今日の臨床サポート

高中性脂肪(トリグリセライド)血症

著者: 辻本哲郎 虎の門病院分院 糖尿病内分泌科

監修: 野田光彦 国際医療福祉大学市川病院 糖尿病・代謝・内分泌内科

著者校正/監修レビュー済:2021/05/12
参考ガイドライン:
  1. 日本動脈硬化学会:動脈硬化性疾患予防ガイドライン2017年版
患者向け説明資料

概要・推奨   

  1. 高TG血症は検証の余地が残るものの、動脈硬化性疾患、特に冠動脈疾患と関連していることが数多く報告されている。
  1. 高TG血症は、動脈硬化に関連する他の危険因子を同時に伴うことが多く、十分に評価し適宜対応する(推奨度1)。
  1. TG値≧500mg/dlの著明な高TG血症の場合は、動脈硬化以外にも急性膵炎の発症に注意して診療にあたる必要がある(推奨度1)。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
辻本哲郎 : 特に申告事項無し[2021年]
監修:野田光彦 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行った(変更なし)。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 高中性脂肪(トリグリセライド)血症(以下、高TG血症)は、10時間以上の空腹時採血の結果、TG値≧150mg/dlを確認して診断する。
  1. 脂質異常症:スクリーニングのための診断基準(空腹時採血)
  1. LDLコレステロール
  1. 140 mg/dl以上:高LDLコレステロール血症
  1. 120~139 mg/dl:境界域高LDLコレステロール血症*
  1. HDLコレステロール
  1. 40 mg/dl未満:低HDLコレステロール血症
  1. トリグリセライド
  1. 150 mg/dl以上:高トリグリセライド血症
 
  1. LDLコレステロールはFriedewald(TC - HDL-C -TG/5)の式で計算する(TGが400 mg/dl未満の場合)。
  1. TGが400 mg/dl以上や食後採血の場合には non HDL-C(TC -HDL-C)を使用し、その基準はLDL-C +30 mg/dlとする。
  1. 10~12時間以上の絶食を「空腹時」とする。ただし、水やお茶などカロリーのない水分の摂取は可とする。
  1. *:スクリーニングで境界域高LDLコレステロール血症を示した場合は、高リスク病態がないか検討し、治療の必要性を考慮する。
 
(引用:日本動脈硬化学会(編):動脈硬化性疾患予防ガイドライン2017年版. 日本動脈硬化学会, 2017)
  1. 高TG血症には、体質や遺伝子異常に基づいて発症した原発性(一次性)と、飲酒、肥満、薬剤、糖尿病などによる続発性(二次性)がある。
  1. 食事由来のカイロミクロンや、肝で生成される超低比重リポ蛋白(VLDL)にTGは多く含まれ、血中のTG値はそれらの影響を強く受ける。食事由来のカイロミクロンの増加、アルコールや糖質の過剰摂取によるVLDLの産生増加、糖尿病でインスリン作用不足の状態でリポ蛋白リパーゼ(LPL)作用が低下することによるVLDLやカイロミクロンの代謝遅延、などいずれも高TG血症につながる。
  1. 高TG血症は検証の余地が残るものの、動脈硬化性疾患、特に冠動脈疾患と関連していることが欧米を中心に数多く報告されており[1]、冠動脈疾患の発症頻度が欧米より低いわが国でもTG値と冠動脈疾患の発症率が正相関するとの報告が多い[2]
  1. 高TG血症に対する主な治療目標は、心血管疾患の進展・発症を予防するためである。すべての症例において、TG値<150mg/dlとすることが勧められる。
  1. TG値、総コレステロール(TC)値、HDLコレステロール(HDL-C)値からLDLコレステロール(LDL-C)値も評価し、冠動脈疾患のリスクに応じて治療方針を決定する。
  1. 高TG血症の治療アルゴリズム:図アルゴリズム
  1. 高TG血症は動脈硬化との関連が指摘されているレムナントリポ蛋白の増加[3]、small dense LDL-Cの増加[4]、HDL-Cの低下[5]、インスリン抵抗性[6]などを伴いやすい。
  1. 高TG血症、低HDLコレステロール血症といった脂質異常を伴う病態にメタボリックシンドロームがあり、心血管疾患の成因として重要であり、内臓脂肪蓄積や肥満にも注意して診察する[7]
  1. 著明な高TG血症は、急性膵炎の発症リスクを上昇させるため、TG値≧500mg/dlの際はTG値を積極的に低下させることが推奨される[8][9]
  1. Non HDL-C値(TC値-HDL-C値)は、レムナントリポ蛋白やLDL-Cなどの動脈硬化惹起性のコレステロールを含み、管理目標LDL-C値+30(mg/dl)を指標に治療方針の参考にすることができる。Non HDL-C値の管理目標は、高TG血症の場合にLDL-C値の管理目標を達成した後の二次目標であるが、TG値≧400mg/dlおよび食後採血の場合はnon HDL-C値を指標にする。
問診・診察のポイント  
  1. 基本的に、自覚症状は認めない。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: Nadeem Sarwar, John Danesh, Gudny Eiriksdottir, Gunnar Sigurdsson, Nick Wareham, Sheila Bingham, S Matthijs Boekholdt, Kay-Tee Khaw, Vilmundur Gudnason
雑誌名: Circulation. 2007 Jan 30;115(4):450-8. doi: 10.1161/CIRCULATIONAHA.106.637793. Epub 2006 Dec 26.
Abstract/Text BACKGROUND: Many epidemiological studies have reported on associations between serum triglyceride concentrations and the risk of coronary heart disease, but this association has not been reliably quantified. In the present study, we report 2 separate nested case-control comparisons in 2 different prospective, population-based cohorts, plus an updated meta-analysis of 27 additional prospective studies in general Western populations.
METHODS AND RESULTS: Measurements were made in a total of 3582 incident cases of fatal and nonfatal coronary heart disease and 6175 controls selected from among the 44,237 men and women screened in the Reykjavik and the European Prospective Investigation of Cancer (EPIC)-Norfolk studies. Repeat measurements were obtained an average of 4 years apart in 1933 participants in the EPIC-Norfolk Study and an average of 12 years apart in 379 participants in the Reykjavik study. The long-term stability of log-triglyceride values (within-person correlation coefficients of 0.64 [95% CI, 0.60 to 0.68] over 4 years and 0.63 [95% CI, 0.57 to 0.70] over 12 years) was similar to those of blood pressure and total serum cholesterol. After adjustment for baseline values of several established risk factors, the strength of the association was substantially attenuated, and the adjusted odds ratio for coronary heart disease was 1.76 (95% CI, 1.39 to 2.21) in the Reykjavik study and 1.57 (95% CI, 1.10 to 2.24) in the EPIC-Norfolk study in a comparison of individuals in the top third with those in the bottom third of usual log-triglyceride values. Similar overall findings (adjusted odds ratio, 1.72; 95% CI, 1.56 to 1.90) were observed in an updated meta-analysis involving a total of 10,158 incident coronary heart disease cases from 262,525 participants in 29 studies.
CONCLUSIONS: Available prospective studies in Western populations consistently indicate moderate and highly significant associations between triglyceride values and coronary heart disease risk. Because these associations depend considerably on levels of established risk factors, however, further studies are needed to help assess the nature of any independent associations.

