Higher Visit-to-Visit Low-Density Lipoprotein Cholesterol Variability Is Associated With Lower Cognitive Performance, Lower Cerebral Blood Flow, and Greater White Matter Hyperintensity Load in Older Subjects.

Abstract:

BACKGROUND:Recently, it was shown that intraindividual variation in low-density lipoprotein cholesterol (LDL-C) predicts both cerebrovascular and cardiovascular events. We aimed to examine whether this extends to cognitive function and examined possible pathways using a magnetic resonance imaging substudy. METHODS:We investigated the association between LDL-C variability and 4 cognitive domains at month 30 in 4428 participants of PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). Additionally, we assessed the association of LDL-C variability with neuroimaging outcomes in a subset of 535 participants. LDL-C variability was defined as the intraindividual standard deviation over 4 postbaseline LDL-C measurements, and all analyses were adjusted for mean LDL-C levels and cardiovascular risk factors. RESULTS:Higher LDL-C variability was associated with lower cognitive function in both the placebo and pravastatin treatment arms. Associations were present for selective attention (P=0.017 and P=0.11, respectively), processing speed (P=0.20 and P=0.029), and memory (immediate recall, P=0.002 and P=0.006; delayed recall, P=0.001 and P≤0.001). Furthermore, higher LDL-C variability was associated with lower cerebral blood flow in both trial arms (P=0.031 and P=0.050) and with greater white matter hyperintensity load in the pravastatin arm (P=0.046). No evidence was found for interaction between LDL-C variability and pravastatin treatment for both cognitive and magnetic resonance imaging outcomes. CONCLUSIONS:We found that higher visit-to-visit variability in LDL-C, independently of mean LDL-C levels and statin treatment, is associated with lower cognitive performance, lower cerebral blood flow, and greater white matter hyperintensity load.

journal_name

Circulation

journal_title

Circulation

authors

Smit RA,Trompet S,Sabayan B,le Cessie S,van der Grond J,van Buchem MA,de Craen AJ,Jukema JW

doi

10.1161/CIRCULATIONAHA.115.020627

subject

Has Abstract

pub_date

2016-07-19 00:00:00

pages

212-21

issue

3

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.115.020627

journal_volume

134

pub_type

杂志文章,多中心研究,随机对照试验
  • The relationship of cardiac output and arterial pressure control.

    abstract::Many basic concepts of cardiac output and arterial pressure control have changed considerably in the past few years. In general, each tissue controls its own local resistance and blood flow regardless of the level of arterial pressure; the sum of the local flows then determines the venous return and cardiac output. Ho...

    journal_title:Circulation

    pub_type: 杂志文章,评审

    doi:10.1161/01.cir.64.6.1079

    authors: Guyton AC

    更新日期:1981-12-01 00:00:00

  • Effect of clopidogrel premedication in off-pump cardiac surgery: are we forfeiting the benefits of reduced hemorrhagic sequelae?

    abstract:BACKGROUND:Premedication with clopidogrel has reduced thrombotic complications after percutaneous coronary revascularization procedures. However, because of the enhanced and irreversible platelet inhibition by clopidogrel, patients requiring surgical revascularization have a higher risk of bleeding complications and tr...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.105.571828

    authors: Kapetanakis EI,Medlam DA,Petro KR,Haile E,Hill PC,Dullum MK,Bafi AS,Boyce SW,Corso PJ

    更新日期:2006-04-04 00:00:00

  • Time-varying myocardial stress and systolic pressure-stress relationship: role in myocardial-arterial coupling in hypertension.

    abstract:BACKGROUND:Myocardial afterload depends on left ventricular (LV) cavity size, pressure, and wall thickness, all of which change markedly throughout ejection. We assessed the relationship between instantaneous ejection-phase pressure and myocardial stress and the effect of arterial wave reflections on myocardial stress ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.108.829366

    authors: Chirinos JA,Segers P,Gupta AK,Swillens A,Rietzschel ER,De Buyzere ML,Kirkpatrick JN,Gillebert TC,Wang Y,Keane MG,Townsend R,Ferrari VA,Wiegers SE,St John Sutton M

