Three Reasons to Abandon Low-Density Lipoprotein Targets

Name: Work Video:
Duration: 3 min 30 s
Rodney A. Hayward; Harlan M. Krumholz
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225, 2599], 'CT': [141, 226, 2600], '(H.M.K.).': [142, 227], 'KrumholzHarlan': [146], 'Krumholz': [148, 2505, 2528, 2643, 2659, 2730, 3095, 4002, 4056, 4166], 'Originally': [228], 'published1': [229], 'Jan': [230], '2012https://doi.org/10.1161/CIRCOUTCOMES.111.964676Circulation:': [231], 'Outcomes.': [235, 2655, 2670, 2779, 2850, 3054], '2012;5:2–5The': [236], 'updated': [237, 2863], 'clinical': [238, 346, 401, 412, 482, 552, 643, 658, 734, 742, 1028, 1284, 1405, 1416, 2214, 2352, 2364, 3147], 'guidelines': [239, 277, 448, 576, 1552, 1707, 2120, 2614, 3949], 'cholesterol': [241, 339, 367, 860, 2617, 2923, 3031, 3112, 3301, 3955], 'testing': [242], 'management': [244, 3729, 3987], '(Adult': [245], '(ATP)': [248], 'IV)': [249], 'from': [250, 399, 563, 1321, 2318, 2333, 2520, 2539, 2971, 3259, 3961], 'Expert': [252], 'on': [254, 498, 733, 945, 1122, 1283, 1335, 1361, 1394, 1507, 2001, 2021, 2035, 2062, 2165, 2194, 2212, 2349, 3101, 3600, 4133], 'Detection,': [255], 'High': [260], 'Blood': [261, 288, 2526, 2609, 3183, 3883], 'Cholesterol': [262, 3152, 3572, 4103], 'in': [263, 273, 391, 410, 511, 518, 577, 623, 669, 687, 691, 905, 980, 1003, 1099, 1193, 1197, 1201, 1237, 1241, 1245, 1288, 1456, 1663, 1779, 1818, 1888, 1950, 1959, 2007, 2016, 2112, 2131, 2143, 2158, 2226, 2276, 2464, 2558, 2615, 2646, 2790, 2927, 2974, 3043, 3068, 3087, 3173, 3190, 3237, 3561, 3682, 3730, 3808, 3984, 4027], 'Adults': [264], 'are': [265, 278, 389, 457, 508, 554, 581, 788, 958, 1000, 1038, 1348, 1553, 1621, 1806, 1825, 1842, 2313, 2427, 2561], 'under': [266, 2087], 'development': [267], 'due': [269], 'be': [271, 707, 893, 1049, 1059, 1114, 1527, 1538, 1566, 1631, 1677, 1733, 1794, 1855, 1921, 1991, 2084, 2663, 3081], 'published': [272, 1706], '2012.': [274], 'These': [275, 1823], 'influential': [276], 'organized': [279], 'funded': [281], 'by': [282, 583, 608, 820, 845, 926, 1116, 1296, 1670, 1747, 2430, 2466, 2483, 2508], 'Heart,': [285, 2523, 2606, 3180], 'Lung,': [286, 2524, 2607, 3181], 'Institute': [289], '(NHLBI)': [290], 'carry': [292], 'imprimatur': [294], 'federal': [297], 'government.': [298], 'In': [299, 427, 673, 764, 948, 1603, 1941, 2248], 'this': [300, 689, 747, 1604, 1696, 1728, 1765, 2559], 'iteration,': [301], 'NHLBI': [303], 'has': [304, 646, 744, 1055, 1331, 1391, 1460, 1771, 2378], 'a': [305, 329, 376, 472, 538, 564, 567, 572, 584, 620, 776, 884, 894, 967, 1043, 1095, 1117, 1315, 1332, 1343, 1362, 1372, 1381, 1408, 1454, 1491, 1496, 1504, 1579, 1588, 1632, 1639, 1681, 1690, 1751, 1821, 1885, 1922, 1929, 2029, 2045, 2068, 2153, 2166, 2200, 2224, 2236, 2277, 2284, 2319, 2376, 2441, 2536, 2549, 2719, 2770, 2867, 2931, 3606, 3639, 3957], 'stated': [306, 343, 390], 'goal': [307], 'integrating': [309], 'its': [310], 'set': [311, 2440], 'Risk': [314, 1141, 1167, 1208, 2898, 2910, 3189, 3802], 'Reduction': [315, 1142], 