PMID 17190864  Circulation. 2007 Jan 30;115(4):450-8. doi: 10.1161/CIR・・・
著者: H Iso, Y Naito, S Sato, A Kitamura, T Okamura, T Sankai, T Shimamoto, M Iida, Y Komachi
雑誌名: Am J Epidemiol. 2001 Mar 1;153(5):490-9.
Abstract/Text To examine the relation of triglycerides with coronary heart disease among populations with low mean total cholesterol, the authors conducted a 15.5-year prospective study ending in 1997 of 11,068 Japanese aged 40-69 years (4,452 men and 6,616 women with mean total cholesterol = 4.73 mmol/liter and 5.03 mmol/liter, respectively), initially free of coronary heart disease or stroke. There were 236 coronary heart disease events comprising 133 myocardial infarctions, 68 angina pectoris events, and 44 sudden cardiac deaths. The coronary heart disease incidence was greater in a dose-response manner across increasing quartiles of nonfasting triglycerides for both sexes. The multivariate relative risk of coronary heart disease adjusting for coronary risk factors and time since last meal associated with a 1-mmol/liter increase in triglycerides was 1.29 (95% confidence interval (CI): 1.09, 1.53; p = 0.004) for men and 1.42 (95% CI: 1.15, 1.75; p = 0.001) for women. The trend was similar for myocardial infarction, angina pectoris, and sudden cardiac death. The relation of triglycerides with coronary heart disease was not influenced materially by total cholesterol levels or, in a subsample analysis (51% of total sample), by high density lipoprotein cholesterol levels. Nonfasting serum triglycerides predict the incidence of coronary heart disease among Japanese men and women who possess low mean values of total cholesterol. Further adjustment for high density lipoprotein cholesterol suggests an independent role of triglycerides on the coronary heart disease risk.

PMID 11226981  Am J Epidemiol. 2001 Mar 1;153(5):490-9.
著者: H Fukushima, K Kugiyama, S Sugiyama, O Honda, S Koide, S Nakamura, H Kawano, H Soejima, S Miyamoto, M Yoshimura, T Sakamoto, H Ogawa
雑誌名: Am J Cardiol. 2001 Dec 15;88(12):1370-3.
Abstract/Text It is known that hypertriglyceridemia is a risk factor of coronary artery disease (CAD) in postmenopausal women. This study prospectively examined whether remnant lipoprotein, an atherogenic triglyceride-rich lipoprotein, may have a significant risk and prognostic values in postmenopausal women with angiographically verified CAD. Remnant-like lipoprotein particles cholesterol (RLP cholesterol) levels in fasting serum were measured in 134 consecutive postmenopausal women with (n = 56) or without (n = 78) CAD by an immunoseparation method. The women with CAD were followed for < or =24 months until occurrence of the following clinical coronary events: readmission or coronary revascularization due to recurrent or refractory angina pectoris, nonfatal myocardial infarction, and cardiac death. Multivariate logistic regression analysis showed that high RLP cholesterol levels (>5.7 mg/dl cholesterol; 90th percentile of the distribution of RLP cholesterol levels in controls) were a significant risk factor for the presence of CAD independent of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and other traditional risk factors. Kaplan-Meier analysis demonstrated that women with CAD and higher RLP cholesterol levels had a significantly higher probability of developing coronary events (p <0.001). In multivariate Cox hazard analysis, high RLP cholesterol levels as well as diabetes and hypercholesterolemia were a significant predictor of future coronary events independent of other risk factors in women with CAD (odds ratio 9.7, 95% confidence intervals 1.3 to 20.3, p = 0.02). In conclusion, increased levels of RLP cholesterol are a significant and independent risk factor of CAD and predict future coronary events in postmenopausal women with CAD.

