{"slug":"hdl-cholesterol","name":"HDL cholesterol","aliases":["HDL-C","High-density lipoprotein cholesterol","Good cholesterol"],"kind":"biomarker","system":"metabolomics","unit":"mg/dL","unitNote":"To convert to mmol/L, divide by about 38.7.","answer":"In cohorts, mortality is lowest with HDL cholesterol in the middle, about 55 to 70 mg/dL in pooled data and 73 (men) to 93 (women) in Copenhagen, and rises again at both ends; but Mendelian randomization and four large drug trials show that raising HDL cholesterol does not lower heart risk, so the number is a marker of metabolic health, not a lever.","summary":"HDL cholesterol was called the good cholesterol because low values predict heart disease. Laboratories flag under 40 mg/dL in men and under 50 in women as low and 60 or more as high. The cohort curve is U-shaped, with higher mortality at very high values, and genes and trials agree that pushing the number up does not protect anyone.","whatItIs":[{"text":"HDL cholesterol measures the cholesterol carried inside high-density lipoprotein particles, the particles that accept cholesterol from macrophages, a key step in reverse cholesterol transport back to the liver. The ability of a person's HDL to do that job, called cholesterol efflux capacity, is only partly explained by the HDL cholesterol number: in healthy volunteers and in patients with and without angiographic coronary disease, HDL cholesterol and apolipoprotein A-I together accounted for less than 40 percent of the variation in efflux capacity.","cites":["khera2011","rohatgi2014"],"grade":"C"},{"text":"Low HDL cholesterol predicts coronary disease. Across 68 prospective studies with 302,430 people free of vascular disease, each 15 mg/dL higher HDL cholesterol carried a hazard ratio of 0.78 for coronary heart disease after adjustment, and the coronary event rate per 1,000 person-years was 6.4 in the bottom third of HDL versus 2.4 in the top third. That is an association across the usual range, not proof of cause.","cites":["erfc2009"],"grade":"A"},{"text":"HDL cholesterol travels with the rest of a person's metabolism. In the CANHEART cohort of 631,762 adults, people with lower HDL were more likely to have low incomes, unhealthy lifestyles, higher triglycerides and other cardiac risk factors, and low HDL predicted cancer and other non-cardiovascular deaths as strongly as cardiovascular deaths, which is why the authors concluded it is unlikely to be a cardiovascular-specific risk factor.","cites":["ko2016"],"grade":"B"}],"labRange":{"typical":"Under 40 mg/dL (men) or under 50 (women) flagged low; 60 or more flagged high, depending on the laboratory","claims":[{"text":"The cutoffs on most US reports come from the National Cholesterol Education Program's third Adult Treatment Panel (2001), which classed HDL cholesterol under 40 mg/dL as low, raised from under 35 in the previous panel, and 60 or more as high. In that scheme a value of 60 or above counted as a 'negative' risk factor that removed one risk factor from a person's count, which is the origin of the word 'protective' on laboratory reports.","cites":["ncep2001"],"grade":"A"},{"text":"The same panel's criteria for the metabolic syndrome use sex-specific cutoffs, HDL under 40 mg/dL in men and under 50 in women, alongside triglycerides of 150 or more, which is why many laboratories print a higher low cutoff for women. The panel stated that it did not specify a goal for raising HDL because the evidence was insufficient.","cites":["ncep2001"],"grade":"A"}]},"evidence":{"headline":"U-shaped in every large cohort: mortality lowest in the middle (about 55 to 70 mg/dL pooled; 73 in men and 93 in women in Copenhagen), higher below 40, and higher again above about 97 in men and 116 in women. Genetic studies and four drug trials found that raising HDL cholesterol does not reduce heart attacks.","scale":{"min":0,"max":140,"ticks":[0,20,40,60,80,100,120,140]},"bands":[{"label":"Low on laboratory reports (men under 40; women under 50)","low":0,"high":40,"tone":"lab","source":"NCEP