'guidelines.1A': [316], 'primary': [317, 370, 379, 616, 2742, 3088], 'focus': [318], 'previous': [321], 'version': [322], 'guidelines,': [325, 521, 2008], 'ATP': [326, 341, 360, 437, 454, 478, 628, 2056, 2354], 'III,': [327], 'was': [328, 407, 693, 1302, 2178, 2219, 2295, 2346, 2462], 'strategy': [330], 'treating': [332, 467, 651, 728, 1661], 'patients': [333, 468, 652, 1577, 1726, 2311, 2805, 3238, 3731], 'target': [335, 371, 730, 3084], 'low-density': [336, 1248, 2715, 2833, 3029], 'lipoprotein': [337, 914, 2716, 2834, 2837, 3030], '(LDL)': [338], 'levels.': [340, 947], 'III': [342, 361, 2057, 3158], 'that': [344, 350, 406, 428, 440, 474, 534, 540, 569, 618, 665, 714, 717, 727, 740, 753, 757, 787, 829, 864, 873, 883, 923, 956, 962, 1031, 1051, 1091, 1111, 1375, 1440, 1446, 1484, 1560, 1672, 1725, 1745, 1798, 1834, 1848, 1858, 1915, 1947, 1963, 1973, 2070, 2089, 2118, 2243, 2273, 2299, 2305, 2412, 2426, 2530], '"recent': [345], 'trials': [347, 659, 710, 751, 1029, 2977, 3148, 3760], 'robustly': [348], 'show': [349, 752], 'LDL-lowering': [351, 1919], 'therapy': [352, 382, 1037, 1949, 1978, 2102, 2130, 3086, 3264, 3679], 'reduces': [353, 993], 'risk': [354, 683, 692, 1016, 1074, 1104, 1112, 1317, 1337, 1346, 1366, 1437, 1494, 1499, 1581, 1669, 1730, 1758, 2173, 2368, 2370, 2612, 2634, 2797, 2865, 2894, 3241, 3675], 'CHD.': [356], 'For': [357, 2394], 'these': [358, 676, 996, 1006, 1591, 1852, 2011], 'reasons,': [359], 'continues': [362], 'identify': [364, 2310], 'elevated': [365, 1686, 1713, 3033], 'LDL': [366, 470, 638, 655, 946, 998, 1009, 1092, 1124, 1177, 1220, 1307, 1313, 1469, 1485, 1544, 1550, 1662, 1687, 1714, 1804, 2022, 2058, 2095, 2104, 2135, 2147, 2176, 2246, 2306, 3908], 'as': [368, 514, 592, 703, 792, 804, 815, 888, 903, 911, 1841, 2094, 2281, 2283, 2842], 'cholesterol-lowering': [373, 2965], 'therapy.': [374, 3104], 'As': [375, 1459], 'result,': [377], 'goals': [380, 1956, 1968], 'cutpoints': [385], 'initiating': [387], 'treatment': [388, 579, 587, 836, 943, 968, 984, 992, 1427, 1455, 1477, 1511, 1643, 1737, 1749, 1770, 1792, 1903, 2142, 2156, 2161, 2206, 2286, 2391, 2717, 2740, 3277, 3952], 'terms': [392], 'LDL."': [394], 'This': [395, 2115, 2294], 'reasoning,': [396], 'however,': [397], 'diverged': [398], 'evidence,': [402, 546, 2067, 2398], 'recommending': [403, 2127, 2140], 'an': [404, 432, 821, 970, 1060, 1123, 1322, 1326, 2033, 2262, 2334, 2435, 2453, 3045, 3071], 'approach': [405, 588, 1383, 1570, 2279], 'not': [408, 694, 712, 754, 835, 855, 1001, 1039, 1068, 1082, 1094, 1303, 1350, 1379, 1419, 1466, 1487, 1530, 1537, 1562, 1648, 1676, 1772, 1800, 1862, 1896, 2025, 2072, 2111, 2126, 2220, 2296, 2308, 2347, 2416, 2428, 2568], 'tested': [409, 647, 660, 746], 'any': [411, 927, 2269, 3115], 'trial.Outcomes': [413], 'research': [414, 2116, 2537], 'promotes': [415], 'need': [417, 493, 856], 'demonstrate': [419, 713, 1030, 1884, 2223], 'benefit': [420, 773, 850, 965, 1341, 1370, 1589, 1679, 1743, 2317, 2793], 'before': [421, 2004], 'making': [422], 'recommendations': [423, 