PMID 11741554  Am J Cardiol. 2001 Dec 15;88(12):1370-3.
著者: B D Miller, E L Alderman, W L Haskell, J M Fair, R M Krauss
雑誌名: Circulation. 1996 Nov 1;94(9):2146-53.
Abstract/Text BACKGROUND: LDL particles differ in size and density. Individuals with LDL profiles that peak in relatively small, dense particles have been reported to be at increased risk of coronary artery disease. We hypothesized that response to coronary disease therapy in such individuals might differ from response in individuals whose profiles peak in larger, more buoyant LDL. We examined this hypothesis in the Stanford Coronary Risk Intervention Project, an angiographic trial that compared multifactorial risk-reduction intervention with the usual care of physicians.
METHODS AND RESULTS: For 213 men, a bimodal frequency distribution of peak LDL density (g/mL) determined by analytical ultracentrifugation was used to classify baseline LDL profiles as "buoyant mode" (density < or = 1.0378) or "dense mode" (density > 1.0378). Coronary disease progression after 4 years was assessed by rates of change (mm/y, negative when arteries narrow) of minimum artery diameter. Rates for buoyant-mode subjects were -0.038 +/- 0.007 (mean +/- SEM) in usual care (n = 65) and -0.039 +/- 0.010 in intervention (n = 56; P = .6). Rates for dense-mode subjects were -0.054 +/- 0.012 in usual care (n = 51) and -0.008 +/- 0.009 in intervention (n = 41, P = .007). Lipid changes did not account for this difference in angiographic response.
CONCLUSIONS: Different types of LDL profile may predict different-responses to specific therapies, perhaps because metabolic processes determine both LDL profiles and responses to therapies.

PMID 8901665  Circulation. 1996 Nov 1;94(9):2146-53.
著者: D L Sprecher, B V Harris, E A Stein, P S Bellet, L M Keilson, L A Simbartl
雑誌名: Circulation. 1996 Dec 15;94(12):3239-45.
Abstract/Text BACKGROUND: Heterozygous lipoprotein lipase (LPL) deficiency has been associated with familial hypertriglyceridemia and familial combined hyperlipidemia. Studies of heterozygotes with LPL gene defects at amino acid residues 188 and 207 showed higher triglycerides (TG) and lower HDL cholesterol (HDL-C), with no elevation in LDL cholesterol (LDL-C). Other LPL defects may reveal alternate clinical phenotypes.
METHODS AND RESULTS: We evaluated three families with defects at amino acid residues 64, 194, and 188. Thirty-eight heterozygotes (8 with defect 64, 14 with defect 194, and 16 with defect 188) and 95 family members without defects were studied. Plasma lipid, lipoprotein, and apolipoprotein (apo) values were measured, as well as blood pressure. Pooled carriers demonstrated higher systolic blood pressure (SBP) (127 versus 116 mm Hg, P < .0001) and TG (160 versus 125 mg/dL, P = .004) and lower HDL-C (44 versus 52 mg/dL, P = .001) than did noncarriers. A comparison of the 188 carriers and noncarriers revealed the most striking phenotypic characteristics, with lower HDL-C (36 versus 51 mg/dL, P < .0001) and HDL-C/(apo A-I + apo A-II) (0.21 versus 0.24, P = .002) and higher TG (206 versus 123 mg/dL, P = .0003), SBP (132 versus 116 mm Hg, P = .0004), and apo B/LDL-C (1.12 versus 0.93, P < .0001).
CONCLUSIONS: These data confirm past observations that LPL deficient heterozygotes trend toward lower HDL-C and higher TG levels while potentially expressing higher SBP. These data also implicate the specific LPL gene defect as a contributing factor to the variable expression of HDL-C, TG, and SBP.

PMID 8989135  Circulation. 1996 Dec 15;94(12):3239-45.
著者: Tracey McLaughlin, Fahim Abbasi, Karen Cheal, James Chu, Cindy Lamendola, Gerald Reaven
雑誌名: Ann Intern Med. 2003 Nov 18;139(10):802-9.
Abstract/Text BACKGROUND: Insulin resistance is more common in overweight individuals and is associated with increased risk for type 2 diabetes mellitus and cardiovascular disease. Given the current epidemic of obesity and the fact that lifestyle interventions, such as weight loss and exercise, decrease insulin resistance, a relatively simple means to identify overweight individuals who are insulin resistant would be clinically useful.
OBJECTIVE: To evaluate the ability of metabolic markers associated with insulin resistance and increased risk for cardiovascular disease to identify the subset of overweight individuals who are insulin resistant.
DESIGN: Cross-sectional study.
SETTING: General clinical research center.
PATIENTS: 258 nondiabetic, overweight volunteers.
MEASUREMENTS: Body mass index; fasting glucose, insulin, lipid and lipoprotein concentrations; and insulin-mediated glucose disposal as quantified by the steady-state plasma glucose concentration during the insulin suppression test. Overweight was defined as body mass index of 25 kg/m2 or greater, and insulin resistance was defined as being in the top tertile of steady-state plasma glucose concentrations. Receiver-operating characteristic curve analysis was used to identify the best markers of insulin resistance; optimal cut-points were identified and analyzed for predictive power.
RESULTS: Plasma triglyceride concentration, ratio of triglyceride to high-density lipoprotein cholesterol concentrations, and insulin concentration were the most useful metabolic markers in identifying insulin-resistant individuals. The optimal cut-points were 1.47 mmol/L (130 mg/dL) for triglyceride, 1.8 in SI units (3.0 in traditional units) for the triglyceride-high-density lipoprotein cholesterol ratio, and 109 pmol/L for insulin. Respective sensitivity and specificity for these cut-points were 67%, 64%, and 57% and 71%, 68%, and 85%. Their ability to identify insulin-resistant individuals was similar to the ability of the criteria proposed by the Adult Treatment Panel III to diagnose the metabolic syndrome (sensitivity, 52%, and specificity, 85%).
CONCLUSIONS: Three relatively simple metabolic markers can help identify overweight individuals who are sufficiently insulin resistant to be at increased risk for various adverse outcomes. In the absence of a standardized insulin assay, we suggest that the most practical approach to identify overweight individuals who are insulin resistant is to use the cut-points for either triglyceride concentration or the triglyceride-high-density lipoprotein cholesterol concentration ratio.