ATP III 2001"},{"label":"Printed as high; once counted as a 'negative' risk factor","low":60,"high":140,"tone":"lab","source":"NCEP ATP III 2001"},{"label":"Higher cardiovascular, cancer and other mortality in cohorts","low":0,"high":40,"tone":"caution","source":"Ko 2016; Zhong 2020"},{"label":"Lowest all-cause (54 to 58) and cardiovascular (68 to 71) mortality, 37 cohorts","low":54,"high":71,"tone":"evidence","source":"Zhong 2020"},{"label":"Lowest all-cause mortality in Copenhagen: 73 in men, 93 in women","low":73,"high":93,"tone":"evidence","source":"Madsen 2017"},{"label":"Coronary risk stops falling above about 75 (women) to 90 (men)","low":75,"high":97,"tone":"neutral","source":"Wilkins 2014"},{"label":"Higher mortality: men from 97, women from 116; above 80 with coronary disease","low":97,"high":140,"tone":"caution","source":"Madsen 2017; Liu 2022"}],"claims":[{"text":"In the two Copenhagen population studies, 52,268 men and 64,240 women followed for 745,452 person-years, the association between HDL cholesterol and all-cause mortality was U-shaped in both sexes. Mortality was lowest at 73 mg/dL in men and 93 in women. Compared with those groups, men at 97 to 115 mg/dL had a hazard ratio of 1.36 and men at 116 or above 2.06; women at 116 to 134 had 1.10 and women at 135 or above 1.68. The authors called the finding paradoxical and asked for confirmation.","cites":["madsen2017"],"grade":"B"},{"text":"In Ontario's CANHEART cohort, 631,762 adults aged 40 to 105 without prior cardiovascular disease were followed for a mean of 4.9 years with 17,952 deaths. Lower HDL cholesterol carried higher cardiovascular, cancer and other mortality, and higher HDL, above 70 mg/dL in men and above 90 in women, carried higher non-cardiovascular mortality. Mean HDL in the cohort was 55.2.","cites":["ko2016"],"grade":"B"},{"text":"Pooling 37 prospective cohorts with 3,524,505 participants and more than 612,027 deaths, the dose-response curve was J-shaped. All-cause mortality was lowest at 54 to 58 mg/dL, cardiovascular mortality at 68 to 71 and cancer mortality at 64 to 68. Against a reference of 56, each 10 mg/dL higher carried a hazard ratio of 1.03 and each 10 lower 1.10; the highest category carried 1.21 and the lowest 1.36. The low end is the steeper side of the curve.","cites":["zhong2020"],"grade":"A"},{"text":"Very high HDL is not safer in people who already have coronary disease. Among 14,478 UK Biobank participants with coronary disease followed a median of 8.9 years, an HDL above 80 mg/dL carried a hazard ratio of 1.96 for death from any cause and 1.71 for cardiovascular death compared with 40 to 60, replicated in 5,467 Emory patients; the excess was larger in men (2.63) than women (1.39) and persisted after adjusting for a genetic HDL score. In 43,407 Japanese adults from nine cohorts, HDL of 90 or more carried a hazard ratio of 2.37 for atherosclerotic cardiovascular death, and the risk was more evident in current drinkers.","cites":["liu2022","hirata2018"],"grade":"B"},{"text":"In six US community cohorts (11,515 men and 12,925 women), coronary risk fell with rising HDL and then plateaued, with no further reduction above 90 mg/dL in men or 75 in women. Unadjusted total mortality was higher in men with very high HDL, but that excess shrank after adjusting for traditional risk factors, a reminder that the upper arm of the U may partly reflect who has a very high HDL rather than the HDL itself.","cites":["wilkins2014"],"grade":"B"},{"text":"Genes say HDL cholesterol is not the cause. A variant in the endothelial lipase gene that raises HDL by 0.14 mmol/L, tested in 20,913 heart-attack cases and 95,407 controls, should have cut heart-attack risk by 13 percent if HDL were causal; the observed odds ratio was 0.99. A score of 14 HDL-raising variants gave an odds ratio of 0.93 per standard deviation against 0.62 from observational data, while the LDL score behaved as expected (2.13). In Copenhagen, carriers of ABCA1 mutations with HDL 17 mg/dL lower had no excess ischemic heart disease (combined odds ratio 0.93), and a rare SCARB1 variant that raises HDL raised coronary risk, odds ratio 1.79.","cites":["voight2012","frikkeschmidt2008","zanoni2016"],"grade":"A"},{"text":"Drugs confirmed the genes. Four randomized trials of CETP inhibitors in 15,067, 15,871, 12,092 and 30,449 high-risk patients raised HDL cholesterol by 72 percent, 31 to 40 percent, 133 percent and 104 percent: the first raised cardiovascular events (hazard ratio 1.25) and death (1.58) and was stopped; the second and third were stopped for futility (hazard ratios 1.04 and 1.01); the fourth cut major coronary events by 9 percent (rate ratio 0.91) while also lowering non-HDL cholesterol by 17 mg/dL, which leaves open which change did the work. Two niacin trials in 3,414 and 25,673 patients raised HDL from a median of 35 to 42 mg/dL in one and by 6 mg/dL in the other, on top of a statin, and did not reduce events (hazard ratio 1.02; rate ratio 0.96), and the larger one increased serious adverse events.","cites":["barter2007","schwartz2012","lincoff2017","bowman2017","boden2011","landray2014"],"grade":"A"},{"text":"What HDL does may matter more than how much cholesterol it carries. In 2,924 Dallas adults followed for a median of 9.4 years, HDL cholesterol itself did not predict cardiovascular events after adjustment (hazard ratio 1.08), while the top quartile of cholesterol efflux capacity carried 67 percent lower risk than the bottom quartile (0.33) after accounting for HDL cholesterol and particle number. A meta-analysis of 18 observational studies confirmed lower efflux capacity in people with coronary disease (odds ratio 0.52 for high versus low) but found no clear link to cardiovascular mortality. Efflux capacity is a research assay, not a routine test.","cites":["rohatgi2014","cheng2022"],"grade":"B"}]},"levers":[{"name":"Aerobic exercise","effect":"raises it modestly","claim":{"text":"Across 25 randomized trials, aerobic training raised HDL cholesterol by a mean of 2.53 mg/dL. A minimum of about 120 minutes a week, or 900 kcal of exercise energy a week, was needed to see any rise, and each extra 10 minutes per session added about 1.4 mg/dL; frequency and intensity made no difference. The gain was larger in people with a body mass index under 28 or total cholesterol of 220 or more.","cites":["kodama2007"],"grade":"A"}},{"name":"Weight loss","effect":"raises it once weight is stable","claim":{"text":"Pooling 70 diet studies, each kilogram of weight lost raised HDL cholesterol by 0.009 mmol/L (about 0.35 mg/dL) once weight had stabilized; while weight was still falling, HDL dipped by 0.007 mmol/L per kilogram, so an HDL drawn mid-diet reads low.","cites":["dattilo1992"],"grade":"A"}},{"name":"Quitting smoking","effect":"raises it quickly","claim":{"text":"In 45 studies with 94 estimates of within-person change, HDL cholesterol rose after quitting by a weighted mean of 0.060 mmol/L (about 2.3 mg/dL), appearing within the first weeks and holding; continuing smokers and never-smokers showed no change over the same periods.","cites":["forey2013"],"grade":"B"}},{"name":"Replacing trans and saturated fat with unsaturated fat","effect":"improves the total-to-HDL ratio","claim":{"text":"In a meta-analysis of 60 controlled feeding trials, the total-to-HDL cholesterol ratio fell when cis-unsaturated fats replaced saturated fat, and the effect of replacing trans fat was almost twice as large. Swapping fat for carbohydrate did not improve the ratio and raised triglycerides.","cites":["mensink2003"],"grade":"A"}},{"name":"Alcohol","effect":"raises it without lowering heart risk","claim":{"text":"In 44 interventional studies alcohol raised HDL cholesterol by a pooled 0.094 mmol/L (about 3.6 mg/dL) with a dose-response trend. But in a Mendelian randomization of 261,991 people, carriers of a variant that cuts drinking by 17.2 percent had lower coronary risk (odds ratio 0.90) and lower ischemic stroke risk (0.83) across every level of consumption, so the HDL rise from alcohol does not translate into protection. In