1574, 2012, 2361, 2425], 'medical': [425], 'intervention.2,3': [426], 'spirit,': [429], 'we': [430, 612, 920, 1515, 2399], 'present': [431, 613], 'open': [433], 'letter': [434], 'Committee': [439, 2438], 'provides': [441, 1503], 'rationale': [443, 1924], 'why': [445], 'new': [447, 573], 'should': [449, 1048, 1920, 2662], 'abandon': [450, 463], 'treat-to-target': [452, 2201, 2228, 2278, 2323], 'paradigm.Dear': [453], 'Committee,We': [456], 'writing': [458], 'encourage': [460, 2040], 'you': [461], 'paradigm': [465, 2324], 'targets,': [471], 'change': [473, 495, 622, 2377], 'will': [475, 929, 1113, 2121, 2439, 2451], 'better': [476], 'align': [477, 2360], 'with': [480, 1021, 1305, 1578, 1665, 1685, 1702, 1781, 1820, 2362, 2372, 2392, 2396, 2806, 2925, 3014, 3027, 3732, 4109], 'current': [481, 2113, 3986], 'evidence.': [483, 500, 2216, 2353, 2432], 'Changing': [484], 'long-held': [485], 'beliefs': [486, 507], 'is': [487, 496, 502, 530, 533, 731, 774, 780, 851, 880, 952, 1067, 1081, 1087, 1093, 1102, 1314, 1418, 1470, 1483, 1587, 1594, 1647, 1697, 1738, 1759, 1799, 1839, 1881, 1894, 2024, 2110, 2163, 2208, 2506, 2532, 2546], 'never': [488], 'easy,': [489], 'even': [490, 897, 1606, 2086, 2240], 'when': [491, 505, 2010, 2250], 'based': [497, 732, 2061, 2164, 2209, 2348], 'strong': [499, 1088, 2030, 2363, 2424], 'Change': [501], 'especially': [503, 1019, 2009], 'difficult': [504], 'prior': [506], 'firmly': [509], 'embedded': [510], 'culture,': [512], 'accepted': [513], 'dogma,': [515], 'codified': [517], 'books,': [519], 'articles,': [520], 'public': [522], 'service': [523, 2455], 'announcements,': [524], 'performance': [526, 3281], 'measures.': [527, 3282], 'Still,': [528], 'what': [529], 'most': [531, 2255], 'important': [532, 900], 'guideline': [535, 2618, 2623, 2628], 'committees': [536], 'follow': [537, 2449], 'process': [539], 'adheres': [541], 'closely': [542], 'scientific': [545, 1089, 1421, 2271, 2551], 'particularly': [547], 'details': [549], 'trials—which': [553], 'abundant': [555], 'lipid': [557, 667, 719, 759, 1930, 2253, 3102], 'treatment.The': [558], 'evidence': [559, 736, 770, 827, 937, 1080, 1090, 1377, 1422, 1833, 1880, 1898, 1916, 2302, 2365, 2414, 2712], 'supports': [560], 'moving': [561], 'away': [562], 'target-based': [565, 1382, 1551, 1569], 'approach,': [566, 2092, 2157, 2239, 2264, 2287, 2436], 'step': [568], 'could': [570, 868, 2229], 'launch': [571], 'era': [574, 2648], 'which': [578, 597, 846, 990, 1289, 1508, 2159, 2227], 'targets': [580, 1805, 2036, 2059, 3278], 'replaced': [582], 'more': [585, 1827, 2185, 2210, 2237, 2314, 2664], 'tailored': [586, 2155, 2205, 2238, 2285], '(sometimes': [589], 'referred': [590, 790], '"individualized"': [593], 'or': [594, 908, 978, 994, 1023, 1108, 1271, 1309, 1426, 1495, 1535, 2137, 2233, 2585, 3305, 3680], '"personalized"': [595], 'care),': [596], 'can': [598, 839, 1571, 1609, 1614, 1957, 1969, 1979, 2037, 3078], 'improve': [599, 758, 930, 2891], 'patient': [600, 671, 722, 762, 772, 931, 1436, 1961, 2002, 2367], 'outcomes': [601, 