D, Lu HS, Mirijello A, Temesgen AM, Mokdad A, Moran AE, Muntner P, Narula J, Neal B, Ntsekhe M, Moraes de Oliveira G, Otto C, Owolabi M, Pratt M, Rajagopalan S, Reitsma M, Ribeiro ALP, Rigotti N, Rodgers A, Sable C, Shakil S, Sliwa-Hahnle K, Stark B, Sundstrom J, Timpel P, Tleyjeh IM, Valgimigli M, Vos T, Whelton PK, Yacoub M, Zuhlke L, Murray C, Fuster V; GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing Group. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. J Am Coll Cardiol. 2020 Dec 22;76(25):2982-3021. doi: 10.1016/j.jacc.2020.11.010.
citation: Raber L, Taniwaki M, Zaugg S, Kelbaek H, Roffi M, Holmvang L, Noble S, Pedrazzini G, Moschovitis A, Luscher TF, Matter CM, Serruys PW, Juni P, Garcia-Garcia HM, Windecker S; IBIS 4 (Integrated Biomarkers and Imaging Study-4) Trial Investigators (NCT00962416). Effect of high-intensity statin therapy on atherosclerosis in non-infarct-related coronary arteries (IBIS-4): a serial intravascular ultrasonography study. Eur Heart J. 2015 Feb 21;36(8):490-500. doi: 10.1093/eurheartj/ehu373. Epub 2014 Sep 2.
citation: Weisbrod RM, Shiang T, Al Sayah L, Fry JL, Bajpai S, Reinhart-King CA, Lob HE, Santhanam L, Mitchell G, Cohen RA, Seta F. Arterial stiffening precedes systolic hypertension in diet-induced obesity. Hypertension. 2013 Dec;62(6):1105-10. doi: 10.1161/HYPERTENSIONAHA.113.01744. Epub 2013 Sep 23.