Association between triglycerides and cardiovascular events in primary populations: a meta-regression analysis and synthesis of evidence

Figures & data

Figure 1 Regression of triglycerides on the log of the rate ratio for (A) all trials, (B) primary prevention trials, and (C) secondary prevention trials. Each panel shows the output from regression analysis in Comprehensive Meta-Analysis.

Notes: (A) 40 trials, slope =0.488, P=0.005; (B) 11 trials, slope =1.031, P=0.010; (C) 25 trials, slope =0.373, P=0.114.

Table 1 Statistics for the regression analyses of lipid values versus cardiovascular eventsa

	Triglycerides		HDL-C		Total cholesterolb		LDL-C
	Slope	P-value	Slope	P-value	Slope	P-value	Slope	P-value
All studies (N=40)	0.488	0.005	0.085	0.822	1.030	<0.001	0.624	<0.001
Population (N=36)c
Primary prevention (N=11)	1.031	0.010	2.251	0.223	1.232	0.044	0.932	0.002
Secondary prevention (N=25)	0.373	0.114	−0.288	0.487	1.264	<0.001	0.507	<0.001
HDL-C level (N=40)
Low (N=20)	0.605	0.013	0.127	0.773	1.294	<0.001	0.539	<0.001
High (N=20)	0.624	0.018	0.719	0.367	0.602	0.041	0.776	<0.001
LDL-C level (N=40)
Low (N=20)	0.765	0.010	0.252	0.625	0.952	<0.001	0.585	<0.001
High (N=20)	0.352	0.136	−0.460	0.497	1.392	<0.001	0.888	<0.001
Total cholesterol level (n=38)b
Low (N=19)	0.765	0.005	−1.575	0.023	0.844	<0.001	0.594	<0.001
High (N=19)	0.456	0.107	−0.455	0.502	1.475	<0.001	1.026	<0.001

Notes:

a Bold font indicates statistical significance at P<0.05

b JUPITER and AIM-HIGH, which did not report total cholesterol, were omitted from analyses of total cholesterol

c the analyses omitted the four trials with mixed primary and secondary populations.

Abbreviations: AIM-HIGH, Atherothrombosis Intervention in Metabolic syndrome with low HDL/High triglycerides: Impact on Global Health outcomes; HDL-C, high-density lipoprotein cholesterol; JUPITER, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; LDL-C, low-density lipoprotein cholesterol.

Table S1 Clinical trials included in the analysis

Study acronym	Cardiovascular outcome	Timepoint (years)a	Treatment arm	N subjects	N events
Primary preventionb
AFCAPS/TexCAPS^Citation28	Fatal/non-fatal MI, unstable angina, cardiac death	1	Placebo	3,301	183
			Lovastatin	3,304	116
ALLHAT-LLT^Citation18	Coronary death or MI	2	Usual care	5,185	421
			Pravastatin	5,170	380
ASCOT-LLA^Citation29	Coronary death or MI	2	Placebo	5,137	154
			Atorvastatin	5,168	100
ENHANCE^Citation20	Coronary death, MI, stroke, revascularization	2	Simvastatin	363	7
			Simvastatin/ezetimibe	357	10
HHS^Citation30	Coronary death or MI	3	Placebo	2,035	84
			Gemfibrozil	2,046	56
JUPITER^Citation31	CV death, MI, stroke, angina, revascularization	4	Placebo	8,901	251
			Rosuvastatin	8,901	142
LRC-CPPT^Citation9	Coronary death or MI	7.4	Placebo	1,900	187
			Cholestyramine	1,906	155
MEGA^Citation33	Coronary death, MI, angina, revascularization	5.3-year mean	Diet	3,966	101
			Diet/pravastatin	3,866	66
METEOR^Citation32	MI, angina, coronary syndromes	2-year mean	Placebo	252	0
			Rosuvastatin	624	6
SPARCL^Citation19	Coronary death or MI	5-year mean	Placebo	2,366	121
			Atorvastatin	2,365	83
WOSCOPS^Citation34	Coronary death or MI	5	Placebo	3,293	248
			Pravastatin	3,302	174
Secondary preventionc
4S^Citation35	Coronary death or MI	5.4	Placebo	2,223	622
			Simvastatin	2,221	431
AFREGS^Citation36	Coronary death or hospitalization for angina	0.96	Placebo	72	16
			Niacin/gemfibrozil/cholestyramine	71	7
AIM-HIGH^Citation37	Coronary death, MI, revascularization	3.0	Placebo/simvastatin	1,696	274
			Niacin/simvastatin	1,718	282
ALLIANCE^Citation38	Coronary death, MI, angina, revascularization	4.6	Usual care	1,225	333
			Atorvastatin	1,217	289
A-Z^Citation39	Cardiovascular death, MI, readmission ACS, stroke	0.67	Placebo/simvastatin 20 mg	2,232	343
			Simvastatin 40/80 mg	2,265	309
BECAIT^Citation40	Coronary death or MI	5	Placebo	39	3
			Bezafibrate	42	3
BIP^Citation41	Fatal/non-fatal MI or sudden death	6.2	Placebo	1,542	232
			Bezafibrate	1,548	211
CARDS^Citation21	Fatal/non-fatal MI	2	Placebo	1,410	61
			Atorvastatin	1,428	33
CARE^Citation42	Coronary death or MI	5-year mean	Placebo	2,078	274
			Pravastatin	2,081	212
FIELD^Citation22	Coronary death or MI	5	Placebo	4,900	288
			Fenofibrate	4,895	256
GISSI-P^Citation43	Coronary death or MI	2-year median	Usual care	2,133	83
			Pravastatin	2,138	67
GREACE^Citation44	Coronary death, MI, angina, revascularization	3-year mean	Usual care	800	196
			Atorvastatin	800	96
HATS^Citation45	Coronary death or MI	3.0	Placebo	38	9
			Simvastatin/niacin	38	1
HERS^Citation46	Coronary death or MI	1	Placebo	1,383	176
			Estrogen-progestin	1,380	172
HHS ancillary^Citation47	Coronary death or MI	5-year mean	Placebo	317	24
			Gemfibrozil	311	35
IDEAL^Citation48	Coronary death or MI	2	Simvastatin	4,449	463
			Atorvastatin	4,439	411
LIPID^Citation49	Coronary death or MI	5-year median	Placebo	4,502	715
			Pravastatin	4,512	557
MIRACL^Citation50	Coronary death or MI	0.31	Placebo	1,548	169
			Atorvastatin	1,538	155
ORIGIN^Citation23	Cardiovascular death	6.2	Placebo	6,255	581
			Omega-3 fatty acids	6,281	574
PCABGT^Citation51	Fatal/non-fatal MI	4.3	Lovastatin 5 mg	675	40
			Lovastatin 80 mg	676	35
PLAC-I^Citation52	Coronary death or MI	3	Placebo	202	19
			Pravastatin	206	10
REGRESS^Citation53	Coronary death or MI	1	Placebo	434	16
			Pravastatin	450	9
STARS^Citation10	Coronary death or MI	3.25-year mean	Usual care	24	5
			Diet/cholestyramine	24	1
TNT^Citation54	Coronary death or MI	3	Atorvastatin 10 mg	5,006	418
			Atorvastatin 80 mg	4,995	334
VA-HIT^Citation55	Coronary death or MI	3	Placebo	1,267	275
			Gemfibrozil	1,264	219
Mixed primary and secondary preventiond
ACCORD^Citation24	Nonfatal MI or stroke, or CV death	5	Simvastatin/placebo	2,753	310
			Simvastatin/fenofibrate	2,765	291
HOLICOS-PAT^Citation26	Coronary death, MI, angina, revascularization	1	Diet only	749	37
			Pravastatin	1,290	58
HPS^Citation25	Coronary death or MI	3	Placebo	10,267	1212
			Simvastatin	10,269	898
PROSPER^Citation27	Coronary death or MI	0.25	Placebo	2,913	356
			Pravastatin	2,891	292