2003, 2650], 'while': [602, 2190], 'reducing': [603, 2694], 'harms': [604, 1905], 'costs': [606], 'caused': [607], 'overtreating': [609, 2138], 'low-risk/low-benefit': [610], 'individuals.4–8Below,': [611], 'briefly': [614], 'reasons': [617, 940], 'justify': [619, 1660], 'major': [621, 641, 1356], 'next': [625], 'generation': [626, 800], 'guidelines.There': [629], 'Is': [630, 1178, 1221, 2044], 'No': [631, 1188], 'Scientific': [632, 3609, 3686], 'Basis': [633], 'Support': [635], 'Treating': [636, 1542], 'TargetsFirst,': [639], 'no': [640, 741], 'randomized': [642, 3758], 'trial': [644, 735, 743, 769, 826, 1285, 2215], '(RCT)': [645], 'benefits': [649, 1452, 1478, 1778, 2765], 'according': [653], 'targets.5': [656], 'The': [657, 709, 1008, 1411, 1568, 1846, 3754, 3812, 4005, 4100], 'fixed': [661], 'doses': [662, 796, 2196], 'drugs': [664, 678, 716, 756, 867, 3113], 'lower': [666, 1782], 'levels': [668, 720, 999, 1715, 2023, 3636], 'specific': [670], 'populations.': [672], 'some': [674], 'trials,': [677], 'were': [679, 1785, 2060, 2265, 2289], 'shown': [680, 1564, 1629, 1739, 1851, 1865], 'reduce': [682, 718, 721, 761, 807, 817, 840, 1441, 1836], '(eg,': [684, 696], 'statins),': [685], 'but': [686, 1401, 1429, 1797, 2032], 'others,': [688], 'reduction': [690, 1075, 1500, 1887, 2371, 2384, 2613, 2635], 'demonstrated': [695, 1057, 1462, 1946, 2117], 'clofibrate': [697], 'torcetrapib).': [699], 'Other': [700, 1165], 'drugs,': [701], 'such': [702, 803, 814, 887, 2093, 2434], 'ezetimibe,': [704], 'remain': [705], 'tested.': [708, 2075], 'do': [711, 2292, 2567, 3114], 'all': [715, 755, 767, 1710, 2445], 'risk.': [723, 763, 841, 2846], 'Thus,': [724, 824, 919, 1085], 'dogma': [726], 'belies': [737], 'fact': [739], 'yet': [745, 1649, 1773, 1863], 'strategy.As': [748], 'noted': [749, 1050], 'above,': [750, 2054], 'profiles': [760], 'fact,': [765, 2249], 'almost': [766], 'single': [777, 895, 1316], 'medication': [778, 1931], 'class—statins—that': [779], 'known': [781, 1650], 'have': [783, 870, 1355, 1561, 1615, 1627, 1655, 1689, 1741, 1850, 1860, 1945], 'multiple': [784], 'biological': [785, 1473], 'activities': [786], 'often': [789, 1358, 1817, 1826, 2013], '"pleiotropic"': [793], 'effects.': [794], 'Standard': [795], 'first': [799, 3018, 3640], 'statins,': [802, 813, 833, 1077, 1514], 'simvastatin,': [805], 'dramatically': [806], 'cardiovascular': [808, 1015, 1064, 1106, 1261, 1398, 1493, 1583, 1668, 1693, 1757, 1837, 1869, 2133, 2145, 2172, 2633, 2796, 2845, 2893, 3019, 3171, 3649], 'events': [809, 819, 1295, 1838, 1870, 3020], 'mortality.': [811, 1912], 'High-potency': [812], 'atorvastatin,': [816], 'nonfatal': [818], 'additional': [822], '15–20%.': [823], 'indicates': [828, 1247], 'use': [831, 1718, 1812, 1927], 'target,': [838], 'Although': [842, 1612], 'mechanism(s)': [844], 'statins': [847, 1613, 1720, 2198, 3042, 3599], 'exert': [848], 'their': [849, 875, 1352, 1995, 2041, 3765], 'controversial,': [852], 'one': [853], 'does': [854, 1378, 1465, 1486, 2307, 2415], 'impugn': [858], 'hypothesis': [861], 