the Japanese cohorts the risk of a very high HDL was more evident in current drinkers.","cites":["brien2011","holmes2014","hirata2018"],"grade":"A"}},{"name":"HDL-raising medication","effect":"raises the number, not the outcome","claim":{"text":"Drugs that raise HDL cholesterol by 31 to 133 percent have not reduced cardiovascular events in randomized trials, and one raised mortality. The 2001 cholesterol panel set no HDL goal for that reason, and no later trial has supplied one. A low HDL is a reason to look at triglycerides, insulin, weight and ApoB, not a target in itself.","cites":["schwartz2012","lincoff2017","landray2014","ncep2001"],"grade":"A"}}],"caveats":[{"text":"A high HDL is not a credit against a high ApoB or LDL. The Mendelian randomization and trial data mean a person with a high HDL and a high particle count carries the risk of the particle count. The 'negative risk factor' rule that let a value of 60 or more cancel a risk factor dates from 2001 and predates every trial and genetic study above.","cites":["voight2012","ncep2001"],"grade":"A"},{"text":"The upper arm of the U is an association in cohorts, not a mechanism. Part of it shrinks after adjusting for risk factors, part of it is strongest in drinkers, and very high values can come from rare genetic variants as well as from drinking. A very high HDL is a question to answer, not a disease to treat.","cites":["wilkins2014","hirata2018","zanoni2016"],"grade":"B"},{"text":"Read HDL beside triglycerides. In 258 overweight, non-diabetic adults measured against a direct test of insulin action, a triglyceride-to-HDL ratio above 3.0 (in mg/dL units) identified insulin resistance with 64 percent sensitivity and 68 percent specificity, about as well as the metabolic syndrome criteria. A low HDL with high triglycerides usually means insulin resistance; fasting insulin settles it.","cites":["mclaughlin2003"],"grade":"C"},{"text":"The number means different things in men and women. Women run higher, and every cohort places the low-risk zone and the danger zone higher for women than men: 93 versus 73 for lowest mortality in Copenhagen, 90 versus 70 for excess non-cardiovascular death in CANHEART, 75 versus 90 for the coronary plateau in US cohorts. A single cutoff for both sexes misreads one of them.","cites":["madsen2017","ko2016","wilkins2014"],"grade":"B"}],"seeAPhysician":["An HDL cholesterol under about 40 mg/dL with triglycerides over about 150, especially with a rising waist or fasting glucose, which usually signals insulin resistance and belongs with a fasting insulin and an ApoB.","An HDL above about 100 in a man or 120 in a woman, particularly with a family history of early heart disease, heavy alcohol use, or abnormal liver tests.","A low HDL alongside a high ApoB or LDL cholesterol, or any lipid pattern in a parent or sibling with a heart attack, stroke or stent before 55 (men) or 65 (women).","Chest pressure, breathlessness on exertion, or calf pain when walking, regardless of the HDL number."],"openQuestions":["Whether the higher mortality at very high HDL cholesterol is caused by HDL, by dysfunctional HDL particles, or by the drinking, genetics and liver disease that travel with it; the cohorts cannot separate them and no trial can be run.","Whether HDL function (cholesterol efflux capacity) will become a clinical test; it predicts coronary disease independently of HDL cholesterol in cohorts, but the meta-analysis found no clear link to cardiovascular mortality and the assay is not standardized.","Why the fourth CETP inhibitor trial reduced coronary events by 9 percent when the first three did not; it also lowered non-HDL cholesterol by 17 mg/dL, so whether the HDL rise contributed anything is unknown.","Whether lifestyle rises in HDL (exercise, weight loss, quitting smoking) reduce events through HDL or only alongside it; the Mendelian randomization data argue the latter, and no trial has isolated the HDL component.","Where the practical ceiling sits for a healthy adult; cohorts put higher risk above about 97 in men and 116 in women, with no study of what to do about a value in between."],"questions":[{"q":"Is an HDL of 90 too high?","a":"For a woman, 90 sits at the lowest-mortality point in the Copenhagen cohorts (93); for a man it is above that point (73) and inside the CANHEART zone where non-cardiovascular deaths rose (above 70). Neither is a danger zone, but a very high HDL stops being protective, and with heavy drinking, liver disease or a family history of early heart disease it deserves a conversation. The particle count (ApoB) carries the heart risk either way."