ORIGINAL CONTRIBUTION Fasting Compared With Nonfasting Triglycerides and Risk of Cardiovascular Events in Women Sandeep Bansal, MD Context The association of triglycerides with incident cardiovascular disease re- Julie E. Buring, ScD mains controversial. Although triglyceride levels are typically obtained in the fasting Nader Rifai, PhD state, postprandial hypertriglyceridemia may play an important role in atherosclerosis. Objective To determine the association of triglyceride levels (fasting vs nonfasting) Samia Mora, MD, MHS and risk of future cardiovascular events. Frank M. Sacks, MD Design, Setting, and Participants Prospective study of 26 509 initially healthy Paul M Ridker, MD, MPH US women (20 118 fasting and 6391 nonfasting) participating in the Women’s Health Study, enrolled between November 1992 and July 1995 and undergoing follow-up N CONTRAST TO TOTAL CHOLES- for a median of 11.4 years. Triglyceride levels were measured in blood samples ob- terol, low-density lipoprotein cho- tained at time of enrollment. lesterol (LDL-C), and high- Main Outcome Measure Hazard ratios for incident cardiovascular events (non- density lipoprotein cholesterol fatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, or car- I(HDL-C), which are well-established in- diovascular death). dependent risk factors for cardiovas- 1 Results At baseline, triglyceride levels in fasting as well as nonfasting women corre- cular disease, the importance of tri- lated with traditional cardiac risk factors and markers of insulin resistance. During a median glycerides remains controversial. In part follow-up of 11.4 years, 1001 participants experienced an incident cardiovascular event this controversy reflects the fact that, (including 276 nonfatal myocardial infarctions, 265 ischemic strokes, 628 coronary revas- due to the inverse correlation of tri- cularizations, and 163 cardiovascular deaths), for an overall rate of 3.46 cardiovascular glyceride levels with those of HDL-C, events per 1000 person-years of follow-up. After adjusting for age, blood pressure, smok- adjustment for HDL-C attenuates the ing, and use of hormone therapy, both fasting and nonfasting triglyceride levels pre- relationship between triglycerides and dicted cardiovascular events. Among fasting participants, further adjustment for levels of cardiovascular disease. A recent meta- total and high-density lipoprotein cholesterol and measures of insulin resistance weak- ened this association (fully adjusted hazard ratio [95% confidence interval] for increasing analysis suggested that the adjusted risk tertiles of triglyceride levels: 1 [reference], 1.21 [0.96-1.52], and 1.09 [0.85-1.41] [P=.90 ratio for coronary heart disease among for trend]). In contrast, nonfasting triglyceride levels maintained a strong independent individuals in the highest third of tri- relationship with cardiovascular events in fully adjusted models (hazard ratio [95% con- glyceride levels compared with those in fidence interval] for increasing tertiles of levels: 1 [reference], 1.44 [0.90-2.29], and 1.98 the lowest third decreases from ap- [1.21-3.25] [P=.006 for trend]). In secondary analyses stratified by time since partici- proximately 2.0 to 1.5 after account- pants’ last meal, triglyceride levels measured 2 to 4 hours postprandially had the stron- ing for HDL-C levels.2 gest association with cardiovascular events (fully adjusted hazard ratio [95% confidence Ͻ A second aspect of the controversy interval] for highest vs lowest tertiles of levels, 4.48 [1.98-10.15] [P .001 for trend]), and this association progressively decreased with longer periods of fasting. stems from the manner in which tri- glyceride levels are typically mea- Conclusions In this cohort of initially healthy women, nonfasting triglyceride levels sured. Current national guidelines rec- were associated with incident cardiovascular events, independent of traditional car- ommend that blood for lipid profiles be diac risk factors, levels of other lipids, and markers of insulin resistance; by contrast, fasting triglyceride levels showed little independent relationship. drawn after an 8- to 12-hour fast.1 Be- JAMA. 2007;298(3):309-316 www.jama.com cause plasma triglyceride levels can in- crease substantially postprandially, fast- Author Affiliations: Donald W. Reynolds Center for Department of Laboratory Medicine, Children’s ing levels ostensibly avoid the variability Cardiovascular Research (Drs Bansal, Mora, and Hospital (Dr Rifai); and Department of Nutrition, Ridker), Leducq Center for Molecular and Genetic Harvard School of Public Health (Dr Sacks), Boston, associated with meals and provide a Epidemiology (Drs Rifai, Mora, and Ridker), Center Massachusetts. for Cardiovascular Disease Prevention and Division Corresponding