'recognize': [863, 955], 'different': [865, 1409, 3596], 'lipid-lowering': [866, 1653, 1815, 2373], 'possibly': [869], 'deleterious': [871], 'effects': [872, 1034, 1354, 1360, 1618], 'offset': [874], 'potential': [876, 1729, 2380, 2689], 'benefit.': [877], 'Further,': [878, 1913, 2203], 'it': [879, 951, 1066, 1320, 1464, 1593, 2109, 2218], 'quite': [881], 'possible': [882, 1717, 2221], 'surrogate': [885], 'measure,': [886], 'LDL,': [889, 925], 'may': [890, 917, 1384, 1534, 1536], 'appear': [891], 'entity': [896], 'though': [898], 'clinically': [899], 'subcomponents': [901], '(such': [902, 910], 'heterogeneity': [904], 'particle': [906], 'size)': [907], 'interactions': [909], 'total': [912, 1024], 'cholesterol/high-density': [913], '[HDL]': [915], 'ratio)': [916], 'exist.': [918], 'cannot': [921], 'assume': [922], 'lowering': [924, 2924, 3103], 'means,': [928], 'outcomes.A': [932], 'closer': [933], 'look': [934], 'at': [935, 1103, 1721, 1760, 2517, 3239], 'demonstrates': [938], 'further': [939], 'against': [941], 'basing': [942], 'decisions': [944, 2410], 'considering': [949], 'recommendations,': [950], 'useful': [953, 1002, 1097], 'there': [957, 1086, 1586, 1620, 1674, 1893], 'only': [959, 1330, 1598, 1732], '2': [960, 1444], 'factors': [961, 1347, 1439], 'determine': [963, 1448, 1900], 'individual': [971, 1457], 'patient:': [972], '(1)': [973], 'risks': [975, 1450, 1608, 1784], 'morbidity': [977, 1889, 1910], 'mortality': [979], 'absence': [982], '(2)': [986], 'degree': [988], 'increases': [995], 'risks.6': [997], 'either': [1004, 2122], 'areas.': [1007], 'level': [1010, 1308, 1329], 'contributes': [1011], 'little': [1012], 'estimating': [1014], 'overall': [1017, 1310, 1364, 1753, 2168], 'compared': [1020], 'non-HDL9': [1022], 'cholesterol/HDL': [1025], 'ratio.10–12': [1026], 'Moreover,': [1027], 'relative': [1033, 1073, 1300, 1498], 'statin': [1036, 1118, 1830, 2101, 2129, 2141, 2160, 2739, 3085], 'substantially': [1040, 1867, 1908], 'related': [1041, 1070, 1273], "patient's": [1044, 1363, 1492], 'pretreatment': [1045, 1306], 'LDL.13,14': [1046], 'It': [1047, 2329], 'although': [1052, 1078, 1673], 'C-reactive': [1053, 1258, 2886, 3035, 3079], 'protein': [1054, 2887, 3080], 'been': [1056, 1392, 1461, 1563, 1628, 1774, 1864, 2073], 'independent': [1061], 'predictor': [1062], 'risk,': [1065, 1442], 'strongly': [1069, 2244], 'entirely': [1083], 'consistent.13,15,16': [1084], 'very': [1096], 'factor': [1098, 2798], 'determining': [1100], 'who': [1101, 2312], 'disease': [1107, 1399, 1424], 'how': [1109, 2406], 'much': [1110], 'reduced': [1115], '(Table).Table.': [1119], 'Why': [1120], 'Focusing': [1121], 'Leads': [1126], 'Poor': [1128], 'Identification': [1129], 'Which': [1131], 'Patients': [1132, 4108], 'Benefit': [1133, 1146, 1169, 1213], 'Statin': [1135, 1172, 1215], 'Therapy*Baseline': [1136], '5-Year': [1137], 'CV': [1138, 1140, 1160, 1166, 1207, 1294, 1311, 1336, 1365], 'RiskAbsolute': [1139], '5': [1144, 1150], 'YearsNet': [1145], 'If': [1147, 1585, 1776, 1877], 'Treated': [1148], 'Years': [1151], 'With': [1152, 1205, 2433], '40': [1153, 1290], 'mg': [1154, 1291], 'Simvastatin': [1155], '(NNT': [1156], 'Prevent': [1158], '1': [1159, 2593], 'Event)A.': [1161], 'Do': [1162, 1203, 3111], 'Those': [1163, 1204], 'Without': [1164], 'Factors': [1168, 1209, 3803], 'Considerably': [1170], 'Just': [1174, 1217], 'Because': [1175, 1218, 1345], 'Their': [1176, 1219, 2019], 'High?