},{"q":"What is an optimal HDL level?","a":"No trial has set one. Pooled cohorts put the lowest all-cause mortality at 54 to 58 mg/dL and the lowest cardiovascular mortality at 68 to 71; the Copenhagen studies put it at 73 in men and 93 in women. Risk rises below 40 and again above about 97 (men) or 116 (women). Those are associations: the genetic and trial evidence says the HDL number is a readout of metabolic health rather than something to raise for its own sake."},{"q":"Does raising HDL lower heart risk?","a":"Not by any means tested so far. Four randomized trials of drugs that raised HDL cholesterol by 31 to 133 percent did not reduce events except where the drug also lowered non-HDL cholesterol, two niacin trials failed, and genetic variants that raise HDL do not lower heart-attack risk. Exercise, weight loss and quitting smoking raise HDL a few mg/dL and are worth doing for every other reason."}],"citations":[{"id":"khera2011","authors":"Khera AV, Cuchel M, de la Llera-Moya M, et al.","title":"Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis","journal":"New England Journal of Medicine","year":2011,"pmid":"21226578","doi":"10.1056/NEJMoa1001689","type":"cross-sectional","finding":"HDL cholesterol and apoA-I explained less than 40 percent of the variation in cholesterol efflux capacity; efflux predicted coronary disease independently of HDL cholesterol.","url":"https://pubmed.ncbi.nlm.nih.gov/21226578/"},{"id":"erfc2009","authors":"Emerging Risk Factors Collaboration; Di Angelantonio E, Sarwar N, et al.","title":"Major lipids, apolipoproteins, and risk of vascular disease","journal":"JAMA","year":2009,"pmid":"19903920","doi":"10.1001/jama.2009.1619","type":"meta-analysis","finding":"Hazard ratio 0.78 for coronary heart disease per 15 mg/dL higher HDL cholesterol across 302,430 people in 68 cohorts.","url":"https://pubmed.ncbi.nlm.nih.gov/19903920/"},{"id":"ko2016","authors":"Ko DT, Alter DA, Guo H, et al.","title":"High-density lipoprotein cholesterol and cause-specific mortality in individuals without previous cardiovascular conditions: the CANHEART study","journal":"Journal of the American College of Cardiology","year":2016,"pmid":"27810046","doi":"10.1016/j.jacc.2016.08.038","type":"cohort","finding":"In 631,762 adults, low HDL predicted cardiovascular, cancer and other deaths alike; HDL above 70 (men) and 90 (women) carried higher non-cardiovascular mortality.","url":"https://pubmed.ncbi.nlm.nih.gov/27810046/"},{"id":"ncep2001","authors":"Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults","title":"Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)","journal":"JAMA","year":2001,"pmid":"11368702","doi":"10.1001/jama.285.19.2486","type":"guideline","finding":"HDL under 40 mg/dL low, 60 or more high and a 'negative' risk factor; metabolic syndrome cutoffs under 40 (men) and under 50 (women); no goal set for raising HDL.","url":"https://pubmed.ncbi.nlm.nih.gov/11368702/"},{"id":"madsen2017","authors":"Madsen CM, Varbo A, Nordestgaard BG","title":"Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies","journal":"European Heart Journal","year":2017,"pmid":"28419274","doi":"10.1093/eurheartj/ehx163","type":"cohort","finding":"U-shaped mortality curve in 52,268 men and 64,240 women; lowest at 73 mg/dL in men and 93 in women; hazard ratio 2.06 for men at 116 or above and 1.68 for women at 135 or above.","url":"https://pubmed.ncbi.nlm.nih.gov/28419274/"},{"id":"zhong2020","authors":"Zhong