Notes:

a The timepoint is either a single time at which the lipid values were reported or, if indicated, the time over which the on-study mean or median was calculated

b ALLHAT-LLT had 14% of subjects with a history of coronary heart disease, but no indication of prior cardiovascular events, so was considered a primary prevention study. Patients in the SPARCL trial had had a stroke, but did not have coronary heart disease. Patients in ENHANCE were at increased risk due to elevated TC, but were primary with respect to cardiovascular events

c subjects in CARDS and FIELD had diabetes (a CHD risk equivalent), and were therefore classified with the secondary prevention studies. Subjects in ORIGIN were at high CV risk due to a history of CV events or diabetes

d populations were classified as mixed primary and secondary prevention if some subjects had a history cardiovascular events (36.5% in ACCORD, 41% in HPS), diabetes (13%–18% in Holicos-PAT), or vascular disease (44% in PROSPER, 17.5% in Holicos-PAT).

Abbreviations: 4S, Scandinavian Simvastatin Survival Study; ACCORD, Action to Control Cardiovascular Risk in Diabetes; AFCAPS/TexCAPS, Air Force/Texas Coronary Atherosceloris Prevention Study; AFREGS, Armed Forces Regression Study; AIM-HIGH, Atherothrombosis Intervention in Metabolic syndrome with low HDL/High triglycerides: Impact on Global Health outcomes; ALLHAT-LLT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; ALLIANCE, Aggressive Lipid-Lowering Initiation Abates New Cardiac Events; ASCOT-LLA, Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm; A-Z, A to Z Trial; BECAIT, BEzafibrate Coronary Atherosclerosis Intervention Trial; BIP, Bezafibrate Infarction Prevention; CARDS, Collaborative Atorvastatin Diabetes Study; CARE, Cholesterol and Recurrent Events; CHD, coronary heart disease; CV, cardiovascular; ENHANCE, Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression; FIELD, Fenofibrate Intervention and Event Lowering in Diabetes; GISSI-P. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico-Prevenzione; GREACE, GREek Atorvastatin and Coronary heart disease Evaluation; HATS, HDL Atherosclerosis Treatment Study; HERS, Heart and Estrogen/progestin Replacement Study; HHS, Helsinki Heart Study; Hollicos-PAT, Hokuriku lipid coronary heart disease study-pravastatin atherosclerosis trial; HPS, Heart Protection Study; IDEAL, Incremental Decrease in End points through Aggressive Lipid lowering; JUPITER, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; LIPID, Long-term Intervention with Pravastatin in Ischaemic Disease; LRC-CPPT, Lipid Research Clinics Coronary Primary Prevention Trial; MEGA, The Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese; METEOR, Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin; MI, myocardial infarction; MIRACL, Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering; NR, not reported; ORIGIN, Outcome Reduction with an Initial Glargine Iintervention; PCABGT, Post Coronary Artery Bypass Graft Trial; PLAC-I, Pravastatin Limitation of Atherosclerosis in the Coronary arteries; PROSPER, PROspective Study of Pravastatin in the Elderly at Risk; REGRESS, Regression Growth Evaluation Statin Study; SPARCL, Stroke Prevention by Aggressive Reduction in Cholesterol Levels; STARS, St Thomas’ Atherosclerosis Regression Study; TC, total cholesterol; TNT, Treating to New Targets; VA-HIT, Veterans Affairs High-density lipoprotein cholesterol Intervention Trial; WOSCOPS, West of Scotland Coronary Prevention Study.

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