PMID 14623617  Ann Intern Med. 2003 Nov 18;139(10):802-9.
著者: Apoor S Gami, Brandi J Witt, Daniel E Howard, Patricia J Erwin, Lisa A Gami, Virend K Somers, Victor M Montori
雑誌名: J Am Coll Cardiol. 2007 Jan 30;49(4):403-14. doi: 10.1016/j.jacc.2006.09.032. Epub 2007 Jan 12.
Abstract/Text OBJECTIVES: The purpose of this research was to assess the association between the metabolic syndrome (MetSyn) and cardiovascular events and mortality by meta-analyses of longitudinal studies.
BACKGROUND: Controversy exists regarding the cardiovascular risk associated with MetSyn.
METHODS: We searched electronic reference databases through March 2005, studies that referenced Reaven's seminal article, abstracts presented at meetings in 2003 to 2004, and queried experts. Two reviewers independently assessed eligibility. Longitudinal studies reporting associations between MetSyn and cardiovascular events or mortality were eligible. Two reviewers independently used a standardized form to collect data from published reports. Authors were contacted. Study quality was assessed by the control of selection, detection, and attrition biases.
RESULTS: We found 37 eligible studies that included 43 cohorts (inception 1971 to 1997) and 172,573 individuals. Random effects meta-analyses showed MetSyn had a relative risk (RR) of cardiovascular events and death of 1.78 (95% confidence interval [CI] 1.58 to 2.00). The association was stronger in women (RR 2.63 vs. 1.98, p = 0.09), in studies enrolling lower risk (<10%) individuals (RR 1.96 vs. 1.43, p = 0.04), and in studies using factor analysis or the World Health Organization definition (RR 2.68 and 2.06 vs. 1.67 for National Cholesterol Education Program definition and 1.35 for other definitions; p = 0.005). The association remained after adjusting for traditional cardiovascular risk factors (RR 1.54, 95% CI 1.32 to 1.79).
CONCLUSIONS: The best available evidence suggests that people with MetSyn are at increased risk of cardiovascular events. These results can help clinicians counsel patients to consider lifestyle interventions, and should fuel research of other preventive interventions.

PMID 17258085  J Am Coll Cardiol. 2007 Jan 30;49(4):403-14. doi: 10.10・・・
著者: Célia Lloret Linares, Anne Laure Pelletier, Sébastien Czernichow, Anne Claire Vergnaud, Dominique Bonnefont-Rousselot, Philippe Levy, Philippe Ruszniewski, Eric Bruckert
雑誌名: Pancreas. 2008 Jul;37(1):13-2. doi: 10.1097/MPA.0b013e31816074a1.
Abstract/Text OBJECTIVES: The aim of this study was to assess retrospectively the prevalence and the predictive factors of acute pancreatitis (AP) in a population of patients referred in our endocrinology department for evaluation of very high triglyceride (TG) levels.
METHODS: One hundred twenty-nine patients (119 with type IV phenotypes and 10 with type V phenotypes according to Fredrickson's classification) were referred to our hospital between 2000 and 2005.
RESULTS: Twenty-six subjects (20.2% of the population) presented with AP. This population was significantly younger at diagnosis of hyperlipidemia (32 vs 40 years, P < 0.001) and at age of investigation (43 vs 48 years, P = 0.05) and had maximum TG levels greater than the population without AP (44.7 vs 24.5, P < 0.001). Subjects of the third tertile of TG levels had a 4.0-fold increased risk (95% confidence interval, 1.3-12.3) of AP compared with the first tertile. Severe pancreatitis (need for intensive care, C-reactive protein >150 mg/L, or Balthazar score >C) was observed in 71.5% of the patients.
CONCLUSIONS: Twenty percent of patients with severe hypertriglyceridemia experience at least 1 attack of AP. Pancreatitis seems to occur in young patients at higher levels of TG than previously thought (85% of patients >30 g/L) and is associated with a severe clinical course.