Author: Paul M Ridker, MD, MPH, of Preventive Medicine (Drs Bansal, Buring, Mora, Center for Cardiovascular Disease Prevention, Brigham See also pp 299 and 336. and Ridker), and Division of Cardiology (Drs Mora and Women’s Hospital, 900 Commonwealth Ave E, and Ridker), Brigham and Women’s Hospital; Boston, MA 02215 ([email protected]). ©2007 American Medical Association. All rights reserved. (Reprinted) JAMA, July 18, 2007—Vol 298, No. 3 309 Downloaded From: https://jamanetwork.com/ on 10/01/2021 FASTING VS NONFASTING TRIGLYCERIDES AND RISK OF CARDIOVASCULAR EVENTS IN WOMEN more stable estimate for risk assess- blood sample for analysis. Partici- at least 24 hours; computed tomogra- ment. However, postprandial lipids may pants whose last meal was 8 or more phy scans or magnetic resonance im- play an important role in the patho- hours prior to their blood draw com- ages were available for most events and genesis of cardiovascular disease be- prised the fasting cohort (n=20 118), were used to distinguish ischemic from cause postprandial triglyceride-rich and those who had eaten within 8 hours hemorrhagic strokes. Coronary revas- remnant lipoproteins can penetrate the of their blood draw comprised the non- cularization included percutaneous coro- endothelial cell layer and reside in the fasting cohort (n=6391); those with un- nary interventions and coronary artery subendothelial space, where they can known time since last meal (n=1430) bypass graft surgery. All events were ad- contribute to the formation of foam were excluded from the analysis. judicated by an end points committee. cells, a hallmark of early atherosclero- In participants with more than 1 cardio- sis.3-5 Elevated postprandial levels of tri- Laboratory Methods vascular event, only the first was used in glycerides, via higher peak concentra- Blood samples were collected at enroll- these analyses. Follow-up morbidity and tions or delayed clearance, also might ment in tubes containing EDTA and mortality data were available for 97.2% represent an abnormal response to an were shipped cold overnight to a core and 99.4%, respectively, of the Wom- oral fat load that reflects insulin resis- laboratory certified by the US Centers en’s Health Study participants. tance,6-8 a condition associated with a for Disease Control and Prevention and host of metabolic abnormalities that the National Heart, Lung, and Blood In- Statistical Analyses predispose an individual to cardiovas- stitute Lipid Standardization Pro- All analyses were performed sepa- cular disease.9,10 To clarify the impor- gram. There, samples were centri- rately for fasting and nonfasting par- tance of the prandial state when mea- fuged and the plasma was stored in ticipants. For the main analyses, tri- suring triglyceride levels, we evaluated liquid nitrogen until analysis. glyceride levels were categorized into the association of fasting and nonfast- Triglyceride levels were measured en- tertiles for consistency with a recent ing levels with incident cardiovascu- zymatically, with correction for endog- meta-analysis2 and for stability of effect lar events in a large prospective co- enous glycerol,14 using a Hitachi 917 estimates by maintaining adequate hort of initially healthy women, analyzer and reagents and calibrators numbers of events in reference groups. independent of traditional cardiac risk from Roche Diagnostics (Indianapo- Because distributions differed be- factors, levels of other lipids, and mark- lis, Indiana). Triglycerides at concen- tween fasting and nonfasting partici- ers of insulin resistance. trations of 84.0 and 201.8 mg/dL (to pants, separate tertile cut points were convert to millimoles per liter, multi- defined for each cohort. To address METHODS ply by 0.0113) were determined in the whether our results might differ on the Study Participants laboratory with a day-to-day reproduc- basis of cut points used, secondary The study cohort was derived from par- ibility of 1.8% (SD, 1.6 mg/dL) and 1.7% analyses were performed dividing the ticipants in the Women’s Health Study, (SD, 3.5 mg/dL), respectively. Levels of study population into quintiles and a previously completed randomized total cholesterol and HDL-C were mea- treating triglyceride levels as a natural controlled trial of aspirin and vitamin sured enzymatically on a Hitachi 911 logarithm–transformed continuous E in the primary prevention of cardio- autoanalyzer (Roche Diagnostics, Basel, variable. vascular disease and cancer in women Switzerland), and levels of LDL-C were Differences between baseline char- aged 45 years and older. Details of the determined directly (Genzyme, Cam- acteristics of participants within each study design and primary outcomes bridge, Massachusetts). These assays are triglyceride