†': [1179], 'Male,': [1180, 1224], 'Age': [1181, 1225], '55': [1182, 1226], 'Years,': [1183, 1227], 'Nonsmoker,': [1184], 'SBP=120,': [1185], 'HDL=55,': [1186], 'CRP=5,': [1187, 1231], 'Family': [1189, 1233], 'History': [1190, 1234], 'LDL=90': [1191, 1243], 'mg/dL∼2%8': [1192], '1000125': [1194], 'LDL=145': [1195, 1239], 'mg/dL∼2.5%10': [1196], '1000100': [1198], 'LDL=190': [1199, 1235], 'mg/dL∼3%12': [1200], '100083B.': [1202], 'Many': [1206], 'Get': [1210], 'Much': [1211], 'Less': [1212], 'Naturally': [1222], 'Low?†': [1223], 'Smoker,': [1228], 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'mechanism': [1474, 2099, 2337], 'mediating': [1475], 'statins.': [1480, 2393, 2979], 'What': [1481], 'matters': [1482], 'appreciably': [1488], 'predict': [1490], "statin's": [1497], 'therefore': [1502], 'poor': [1505], 'premise': [1506], 'base': [1510], 'recommendations.': [1512], 'Beyond': [1513, 3910], 'must': [1516, 1990, 2400], 'extend': [1517], 'our': [1518], 'concern': [1519], 'question': [1522], 'treatments': [1525, 1559, 1824, 1853], 'might': [1526, 1675, 1793], 'harmful': [1528], 'just': [1531, 1861], 'they': [1533, 1626, 1835, 1859], 'effective.The': [1539], 'Safety': [1540], 'Has': [1546], 'Never': [1547], 'Been': [1548], 'ProvenThe': [1549], 'commonly': [1554, 1807], 'used': [1555, 1808, 3082], 'indirectly': [1557], 'promote': [1558, 1708, 1810, 2389], 'safe.17': [1567], 'lead': [1572], 'treat': [1576, 3013], 'outcomes.': [1584], 'patients,': [1592, 1906, 3685], 'likely': [1595, 2315], 'accrue': [1597], 'after': [1599, 3638], 'decades': [1600], 'treatment.': [1602], 'setting,': [1605], 'minor': [1607], 'outweigh': [1610], 'benefits.': [1611], 'appreciable': [1616, 1678], 'side': [1617], 'potentially': [1622], 'serious': [1623], 'drug-drug': [1624], 'interactions,': [1625], 'relatively': [1633], 'safe': [1634, 1856], 'class': [1635], 'medications': [1637, 1989], 'over': [1638, 1680], '5-': [1640, 1754, 2169], '7-year': [1642], 'period.': [1644], 'Longer-term': [1645], 'safety': [1646, 1657, 1844, 2963], 'other': [1652], 'agents': [1654], 'less': [1656, 1795, 2397], 'data.Some': [1658], 'advocates18,19': [1659], 'individuals': [1664, 1684], '10-year': [1667, 1682, 1756, 2171], 'noting': [1671], 'period,': [1683], 'generally': [1688], '"life-time"': [1692], 'risk;': [1694], 'incidentally,': [1695], 'also': [1698, 1895], 'true': [1699, 3306], 'LDL.': [1704], 'Recently': [1705], 'screening': [1709, 3169], 'children': [1711], 'early': [1722, 1736, 1769], 'ages.20': [1723], 'Recommending': [1724], 'take': [1727], 'would': [1731, 2274], 'justified': [1734], 'if': [1735], 'substantial': [1742, 1886, 