PMID 18580438  Pancreas. 2008 Jul;37(1):13-2. doi: 10.1097/MPA.0b013e3・・・
著者: M Hassan Murad, Ahmad Hazem, Fernando Coto-Yglesias, Svitlana Dzyubak, Shabnum Gupta, Irina Bancos, Melanie A Lane, Patricia J Erwin, Lars Berglund, Tarig Elraiyah, Victor M Montori
雑誌名: BMC Endocr Disord. 2012 Mar 31;12:2. doi: 10.1186/1472-6823-12-2. Epub 2012 Mar 31.
Abstract/Text BACKGROUND: Hypertriglyceridemia may be associated with important complications. The aim of this study is to estimate the magnitude of association and quality of supporting evidence linking hypertriglyceridemia to cardiovascular events and pancreatitis.
METHODS: We conducted a systematic review of multiple electronic bibliographic databases and subsequent meta-analysis using a random effects model. Studies eligible for this review followed patients longitudinally and evaluated quantitatively the association of fasting hypertriglyceridemia with the outcomes of interest. Reviewers working independently and in duplicate reviewed studies and extracted data.
RESULTS: 35 studies provided data sufficient for meta-analysis. The quality of these observational studies was moderate to low with fair level of multivariable adjustments and adequate exposure and outcome ascertainment. Fasting hypertriglyceridemia was significantly associated with cardiovascular death (odds ratios (OR) 1.80; 95% confidence interval (CI) 1.31-2.49), cardiovascular events (OR, 1.37; 95% CI, 1.23-1.53), myocardial infarction (OR, 1.31; 95% CI, 1.15-1.49), and pancreatitis (OR, 3.96; 95% CI, 1.27-12.34, in one study only). The association with all-cause mortality was not statistically significant.
CONCLUSIONS: The current evidence suggests that fasting hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis.Précis: hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis.

PMID 22463676  BMC Endocr Disord. 2012 Mar 31;12:2. doi: 10.1186/1472-・・・
著者: J E Hokanson, M A Austin
雑誌名: J Cardiovasc Risk. 1996 Apr;3(2):213-9.
Abstract/Text OBJECTIVES: Despite nearly 40 years of research, the role of plasma triglyceride as a risk factor for cardiovascular disease remains elusive. The objectives of the present study were to quantify the magnitude of the association between triglyceride and cardiovascular disease in the general population, and to determine whether this relationship is independent of high-density lipoprotein (HDL) cholesterol, using the semi-quantitative techniques of metaanalysis.
METHODS AND DESIGN: Seventeen studies were selected for the analysis based on published reports of population-based, prospective studies, including 46413 men and 10864 women. To insure comparability, only studies reporting the association between fasting triglyceride levels and incident cardiovascular endpoints were included. Using standard meta-analysis calculations, relative risks (RR) and 95% confidence intervals (CI) were calculated and standardized with respect to a 1 mmol/l increase in triglyceride. Multivariable-adjusted RRs were determined for the six studies in men and two studies in women that reported adjustments for HDL cholesterol.
RESULTS: For men and women, the univariate RRs for triglyceride were 1.32 (95% Cl 1.26-1.39) and 1.76 (95% Cl 1.50-2.07), respectively, indicating an approximately 30% increased risk in men and a 75% increase in women. Adjustment of HDL cholesterol and other risk factors attenuated these RRs to 1.14 (95% Cl 1.05-1.28) and 1.37 (95% Cl 1.13-1.66), respectively, which were still statistically significant values.
CONCLUSION: Based on combined data from prospective studies, triglyceride is a risk factor for cardiovascular disease for both men and women in the general population, independent of HDL cholesterol. These finding demonstrate the necessity for clinical trials to evaluate whether lowering plasma triglyceride decreases the risk of cardiovascular disease.

PMID 8836866  J Cardiovasc Risk. 1996 Apr;3(2):213-9.
著者: Michael Miller, Neil J Stone, Christie Ballantyne, Vera Bittner, Michael H Criqui, Henry N Ginsberg, Anne Carol Goldberg, William James Howard, Marc S Jacobson, Penny M Kris-Etherton, Terry A Lennie, Moshe Levi, Theodore Mazzone, Subramanian Pennathur, American Heart Association Clinical Lipidology, Thrombosis, and Prevention Committee of the Council on Nutrition, Physical Activity, and Metabolism, Council on Arteriosclerosis, Thrombosis and Vascular Biology, Council on Cardiovascular Nursing, Council on the Kidney in Cardiovascular Disease
雑誌名: Circulation. 2011 May 24;123(20):2292-333. doi: 10.1161/CIR.0b013e3182160726. Epub 2011 Apr 18.
Abstract/Text
PMID 21502576  Circulation. 2011 May 24;123(20):2292-333. doi: 10.1161・・・
著者: M R Fortson, S N Freedman, P D Webster
雑誌名: Am J Gastroenterol. 1995 Dec;90(12):2134-9.
Abstract/Text OBJECTIVE: This study addresses three questions: 1) What are the clinical presentations of pancreatitis secondary to hyperlipidemia? 2) What is the role of alcohol, diabetes, or known causes of hypertriglyceridemia? and 3) Does the course of pancreatitis secondary to hypertriglyceridemia differ from that of other etiologies?
METHODS: We reviewed patients between 1982 and 1994 with a diagnosis of pancreatitis (577.0) and hypertriglyceridemia (272.0). Four hospitals participated. Seventy patients had a clinical presentation consistent with pancreatitis, that is elevated amylase and lipase or evidence of pancreatitis by ultrasound or CT imaging and serum triglyceride levels greater than 500 mg/dl or lactescent serum. Clinical data were derived from hospital admissions.
RESULTS: Hypertriglyceridemia was the etiology in 1.3-3.8% of patients discharged with a diagnosis of pancreatitis. A history of diabetes mellitus was present in 72%, hypertriglyceridemia in 77%, alcohol use 23%, and gallstones in 7%. Lipemic serum was described on admission in 45%. Mean triglyceride levels were 4587 +/- 3616 ml/dl. Amylase was elevated two times normal in 54%, and lipase was elevated two times normal in 67%. CT scans were abnormal in 82%, with peripancreatic fluid in 34%, pseudocyst 37%, and necrosis in 15%. Abscess occurred in 13%, death in 6%.
CONCLUSION: Acute pancreatitis secondary to hyperlipidemia is characterized by three presentations. All patients present with abdominal pain, nausea, and vomiting of hours to days duration. The most common presentation is a poorly controlled diabetic with a history of hypertriglyceridemia. The second presentation is the alcoholic found to have hypertriglyceridemia or lactescent serum on admission. The third, about 15-20% of patients, is the nondiabetic, nonalcoholic, nonobese patient with drug- or diet-induced hypertriglyceridemia.