GC, Huang SQ, Peng Y, et al.","title":"HDL-C is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response fashion: a pooled analysis of 37 prospective cohort studies","journal":"European Journal of Preventive Cardiology","year":2020,"pmid":"32283957","doi":"10.1177/2047487320914756","type":"meta-analysis","finding":"In 3,524,505 people, lowest all-cause mortality at 54 to 58 mg/dL and cardiovascular mortality at 68 to 71; both extremes carried higher risk.","url":"https://pubmed.ncbi.nlm.nih.gov/32283957/"},{"id":"liu2022","authors":"Liu C, Dhindsa D, Almuwaqqat Z, et al.","title":"Association between high-density lipoprotein cholesterol levels and adverse cardiovascular outcomes in high-risk populations","journal":"JAMA Cardiology","year":2022,"pmid":"35583863","doi":"10.1001/jamacardio.2022.0912","type":"cohort","finding":"In 14,478 UK Biobank and 5,467 Emory patients with coronary disease, HDL above 80 mg/dL carried hazard ratio 1.96 for all-cause and 1.71 for cardiovascular death versus 40 to 60.","url":"https://pubmed.ncbi.nlm.nih.gov/35583863/"},{"id":"hirata2018","authors":"Hirata A, Sugiyama D, Watanabe M, et al.","title":"Association of extremely high levels of high-density lipoprotein cholesterol with cardiovascular mortality in a pooled analysis of 9 cohort studies including 43,407 individuals: the EPOCH-JAPAN study","journal":"Journal of Clinical Lipidology","year":2018,"pmid":"29506864","doi":"10.1016/j.jacl.2018.01.014","type":"cohort","finding":"HDL of 90 mg/dL or more carried hazard ratio 2.37 for atherosclerotic cardiovascular death; the risk was more evident in current drinkers.","url":"https://pubmed.ncbi.nlm.nih.gov/29506864/"},{"id":"wilkins2014","authors":"Wilkins JT, Ning H, Stone NJ, et al.","title":"Coronary heart disease risks associated with high levels of HDL cholesterol","journal":"Journal of the American Heart Association","year":2014,"pmid":"24627418","doi":"10.1161/JAHA.113.000519","type":"cohort","finding":"No further fall in coronary risk above 90 mg/dL in men or 75 in women across six US cohorts; excess mortality at very high HDL attenuated after adjustment.","url":"https://pubmed.ncbi.nlm.nih.gov/24627418/"},{"id":"voight2012","authors":"Voight BF, Peloso GM, Orho-Melander M, et al.","title":"Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study","journal":"Lancet","year":2012,"pmid":"22607825","doi":"10.1016/S0140-6736(12)60312-2","type":"mendelian-randomization","finding":"Genetic variants that raise HDL cholesterol did not lower heart-attack risk (odds ratio 0.99 for LIPG; 0.93 per SD for a 14-variant score) while LDL variants did.","url":"https://pubmed.ncbi.nlm.nih.gov/22607825/"},{"id":"frikkeschmidt2008","authors":"Frikke-Schmidt R, Nordestgaard BG, Stene MC, et al.","title":"Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease","journal":"JAMA","year":2008,"pmid":"18523221","doi":"10.1001/jama.299.21.2524","type":"mendelian-randomization","finding":"Carriers with HDL 17 mg/dL lower had no excess ischemic heart disease (combined odds ratio 0.93) in 41,961 Danes.","url":"https://pubmed.ncbi.nlm.nih.gov/18523221/"},{"id":"zanoni2016","authors":"Zanoni P, Khetarpal SA, Larach DB, et al.","title":"Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease","journal":"Science","year":2016,"pmid":"26965621","doi":"10.1126/science.aad3517","type":"mendelian-randomization","finding":"A SCARB1 P376L variant that raises HDL cholesterol raised coronary heart disease risk, odds ratio 1.79.","url":"https://pubmed.ncbi.nlm.nih.gov/26965621/"},{"id":"barter2007","authors":"Barter PJ, Caulfield M, Eriksson M, et al.","title":"Effects of torcetrapib in patients at high risk for coronary events","journal":"New England Journal of Medicine","year":2007,"pmid":"17984165","doi":"10.1056/NEJMoa0706628","type":"rct","finding":"In 15,067 patients a CETP inhibitor raised HDL 72.1 percent and raised cardiovascular events (HR 1.25) and death (HR 1.58); the trial was stopped.","url":"https://pubmed.ncbi.nlm.nih.gov/17984165/"},{"id":"schwartz2012","authors":"Schwartz