    更新日期:2009-06-02 00:00:00

  • Relationship between intravascular ultrasound guidance and clinical outcomes after drug-eluting stents: the assessment of dual antiplatelet therapy with drug-eluting stents (ADAPT-DES) study.

    abstract:BACKGROUND:Prior small to modest-sized studies suggest a benefit of intravascular ultrasound (IVUS) guidance in noncomplex lesions. Whether IVUS guidance is associated with improved clinical outcomes after drug-eluting stent (DES) implantation in an unrestricted patient population is unknown. METHODS AND RESULTS:Asses...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1161/CIRCULATIONAHA.113.003942

    authors: Witzenbichler B,Maehara A,Weisz G,Neumann FJ,Rinaldi MJ,Metzger DC,Henry TD,Cox DA,Duffy PL,Brodie BR,Stuckey TD,Mazzaferri EL Jr,Xu K,Parise H,Mehran R,Mintz GS,Stone GW

    更新日期:2014-01-28 00:00:00

  • Abnormal blood pathways in left ventricular cavity in acute myocardial infarction. Experimental observations with special reference to regional wall motion abnormality and hemostasis.

    abstract::To elucidate the mechanism of regional hemostasis in the left ventricular (LV) cavity during myocardial infarction, the blood pathway in LV cavity was examined with contrast echocardiography injected from the left atrium before and after coronary ligation in nine canines. Before coronary ligation, contrast echoes spre...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.78.1.157

    authors: Beppu S,Izumi S,Miyatake K,Nagata S,Park YD,Sakakibara H,Nimura Y

    更新日期:1988-07-01 00:00:00

  • Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease. Implications for patient selection. Multivessel Angioplasty Prognosis Study Group.

    abstract::To assess the likelihood of procedural success in patients with multivessel coronary disease undergoing percutaneous coronary angioplasty, 350 consecutive patients (1,100 stenoses) from four clinical sites were evaluated. Eighteen variables characterizing the severity and morphology of each stenosis and 18 patient-rel...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.82.4.1193

    authors: Ellis SG,Vandormael MG,Cowley MJ,DiSciascio G,Deligonul U,Topol EJ,Bulle TM

    更新日期:1990-10-01 00:00:00

  • Effects of dietary omega 3 fatty acids on vascular contractility in preanoxic and postanoxic aortic rings.

    abstract:BACKGROUND:Vasomotor reactivity may contribute to the pathophysiology of ischemic injury. The atherosclerotic vessel may be particularly susceptible to vasoconstriction because of the damaged endothelial layer with resultant loss of vasodilatory factors. While dietary omega 3 fatty acids have been proposed to protect a...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.84.3.1393

    authors: Malis CD,Leaf A,Varadarajan GS,Newell JB,Weber PC,Force T,Bonventre JV

    更新日期:1991-09-01 00:00:00

  • The St. Jude valve. Thrombolysis as the first line of therapy for cardiac valve thrombosis.

    abstract:BACKGROUND:Thrombolytic therapy is a promising alternative to valve replacement in the management of prosthetic valve thrombosis. We sought to determine the short- and long-term results of treating thrombosed St. Jude heart valves with thrombolytic therapy as the primary treatment modality. METHODS AND RESULTS:Between...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.87.1.30

    authors: Silber H,Khan SS,Matloff JM,Chaux A,DeRobertis M,Gray R

    更新日期:1993-01-01 00:00:00

  • Exercise-induced myocardial ischemia in a cold environment. Effect of antianginal medications.

    abstract::The influence of cold on the threshold for myocardial ischemia and the efficacy of antianginal drugs in a cold environment were assessed in 24 patients with stable angina and exercise-induced ST depression. Treadmill exercise tests were done according to a randomized double-blind protocol 90 minutes after administrati...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1161/01.cir.79.5.1015

    authors: Juneau M,Johnstone M,Dempsey E,Waters DD

    更新日期:1989-05-01 00:00:00

  • Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity.

