Original Article| Volume 12, ISSUE 2, P356-366, March 2018

Visit-to-visit variability of lipid measurements as predictors of cardiovascular events

Published:December 20, 2017DOI:


      • Visit-to-visit variability in high-density lipoprotein cholesterol, triglycerides, and low-density lipoprotein-cholesterol are predictive of coronary events.
      • Visit-to-visit variability in triglycerides and low-density lipoprotein cholesterol are predictive of incident diabetes.
      • The correlation among the variability of the 3 lipid measurements is weak.
      • The mechanisms accounting for these associations are unknown.


      Higher visit-to-visit variability in risk factors such as blood pressure and low-density lipoprotein (LDL)-cholesterol are associated with an increase in cardiovascular (CV) events.


      The purpose of this study was to determine whether variability in high-density lipoprotein cholesterol (HDL-C) and triglyceride levels predicted coronary and CV events in a clinical trial population with known coronary disease.


      We assessed intraindividual variability in fasting high-density lipoprotein (HDL)-cholesterol, triglyceride, and LDL-cholesterol measurements among 9572 patients in the Treating to New Targets trial and correlated the results with coronary events over a median follow-up of 4.9 years.


      In the fully adjusted Cox model, 1 standard deviation of average successive variability, defined as the average absolute difference between successive values, was associated with an increased risk of a coronary event for HDL-cholesterol (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.11–1.21, P < .0001), for triglycerides (HR 1.09, 95% CI 1.04–1.15, P = .0005), and for LDL-cholesterol (HR 1.14, 95% CI 1.09–1.19, P < .0001). Similar results were found for the 3 other measures of variability, standard deviation, coefficient of variability, and variability independent of the mean. Similar results were seen for CV events, stroke, and nonfatal myocardial infarction. Higher variability in triglyceride and LDL-cholesterol, but not HDL-cholesterol, was predictive of incident diabetes. The correlation among the variability of the 3 lipid measurements was weak.


      Visit-to-visit variability in fasting measurements of HDL-cholesterol, triglycerides, and LDL-cholesterol are predictive of coronary events, CV events, and for triglyceride and low-density lipoprotein cholesterol variability, incident diabetes. The mechanisms accounting for these associations remain to be determined.

      Graphical abstract


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        • Rothwell P.M.
        • Howard S.C.
        • Dolan E.
        • et al.
        Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.
        Lancet. 2010; 375: 895-905
        • Stevens S.L.
        • Wood S.
        • Koshiaris C.
        • et al.
        Blood pressure variability and cardiovascular disease: systematic review and meta-analysis.
        BMJ. 2016; 354: i4098
        • Kreger B.E.
        • Odell P.M.
        • D'Agostino R.B.
        • Wilson P.F.
        Long-term intra-individual cholesterol variability: natural course and adverse impact on morbidity and mortality - the Framingham Study.
        Am Heart J. 1994; 127: 1607-1614
        • Bangalore S.
        • Breazna A.
        • DeMicco D.A.
        • Wun C.C.
        • Messerli F.H.
        Visit-to-visit low-density lipoprotein cholesterol variability and risk of cardiovascular outcomes: insights from the TNT trial.
        J Am Coll Cardiol. 2015; 65: 1539-1548
        • Bangalore S.
        • Fayyad R.
        • Messerli F.H.
        • et al.
        Relation of variability of low-density lipoprotein cholesterol and blood pressure to events in patients with previous myocardial infarction from the IDEAL trial.
        Am J Cardiol. 2017; 119: 379-387
        • Wilson P.W.
        • D’Agostino R.B.
        • Sullivan L.
        • Parise H.
        • Kannel W.B.
        Overweight and obesity as determinants of cardiovascular risk: the Framingham experience.
        Arch Intern Med. 2002; 162: 1867-1872
        • Bangalore S.
        • Fayyad R.
        • Laskey R.
        • DeMicco D.A.
        • Messerli F.H.
        • Waters D.D.
        Body-weight fluctuations and outcomes in coronary disease.
        N Engl J Med. 2017; 376: 1332-1340
        • Waters D.D.
        • Guyton J.R.
        • Herrington D.M.
        • McGowan M.P.
        • Wenger N.K.
        • Shear C.
        Treating to New Targets (TNT) Study: does lowering low-density lipoprotein cholesterol levels below currently recommended guidelines yield incremental clinical benefit?.
        Am J Cardiol. 2004; 93: 154-158
        • LaRosa J.C.
        • Grundy S.M.
        • Waters D.D.
        • et al.
        • for the Treating to New Targets (TNT) investigators
        Intensive lipid lowering with atorvastatin in patients with stable coronary disease.
        N Engl J Med. 2005; 352: 1425-1435
        • Nielsen S.F.
        • Nordestgaard B.G.
        Negative statin-related news stories decrease statin persistence an increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study.
        Eur Heart J. 2016; 37: 908-916
        • Bansal S.
        • Buring J.E.
        • Rifai N.
        • Mora S.
        • Sacks F.M.
        • Ridker P.M.
        Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women.
        JAMA. 2007; 298: 309-316
        • Nordestgaard B.G.
        • Benn M.
        • Schnohr P.
        • Tybjaerg-Hansen A.
        Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women.
        JAMA. 2007; 298: 299-308
        • Borén J.
        • Matikainen N.
        • Adiels M.
        • Taskinen M.R.
        Postprandial hypertriglyceridemia as a coronary risk factor.
        Clin Chim Acta. 2014; 431: 131-142
        • Nakamura K.
        • Miyoshi T.
        • Yunoki K.
        • Ito H.
        Postprandial hyperlipidemia as a potential residual risk factor.
        J Cardiol. 2016; 67: 335-339
        • Waters D.D.
        • Ho J.E.
        • DeMicco D.A.
        • et al.
        Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials.
        J Am Coll Cardiol. 2011; 57: 1535-1545
        • Mogadem M.
        • Ahmed S.W.
        • Mensch A.A.
        • Godwin I.D.
        Within person fluctuations of serum cholesterol and lipoproteins.
        Arch Intern Med. 1990; 150: 1645-1648
        • Bookstein L.
        • Gidding S.S.
        • Donovan M.
        • Smith F.A.
        Day-to-day variability of serum cholesterol, triglyceride and high density lipoprotein cholesterol levels.
        Arch Intern Med. 1990; 150: 1653-1657
        • Kafonek S.D.
        • Derby C.A.
        • Bachorik P.S.
        Biologic variability of lipoproteins and apolipoproteins in patients referred to a lipid clinic.
        Clin Chem. 1992; 38: 864-872
        • Boey E.
        • Gay G.M.
        • Poh K.K.
        • Yeo T.C.
        • Tan H.C.
        • Lee C.H.
        Visit-to-visit variability in LDL- and HDL-cholesterol is associated with adverse events after ST-segment elevation myocardial infarction: a 5-year follow-up study.
        Atherosclerosis. 2016; 244: 86-92
        • Smit R.A.
        • Trompet S.
        • Sabayan B.
        • et al.
        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.
        Circulation. 2016; 134: 212-221