1960], 'beyond': [1744], 'achieved': [1746, 3637], 'delaying': [1748], 'until': [1750], "person's": [1752, 2167], 'least': [1761], 'moderately': [1762], 'elevated.': [1763], 'However,': [1764, 2217], 'beneficial': [1766], 'demonstrated.': [1775], 'long-term': [1777], 'populations': [1780], 'short-term': [1783], 'secure': [1786], 'substantial,': [1788], 'then': [1789, 1892], 'uncertainty': [1790], 'about': [1791, 2182], 'troublesome,': [1796], 'case.In': [1802], 'addition,': [1803], 'newer': [1814], 'treatments,': [1816], 'combination': [1819], 'expensive': [1828], 'than': [1829, 2199], 'treatment,': [1831], 'lacking,': [1840], 'adequate': [1843, 2128, 2413], 'data.17': [1845], 'suggestion': [1847], 'RCTs': [1849, 1944], 'decrease': [1868], 'neglects': [1871], 'symmetry': [1873], 'statistical': [1875], 'power.': [1876], 'RCT': [1879, 2066, 2301], 'insufficient': [1882], 'mortality,': [1891], 'enough': [1897], 'seriously': [1904], 'including': [1907], 'increasing': [1909, 2691], 'arguing': [1914], 'significant': [1918], 'sufficient': [1923, 2026], 'promoting': [1926], 'ignores': [1932], 'recent': [1933, 1942, 3146], 'examples': [1934], 'dangers': [1937], 'trusting': [1939], 'surrogates.': [1940], 'years,': [1943], 'intensive': [1948], 'pursuit': [1951], 'recommended': [1953, 1966, 2006, 2714], 'pressure': [1955], 'result': [1958, 2275], 'harm,21': [1962], 'striving': [1964], 'glycemic': [1967], 'increase': [1970], 'mortality,21': [1971], 'torcetrapib': [1974, 3236], 'hormone': [1976, 3263], 'replacement': [1977, 3678], 'both': [1980, 1997], '"improve': [1981], 'lipids"': [1982], 'elevate': [1984], 'risk.22,23': [1985], 'classes': [1987], 'adequately': [1992], 'evaluated': [1993], 'effects,': [1996], 'positive': [1998], 'negative,': [2000], 'being': [2005, 2096, 2105, 2280], 'become': [2014], 'mandated': [2015], 'quality': [2017, 2692], 'measures.24': [2018], 'justification': [2027], 'recommendation,': [2031], 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[2552], 'board': [2553], 'UnitedHealth.FootnotesThe': [2555], 'opinions': [2556, 2572], 'expressed': [2557], 'article': [2560], 'authors': [2565], 'necessarily': [2569], 'represent': [2570], 'American': [2575, 3943, 4039, 4079], 'Heart': [2576, 2919, 3947, 3963], 'Association,': [2577], 'Michigan,': [2584], 'University.Correspondence': [2587], 'SM,': [2592, 3127, 3209], 'Church': [2594], 'St,': [2595], 'Suite': [2596], '200,': [2597], '06510.': [2601], 'E-mail': [2602], 'harlan.[email': [2603], 'protected]eduReferences1.': [2604], 'Institute.': [2610, 3184], 'adults:': [2616], 'update': [2619, 2624, 2629], '(ATP': [2620], 'IV);': [2621], 'hypertension': [2622], '(JNC': [2625], '8);': [2626], 'obesity': [2627], '(Obesity': [2630], '2);': [2631], 'integrated': [2632], 'guideline.': [2636], 'http://www.nhlbi.nih.gov/guidelines/cvd_adult/background.htm.': [2637], 'Accessed': [2638, 2913, 3121, 3197, 3269], 'December': [2639, 2914, 3122, 3198, 3270], '12,': [2640, 2915, 3123, 3199, 3271, 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