    abstract:BACKGROUND:The specific role of apoptosis in human atherosclerosis remains unknown. During apoptotic cell death, phosphatidylserine exposure on the cell surface confers a high tissue-factor (TF)-dependent procoagulant activity. METHODS AND RESULTS:In this study, we examined the role of apoptotic cell death in the prom...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.99.3.348

    authors: Mallat Z,Hugel B,Ohan J,Lesèche G,Freyssinet JM,Tedgui A

    更新日期:1999-01-26 00:00:00

  • Role of ATP-sensitive K+ channel on ECG ST segment elevation during a bout of myocardial ischemia. A study on epicardial mapping in dogs.

    abstract:BACKGROUND:ATP-sensitive K+ channels are activated when the myocardium becomes ischemic. However, the role of the ATP-sensitive K+ current in the emergence of ECG ST changes during ischemia remained unclarified. METHODS AND RESULTS:The left anterior descending coronary artery (LAD) was cannulated and perfused with art...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.88.4.1845

    authors: Kubota I,Yamaki M,Shibata T,Ikeno E,Hosoya Y,Tomoike H

    更新日期:1993-10-01 00:00:00

  • Impact of angiographic complete revascularization after drug-eluting stent implantation or coronary artery bypass graft surgery for multivessel coronary artery disease.

    abstract:BACKGROUND:This study sought to evaluate the clinical impact of angiographic complete revascularization (CR) after drug-eluting stent implantation or coronary artery bypass graft surgery for multivessel coronary disease. METHODS AND RESULTS:A total of 1914 consecutive patients with multivessel coronary disease undergo...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.110.005041

    authors: Kim YH,Park DW,Lee JY,Kim WJ,Yun SC,Ahn JM,Song HG,Oh JH,Park JS,Kang SJ,Lee SW,Lee CW,Park SW,Park SJ

    更新日期:2011-05-31 00:00:00

  • Extent of clinical improvement after surgical treatment of hypertrophic obstructive cardiomyopathy.

    abstract:BACKGROUND:A subgroup of patients with hypertrophic obstructive cardiomyopathy remain severely symptomatic despite optimal medical therapy. Septal myectomy reduces or eliminates left ventricular outflow obstruction and produces marked symptomatic improvement. With the recent advent of alternative methods for treatment ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.94.3.467

    authors: McCully RB,Nishimura RA,Tajik AJ,Schaff HV,Danielson GK

    更新日期:1996-08-01 00:00:00

  • Impact of controlled pericardial drainage on critical cardiac tamponade with acute type A aortic dissection.

    abstract:BACKGROUND:Cardiac tamponade is associated with fatal outcomes for patients with acute type A aortic dissection, and the presence of cardiac tamponade should prompt urgent aortic repair. However, treatment of the patient with critical cardiac tamponade who cannot survive until surgery remains unclear. We analyzed our e...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1161/CIRCULATIONAHA.111.082685

    authors: Hayashi T,Tsukube T,Yamashita T,Haraguchi T,Matsukawa R,Kozawa S,Ogawa K,Okita Y

    更新日期:2012-09-11 00:00:00

  • Extensive primary repair of the thoracic aorta in acute type a aortic dissection by means of ascending aorta replacement combined with open placement of triple-branched stent graft: early results.

    abstract:BACKGROUND:To simplify extensive primary repair of the thoracic aorta in acute type A aortic dissection, we developed the open triple-branched stent graft placement technique. The early results of this new technique are reported. METHODS AND RESULTS:Between June 2008 and November 2009, 30 patients with acute Stanford ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.110.946012

    authors: Chen LW,Dai XF,Lu L,Zhang GC,Cao H

    更新日期:2010-10-05 00:00:00

  • Myosin light chain phosphorylation is critical for adaptation to cardiac stress.

    abstract:BACKGROUND:Cardiac hypertrophy is a common response to circulatory or neurohumoral stressors as a mechanism to augment contractility. When the heart is under sustained stress, the hypertrophic response can evolve into decompensated heart failure, although the mechanism(s) underlying this transition remain largely unkno...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.112.116202

    authors: Warren SA,Briggs LE,Zeng H,Chuang J,Chang EI,Terada R,Li M,Swanson MS,Lecker SH,Willis MS,Spinale FG,Maupin-Furlowe J,McMullen JR,Moss RL,Kasahara H

    更新日期:2012-11-27 00:00:00

  • Supravalvular pulmonary stenosis after anatomic correction of transposition of the great arteries: causes and prevention.