PMID 8540502  Am J Gastroenterol. 1995 Dec;90(12):2134-9.
著者: P P Toskes
雑誌名: Gastroenterol Clin North Am. 1990 Dec;19(4):783-91.
Abstract/Text Marked elevation of triglyceride levels appears to be causally linked to acute pancreatitis and is found in 12% to 38% of patients presenting with acute pancreatitis. Elevated cholesterol levels are not associated with pancreatitis. The pathogenesis of pancreatitis associated with hypertriglyceridemia is not clear. Clinical recognition of this association is extremely important, because therapy with diet and lipid-lowering agents may prevent development of pancreatitis.

PMID 2269517  Gastroenterol Clin North Am. 1990 Dec;19(4):783-91.
著者: Mitsuhiro Yokoyama, Hideki Origasa, Masunori Matsuzaki, Yuji Matsuzawa, Yasushi Saito, Yuichi Ishikawa, Shinichi Oikawa, Jun Sasaki, Hitoshi Hishida, Hiroshige Itakura, Toru Kita, Akira Kitabatake, Noriaki Nakaya, Toshiie Sakata, Kazuyuki Shimada, Kunio Shirato, Japan EPA lipid intervention study (JELIS) Investigators
雑誌名: Lancet. 2007 Mar 31;369(9567):1090-8. doi: 10.1016/S0140-6736(07)60527-3.
Abstract/Text BACKGROUND: Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease. We aimed to test the hypothesis that long-term use of eicosapentaenoic acid (EPA) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish.
METHODS: 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999. Patients were randomly assigned to receive either 1800 mg of EPA daily with statin (EPA group; n=9326) or statin only (controls; n=9319) with a 5-year follow-up. The primary endpoint was any major coronary event, including sudden cardiac death, fatal and non-fatal myocardial infarction, and other non-fatal events including unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting. Analysis was by intention-to-treat. The study was registered at ClinicalTrials.gov, number NCT00231738.
FINDINGS: At mean follow-up of 4.6 years, we detected the primary endpoint in 262 (2.8%) patients in the EPA group and 324 (3.5%) in controls-a 19% relative reduction in major coronary events (p=0.011). Post-treatment LDL cholesterol concentrations decreased 25%, from 4.7 mmol/L in both groups. Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events. Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group. Sudden cardiac death and coronary death did not differ between groups. In patients with a history of coronary artery disease who were given EPA treatment, major coronary events were reduced by 19% (secondary prevention subgroup: 158 [8.7%] in the EPA group vs 197 [10.7%] in the control group; p=0.048). In patients with no history of coronary artery disease, EPA treatment reduced major coronary events by 18%, but this finding was not significant (104 [1.4%] in the EPA group vs 127 [1.7%] in the control group; p=0.132).
INTERPRETATION: EPA is a promising treatment for prevention of major coronary events, and especially non-fatal coronary events, in Japanese hypercholesterolaemic patients.