GG, Olsson AG, Abt M, et al.","title":"Effects of dalcetrapib in patients with a recent acute coronary syndrome","journal":"New England Journal of Medicine","year":2012,"pmid":"23126252","doi":"10.1056/NEJMoa1206797","type":"rct","finding":"In 15,871 patients HDL rose 31 to 40 percent with no change in events (HR 1.04); stopped for futility.","url":"https://pubmed.ncbi.nlm.nih.gov/23126252/"},{"id":"lincoff2017","authors":"Lincoff AM, Nicholls SJ, Riesmeyer JS, et al.","title":"Evacetrapib and cardiovascular outcomes in high-risk vascular disease","journal":"New England Journal of Medicine","year":2017,"pmid":"28514624","doi":"10.1056/NEJMoa1609581","type":"rct","finding":"In 12,092 patients HDL rose 133.2 percent with no reduction in events (HR 1.01); stopped for lack of efficacy.","url":"https://pubmed.ncbi.nlm.nih.gov/28514624/"},{"id":"bowman2017","authors":"HPS3/TIMI55-REVEAL Collaborative Group; Bowman L, Hopewell JC, et al.","title":"Effects of anacetrapib in patients with atherosclerotic vascular disease","journal":"New England Journal of Medicine","year":2017,"pmid":"28847206","doi":"10.1056/NEJMoa1706444","type":"rct","finding":"In 30,449 patients HDL was 43 mg/dL higher (104 percent) and non-HDL 17 mg/dL lower; major coronary events fell 9 percent (rate ratio 0.91).","url":"https://pubmed.ncbi.nlm.nih.gov/28847206/"},{"id":"boden2011","authors":"AIM-HIGH Investigators; Boden WE, Probstfield JL, et al.","title":"Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy","journal":"New England Journal of Medicine","year":2011,"pmid":"22085343","doi":"10.1056/NEJMoa1107579","type":"rct","finding":"In 3,414 patients niacin raised median HDL from 35 to 42 mg/dL with no clinical benefit (HR 1.02); stopped for lack of efficacy.","url":"https://pubmed.ncbi.nlm.nih.gov/22085343/"},{"id":"landray2014","authors":"HPS2-THRIVE Collaborative Group; Landray MJ, Haynes R, et al.","title":"Effects of extended-release niacin with laropiprant in high-risk patients","journal":"New England Journal of Medicine","year":2014,"pmid":"25014686","doi":"10.1056/NEJMoa1300955","type":"rct","finding":"In 25,673 patients HDL was 6 mg/dL higher with no reduction in major vascular events (rate ratio 0.96) and more serious adverse events.","url":"https://pubmed.ncbi.nlm.nih.gov/25014686/"},{"id":"rohatgi2014","authors":"Rohatgi A, Khera A, Berry JD, et al.","title":"HDL cholesterol efflux capacity and incident cardiovascular events","journal":"New England Journal of Medicine","year":2014,"pmid":"25404125","doi":"10.1056/NEJMoa1409065","type":"cohort","finding":"In 2,924 Dallas adults HDL cholesterol did not predict events (HR 1.08) while top-quartile efflux capacity carried 67 percent lower risk (HR 0.33).","url":"https://pubmed.ncbi.nlm.nih.gov/25404125/"},{"id":"cheng2022","authors":"Cheng W, Rosolowski M, Boettner J, et al.","title":"High-density lipoprotein cholesterol efflux capacity and incidence of coronary artery disease and cardiovascular mortality: a systematic review and meta-analysis","journal":"Lipids in Health and Disease","year":2022,"pmid":"35643463","doi":"10.1186/s12944-022-01657-3","type":"meta-analysis","finding":"Across 18 observational studies high efflux capacity carried odds ratio 0.52 for coronary disease, independent of HDL cholesterol, with no clear association with cardiovascular mortality.","url":"https://pubmed.ncbi.nlm.nih.gov/35643463/"},{"id":"mclaughlin2003","authors":"McLaughlin T, Abbasi F, Cheal K, et al.","title":"Use of metabolic markers to identify overweight individuals who are insulin resistant","journal":"Annals of Internal Medicine","year":2003,"pmid":"14623617","doi":"10.7326/0003-4819-139-10-200311180-00007","type":"cross-sectional","finding":"A triglyceride-to-HDL ratio cut-point of 3.0 identified insulin resistance with 64 percent sensitivity and 68 percent specificity in 258 overweight adults.","url":"https://pubmed.ncbi.nlm.nih.gov/14623617/"},{"id":"kodama2007","authors":"Kodama S, Tanaka S, Saito K, et