    abstract::Twenty-two patients who underwent anatomic correction of transposition of the great arteries at the arterial level at the age of 8 weeks to 14 years were reinvestigated 1-4.6 years (mean 2.0 years) after operation. A Dacron tube was used to bridge the gap between the proximal pulmonary route and the distal pulmonary a...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:

    authors: Yacoub MH,Bernhard A,Radley-Smith R,Lange P,Sievers H,Heintzen P

    更新日期:1982-08-01 00:00:00

  • Correlation of myocardial ultrastructure and function.

    abstract::The electron microscopic structure of heart muscle and the ultrastructural basis of cardiac contraction have been reviewed. The relation between muscle length and developed tension has been explained in terms of the structure of the sarcomere, which is the basic unit of contraction. Using the derived length-tension cu...

    journal_title:Circulation

    pub_type: 杂志文章,评审

    doi:10.1161/01.cir.38.1.29

    authors: Sonnenblick EH

    更新日期:1968-07-01 00:00:00

  • Cross-sectional echocardiographic detection of aortic obstruction. 2. Coarctation of the Aorta.

    abstract::Cross-sectional echocardiographic studies of the aortic arch and proximal descending aorta were performed in 18 patients with coarctation of the aorta and 20 normal subjects. In normals the aortic arch and proximal descending aorta appeared as an arcuate, echo-free structure curving across the plane of the scan. There...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.57.3.498

    authors: Weyman AE,Caldwell RL,Hurwitz RA,Girod DA,Dillon JC,Feigenbaum H,Green D

    更新日期:1978-03-01 00:00:00

  • Evidence implicating nonmuscle myosin in restenosis. Use of in situ hybridization to analyze human vascular lesions obtained by directional atherectomy.

    abstract:BACKGROUND:Identification of genes that are specifically activated in restenosis lesions after percutaneous transluminal angioplasty represents a necessary step toward molecular manipulation designed to inhibit cellular proliferation responsible for such lesions. Whereas quiescent smooth muscle cells (contractile pheno...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.85.2.543

    authors: Leclerc G,Isner JM,Kearney M,Simons M,Safian RD,Baim DS,Weir L

    更新日期:1992-02-01 00:00:00

  • Effect of difficulty affording health care on health status after coronary revascularization.

    abstract:BACKGROUND:An objective of the United States' Healthy People 2010 Initiative is to eliminate disparities based on socioeconomic status. We assessed the effect of difficulty affording health care on the health status (symptoms, function, and quality of life) of patients treated with percutaneous coronary intervention or...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.104.474775

    authors: Spertus J,Decker C,Woodman C,House J,Jones P,O'Keefe J,Borkon AM

    更新日期:2005-05-24 00:00:00

  • Protective function of transcription factor TR3 orphan receptor in atherogenesis: decreased lesion formation in carotid artery ligation model in TR3 transgenic mice.

    abstract:BACKGROUND:Smooth muscle cells (SMCs) play a key role in intimal thickening in atherosclerosis and restenosis. The precise signaling pathways by which the proliferation of SMCs is regulated are largely unknown. The TR3 orphan receptor, the mitogen-induced nuclear orphan receptor (MINOR), and the nuclear receptor of T c...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.0000028811.03056.bf

    authors: Arkenbout EK,de Waard V,van Bragt M,van Achterberg TA,Grimbergen JM,Pichon B,Pannekoek H,de Vries CJ

    更新日期:2002-09-17 00:00:00

  • Risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicating acute myocardial infarction. GUSTO-I (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) Trial Investigators.

    abstract:BACKGROUND:Ventricular septal defect (VSD) complicating acute myocardial infarction has been studied primarily in small, prethrombolytic-era trials. Our goal was to determine clinical predictors and angiographic and clinical outcomes of this complication in the thrombolytic era. METHODS AND RESULTS:We compared enrollm...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1161/01.cir.101.1.27

    authors: Crenshaw BS,Granger CB,Birnbaum Y,Pieper KS,Morris DC,Kleiman NS,Vahanian A,Califf RM,Topol EJ

    更新日期:2000-01-04 00:00:00

  • Enzymatically degraded, nonoxidized LDL induces human vascular smooth muscle cell activation, foam cell transformation, and proliferation.