PMID 17398308  Lancet. 2007 Mar 31;369(9567):1090-8. doi: 10.1016/S014・・・
著者: Allen J Taylor, Todd C Villines, Eric J Stanek, Patrick J Devine, Len Griffen, Michael Miller, Neil J Weissman, Mark Turco
雑誌名: N Engl J Med. 2009 Nov 26;361(22):2113-22. doi: 10.1056/NEJMoa0907569. Epub 2009 Nov 15.
Abstract/Text BACKGROUND: Treatment added to statin monotherapy to further modify the lipid profile may include combination therapy to either raise the high-density lipoprotein (HDL) cholesterol level or further lower the low-density lipoprotein (LDL) cholesterol level.
METHODS: We enrolled patients who had coronary heart disease or a coronary heart disease risk equivalent, who were receiving long-term statin therapy, and in whom an LDL cholesterol level under 100 mg per deciliter (2.6 mmol per liter) and an HDL cholesterol level under 50 mg per deciliter for men or 55 mg per deciliter for women (1.3 or 1.4 mmol per liter, respectively) had been achieved. The patients were randomly assigned to receive extended-release niacin (target dose, 2000 mg per day) or ezetimibe (10 mg per day). The primary end point was the between-group difference in the change from baseline in the mean common carotid intima-media thickness after 14 months. The trial was terminated early, on the basis of efficacy, according to a prespecified analysis conducted after 208 patients had completed the trial.
RESULTS: The mean HDL cholesterol level in the niacin group increased by 18.4% over the 14-month study period, to 50 mg per deciliter (P < 0.001), and the mean LDL cholesterol level in the ezetimibe group decreased by 19.2%, to 66 mg per deciliter (1.7 mmol per liter) (P < 0.001). Niacin therapy significantly reduced LDL cholesterol and triglyceride levels; ezetimibe reduced the HDL cholesterol and triglyceride levels. As compared with ezetimibe, niacin had greater efficacy regarding the change in mean carotid intima-media thickness over 14 months (P = 0.003), leading to significant reduction of both mean (P = 0.001) and maximal carotid intima-media thickness (P < or = 0.001 for all comparisons). Paradoxically, greater reductions in the LDL cholesterol level in association with ezetimibe were significantly associated with an increase in the carotid intima-media thickness (R = -0.31, P < 0.001). The incidence of major cardiovascular events was lower in the niacin group than in the ezetimibe group (1% vs. 5%, P = 0.04 by the chi-square test).
CONCLUSIONS: This comparative-effectiveness trial shows that the use of extended-release niacin causes a significant regression of carotid intima-media thickness when combined with a statin and that niacin is superior to ezetimibe. (ClinicalTrials.gov number, NCT00397657.)

2009 Massachusetts Medical Society
PMID 19915217  N Engl J Med. 2009 Nov 26;361(22):2113-22. doi: 10.1056・・・
著者: ACCORD Study Group, Henry N Ginsberg, Marshall B Elam, Laura C Lovato, John R Crouse, Lawrence A Leiter, Peter Linz, William T Friedewald, John B Buse, Hertzel C Gerstein, Jeffrey Probstfield, Richard H Grimm, Faramarz Ismail-Beigi, J Thomas Bigger, David C Goff, William C Cushman, Denise G Simons-Morton, Robert P Byington
雑誌名: N Engl J Med. 2010 Apr 29;362(17):1563-74. doi: 10.1056/NEJMoa1001282. Epub 2010 Mar 14.
Abstract/Text BACKGROUND: We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease.
METHODS: We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.
RESULTS: The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P=0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P=0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P=0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P=0.057 for interaction).
CONCLUSIONS: The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)

2010 Massachusetts Medical Society
PMID 20228404  N Engl J Med. 2010 Apr 29;362(17):1563-74. doi: 10.1056・・・
著者: J C LaRosa, J He, S Vupputuri
雑誌名: JAMA. 1999 Dec 22-29;282(24):2340-6.
Abstract/Text CONTEXT: Lowering low-density lipoprotein cholesterol (LDL-C) is known to reduce risk of recurrent coronary heart disease in middle-aged men. However, this effect has been uncertain in elderly people and women.
OBJECTIVE: To estimate the risk reduction of coronary heart disease and total mortality associated with statin drug treatment, particularly in elderly individuals and women.
DATA SOURCES: Trials published in English-language journals were retrieved by searching MEDLINE (1966-December 1998), bibliographies, and authors' reference files.
STUDY SELECTION: Studies in which participants were randomized to statin or control treatment for at least 4 years and clinical disease or death was the primary outcome were included in the meta-analysis (5 of 182 initially identified).
DATA EXTRACTION: Information on sample size, study drug duration, type and dosage of statin drug, participant characteristics at baseline, reduction in lipids during intervention, and outcomes was abstracted independently by 2 authors (J.H. and S.V.) using a standardized protocol. Disagreements were resolved by consensus.
DATA SYNTHESIS: Data from the 5 trials, with 30 817 participants, were included in this meta-analysis. The mean duration of treatment was 5.4 years. Stati n drug treatment was associated with a20% reduction in total cholesterol, 28% reduction in LDL-C, 13% reduction in triglycerides, and 5% increase in high-density lipoprotein cholesterol. Overall, statin drug treatment reduced risk 31 % in major coronary events (95% confidence interval [CI], 26%-36%) and 21 % in all-cause mortality (95% CI, 14%-28%). The risk reduction in major coronary events was similar between women (29%; 95% Cl, 13 %-42 %) and men (31 %; 95% CI, 26%-35%), and between persons aged at least 65 years (32%; 95% CI, 23%-39%) and persons younger than 65 years (31 %; 95% CI, 24%-36%).
CONCLUSIONS: Our meta-analysis indicates that reduction in LDL-C associated with statin drug treatment decreases the risk of coronary heart disease and all-cause mortality. The risk reduction was similar for men and women and for elderly and middle-aged persons.