al.","title":"Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: a meta-analysis","journal":"Archives of Internal Medicine","year":2007,"pmid":"17533202","doi":"10.1001/archinte.167.10.999","type":"meta-analysis","finding":"Across 25 randomized trials aerobic exercise raised HDL by 2.53 mg/dL; a minimum of 120 minutes or 900 kcal a week was needed; each extra 10 minutes per session added about 1.4 mg/dL.","url":"https://pubmed.ncbi.nlm.nih.gov/17533202/"},{"id":"dattilo1992","authors":"Dattilo AM, Kris-Etherton PM","title":"Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis","journal":"American Journal of Clinical Nutrition","year":1992,"pmid":"1386186","doi":"10.1093/ajcn/56.2.320","type":"meta-analysis","finding":"Across 70 studies HDL rose 0.009 mmol/L per kilogram lost at stabilized weight and fell 0.007 mmol/L per kilogram during active weight loss.","url":"https://pubmed.ncbi.nlm.nih.gov/1386186/"},{"id":"forey2013","authors":"Forey BA, Fry JS, Lee PN, Thornton AJ, Coombs KJ","title":"The effect of quitting smoking on HDL-cholesterol: a review based on within-subject changes","journal":"Biomarker Research","year":2013,"pmid":"24252691","doi":"10.1186/2050-7771-1-26","type":"review","finding":"Across 45 studies, quitting smoking raised HDL by a weighted mean 0.060 mmol/L, rapidly after quitting.","url":"https://pubmed.ncbi.nlm.nih.gov/24252691/"},{"id":"mensink2003","authors":"Mensink RP, Zock PL, Kester AD, Katan MB","title":"Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials","journal":"American Journal of Clinical Nutrition","year":2003,"pmid":"12716665","doi":"10.1093/ajcn/77.5.1146","type":"meta-analysis","finding":"The total-to-HDL ratio fell when cis-unsaturated fat replaced saturated fat; replacing trans fat had almost twice the effect; carbohydrate did not help and raised triglycerides.","url":"https://pubmed.ncbi.nlm.nih.gov/12716665/"},{"id":"brien2011","authors":"Brien SE, Ronksley PE, Turner BJ, Mukamal KJ, Ghali WA","title":"Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies","journal":"BMJ","year":2011,"pmid":"21343206","doi":"10.1136/bmj.d636","type":"meta-analysis","finding":"Alcohol raised HDL cholesterol by a pooled 0.094 mmol/L with a dose-response trend across 44 interventional studies.","url":"https://pubmed.ncbi.nlm.nih.gov/21343206/"},{"id":"holmes2014","authors":"Holmes MV, Dale CE, Zuccolo L, et al.","title":"Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data","journal":"BMJ","year":2014,"pmid":"25011450","doi":"10.1136/bmj.g4164","type":"mendelian-randomization","finding":"In 261,991 people, a variant that lowers drinking by 17.2 percent carried lower coronary (OR 0.90) and ischemic stroke (OR 0.83) risk across all levels of consumption.","url":"https://pubmed.ncbi.nlm.nih.gov/25011450/"}],"written":"2026-10-07","updated":"2026-10-07","reviewed":true,"reviewedOn":"2026-10-10","related":{"essays":["testosterone-200-apob-120-what-a-chatbot-cannot-do","fasting-insulin-of-12-what-it-means","how-alcohol-affects-your-epigenetic-health"],"glossary":["ApoB","Insulin resistance","Fasting insulin","Reference range","Optimal range"],"symptoms":["high-cholesterol","weight-loss-resistance"],"entries":["apob","triglycerides","fasting-insulin"]},"url":"https://taggehealth.com/labs/hdl-cholesterol","author":"Daniel Tagge, MD","publisher":"Tagge Health","license":"Free to read and cite with attribution to the URL above.","inPractice":"I read HDL as a report on metabolism, not as a target. I like to see it between about 50 and 80 in men and about 50 and 90 in women, which is where the Copenhagen cohort found mortality lowest, read beside triglycerides, fasting insulin and ApoB. A low HDL with high triglycerides tells me to look for insulin resistance; I do not try to raise the HDL, I treat the cause and watch it follow. A very high HDL, over about 100, does not reassure me: the cohorts say risk climbs there, especially in men and in drinkers, and I ask about alcohol and liver before I say anything about heart health. The number that carries the heart risk is ApoB."}