    abstract:BACKGROUND:Enzymatic, nonoxidative modification transforms LDL to an atherogenic molecule (E-LDL) that activates complement and macrophages and is present in early atherosclerotic lesions. METHODS AND RESULTS:We report on the atherogenic effects of E-LDL on human vascular smooth muscle cells (SMC). E-LDL accumulated i...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.101.15.1799

    authors: Klouche M,Rose-John S,Schmiedt W,Bhakdi S

    更新日期:2000-04-18 00:00:00

  • Inducible nitric oxide synthase mediates delayed myocardial protection induced by activation of adenosine A(1) receptors: evidence from gene-knockout mice.

    abstract:BACKGROUND:The mechanism of delayed preconditioning induced by activation of adenosine A(1) receptors (A(1)ARs) is not fully understood. We determined the role of inducible nitric oxide synthase (iNOS) in mediating adenosine-induced late cardioprotection using pharmacological inhibitors and iNOS gene-knockout mice. ME...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.102.8.902

    authors: Zhao T,Xi L,Chelliah J,Levasseur JE,Kukreja RC

    更新日期:2000-08-22 00:00:00

  • Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability.

    abstract:BACKGROUND:Growth of atherosclerotic plaques is accompanied by neovascularization from vasa vasorum microvessels extending through the tunica media into the base of the plaque and by lumen-derived microvessels through the fibrous cap. Microvessels are associated with plaque hemorrhage and may play a role in plaque rupt...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.CIR.0000143233.87854.23

    authors: Moreno PR,Purushothaman KR,Fuster V,Echeverri D,Truszczynska H,Sharma SK,Badimon JJ,O'Connor WN

    更新日期:2004-10-05 00:00:00

  • Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone.

    abstract:BACKGROUND:Patients surviving ventricular fibrillation (VF) or sustained ventricular tachycardia (VT) are at a high risk of death due to a recurrence of arrhythmia. The implantable cardioverter defibrillator (ICD) terminates VT or VF, but it is not known whether this device prolongs life in these patients compared with...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1161/01.cir.101.11.1297

    authors: Connolly SJ,Gent M,Roberts RS,Dorian P,Roy D,Sheldon RS,Mitchell LB,Green MS,Klein GJ,O'Brien B

    更新日期:2000-03-21 00:00:00

  • Expression of NADH/NADPH oxidase p22phox in human coronary arteries.

    abstract:BACKGROUND:NADH/NADPH oxidase is an important source of superoxide in the vasculature. Recently, we found that polymorphism of the gene p22phox, a critical component of this oxidase, is associated with a risk of coronary artery disease. The aim of this study was to investigate the localization of p22phox in human coron...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.100.14.1494

    authors: Azumi H,Inoue N,Takeshita S,Rikitake Y,Kawashima S,Hayashi Y,Itoh H,Yokoyama M

    更新日期:1999-10-05 00:00:00

  • Impact of prolonged cyclooxygenase-2 inhibition on inflammatory markers and endothelial function in patients with ischemic heart disease and raised C-reactive protein: a randomized placebo-controlled study.

    abstract:BACKGROUND:The impact of cyclooxygenase (COX)-2 antagonist treatment on acute coronary risk is controversial. We investigated the effect of prolonged COX-2 inhibition on inflammatory profile and endothelial function in patients with ischemic heart disease and high serum C-reactive protein (CRP) values. METHODS AND RES...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1161/01.CIR.0000139338.12464.5F

    authors: Bogaty P,Brophy JM,Noel M,Boyer L,Simard S,Bertrand F,Dagenais GR

    更新日期:2004-08-24 00:00:00

  • Acute ischemic ventricular septal defect.

    abstract::Thirty-one published reports (366 patients) and 48 consecutive patients treated for postinfarction ventricular septal defect at four institutions in northern California were reviewed. Overall hospital mortality was 43% in the reviewed group and was not affected by age, concomitant myocardial revascularization, date of...

    journal_title:Circulation

    pub_type: 杂志文章,评审

    doi:

    authors: Hill JD,Stiles QR

    更新日期:1989-06-01 00:00:00