PMID 10612322  JAMA. 1999 Dec 22-29;282(24):2340-6.
著者: A Keech, R J Simes, P Barter, J Best, R Scott, M R Taskinen, P Forder, A Pillai, T Davis, P Glasziou, P Drury, Y A Kesäniemi, D Sullivan, D Hunt, P Colman, M d'Emden, M Whiting, C Ehnholm, M Laakso, FIELD study investigators
雑誌名: Lancet. 2005 Nov 26;366(9500):1849-61. doi: 10.1016/S0140-6736(05)67667-2.
Abstract/Text BACKGROUND: Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease, partly owing to dyslipidaemia, which can be amenable to fibrate therapy. We designed the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study to assess the effect of fenofibrate on cardiovascular disease events in these patients.
METHODS: We did a multinational, randomised controlled trial with 9795 participants aged 50-75 years, with type 2 diabetes mellitus, and not taking statin therapy at study entry. After a placebo and a fenofibrate run-in phase, we randomly assigned patients (2131 with previous cardiovascular disease and 7664 without) with a total-cholesterol concentration of 3.0-6.5 mmol/L and a total-cholesterol/HDL-cholesterol ratio of 4.0 or more or plasma triglyceride of 1.0-5.0 mmol/L to micronised fenofibrate 200 mg daily (n=4895) or matching placebo (n=4900). Our primary outcome was coronary events (coronary heart disease death or non-fatal myocardial infarction); the outcome for prespecified subgroup analyses was total cardiovascular events (the composite of cardiovascular death, myocardial infarction, stroke, and coronary and carotid revascularisation). Analysis was by intention to treat. The study was prospectively registered (number ISRCTN 64783481).
FINDINGS: Vital status was confirmed on all but 22 patients. Averaged over the 5 years' study duration, similar proportions in each group discontinued study medication (10% placebo vs 11% fenofibrate) and more patients allocated placebo (17%) than fenofibrate (8%; p<0.0001) commenced other lipid treatments, predominantly statins. 5.9% (n=288) of patients on placebo and 5.2% (n=256) of those on fenofibrate had a coronary event (relative reduction of 11%; hazard ratio [HR] 0.89, 95% CI 0.75-1.05; p=0.16). This finding corresponds to a significant 24% reduction in non-fatal myocardial infarction (0.76, 0.62-0.94; p=0.010) and a non-significant increase in coronary heart disease mortality (1.19, 0.90-1.57; p=0.22). Total cardiovascular disease events were significantly reduced from 13.9% to 12.5% (0.89, 0.80-0.99; p=0.035). This finding included a 21% reduction in coronary revascularisation (0.79, 0.68-0.93; p=0.003). Total mortality was 6.6% in the placebo group and 7.3% in the fenofibrate group (p=0.18). Fenofibrate was associated with less albuminuria progression (p=0.002), and less retinopathy needing laser treatment (5.2%vs 3.6%, p=0.0003). There was a slight increase in pancreatitis (0.5%vs 0.8%, p=0.031) and pulmonary embolism (0.7%vs 1.1%, p=0.022), but no other significant adverse effects.
INTERPRETATION: Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events. It did reduce total cardiovascular events, mainly due to fewer non-fatal myocardial infarctions and revascularisations. The higher rate of starting statin therapy in patients allocated placebo might have masked a moderately larger treatment benefit.

PMID 16310551  Lancet. 2005 Nov 26;366(9500):1849-61. doi: 10.1016/S01・・・
著者: National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
雑誌名: Circulation. 2002 Dec 17;106(25):3143-421.
Abstract/Text
PMID 12485966  Circulation. 2002 Dec 17;106(25):3143-421.
著者: Yasushi Saito, Mitsuhiro Yokoyama, Hideki Origasa, Masunori Matsuzaki, Yuji Matsuzawa, Yuichi Ishikawa, Shinichi Oikawa, Jun Sasaki, Hitoshi Hishida, Hiroshige Itakura, Toru Kita, Akira Kitabatake, Noriaki Nakaya, Toshiie Sakata, Kazuyuki Shimada, Kunio Shirato, JELIS Investigators, Japan
雑誌名: Atherosclerosis. 2008 Sep;200(1):135-40. doi: 10.1016/j.atherosclerosis.2008.06.003. Epub 2008 Jun 19.
Abstract/Text BACKGROUND: Japan EPA Lipid Intervention Study (JELIS) was a large-scale clinical trial examining the effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD) in hypercholesterolemic patients. Herein, we focused on risk factors other than low-density lipoprotein cholesterol (LDL-C) to investigate the effects of EPA on CAD among JELIS primary prevention cases.
METHODS: Hypercholesterolemic patients on statin therapy but without evidence of CAD (n=14,981) were randomly assigned to an EPA group (n=7503) or a control group (n=7478). The relationships between incident CAD, the number of CAD risk factors (hypercholesterolemia; obesity; high triglyceride (TG) or low high-density lipoprotein cholesterol (HDL-C); diabetes; and hypertension) and EPA treatment were investigated.
RESULTS: For the control and EPA groups combined, a higher number of risk factors was directly associated with an increased incidence of CAD. Incidence was lower for the EPA group than for the control group regardless of the numbers of risk factors. Compared to patients with normal serum TG and HDL-C levels, those with abnormal levels (TG >or=150 mg/dL; HDL-C <40 mg/dL) had significantly higher CAD hazard ratio (HR: 1.71; 95% CI: 1.11-2.64; P=0.014). In this higher risk group, EPA treatment suppressed the risk of CAD by 53% (HR: 0.47; 95% CI: 0.23-0.98; P=0.043).
CONCLUSIONS: Multiple risk factors besides cholesterol are associated with markedly increased incidence of CAD. High TG with low HDL-C represents a particularly potent risk factor. EPA was effective in reducing the incidence of CAD events for patients with this dyslipidemic pattern, suggesting that EPA may be especially beneficial in patients who with abnormal TG and HDL-C levels.

PMID 18667204  Atherosclerosis. 2008 Sep;200(1):135-40. doi: 10.1016/j・・・

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