Plasma Concentration of C-Reactive Protein and Risk of Ischemic Stroke and Transient Ischemic Attack: The Framingham Study

Name: Work Video:
Duration: 3 min 30 s
Natalia S. Rost; Philip A. Wolf; Carlos S. Kase; Margaret Kelly‐Hayes; Halit Silbershatz; Joseph M. Massaro; Ralph B. D’Agostino; Carl Franzblau; Peter W.F. Wilson
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Wolf From the National Heart, Lung, and Blood Institute's Framingham Study (P.A.W., C.S.K., M.K.-H., P.W.F.W.), Framingham, Mass, and the Departments of Neurology (N.S.R., P.A.W., C.S.K., M.K.-H.), Mathematics and Statistics (H.S., R.B.D), Epidemiology and Biostatistics (J.M.M.), Biochemistry (C.F.), and Medicine (P.W.F.W.), Boston University School of Medicine, Boston, Mass."], 'affiliations': [{'raw_affiliation_string': "Philip A. 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Kase From the National Heart, Lung, and Blood Institute's Framingham Study (P.A.W., C.S.K., M.K.-H., P.W.F.W.), Framingham, Mass, and the Departments of Neurology (N.S.R., P.A.W., C.S.K., M.K.-H.), Mathematics and Statistics (H.S., R.B.D), Epidemiology and Biostatistics (J.M.M.), Biochemistry (C.F.), and Medicine (P.W.F.W.), Boston University School of Medicine, Boston, Mass."], 'affiliations': [{'raw_affiliation_string': "Carlos S. 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Massaro From the National Heart, Lung, and Blood Institute's Framingham Study (P.A.W., C.S.K., M.K.-H., P.W.F.W.), Framingham, Mass, and the Departments of Neurology (N.S.R., P.A.W., C.S.K., M.K.-H.), Mathematics and Statistics (H.S., R.B.D), Epidemiology and Biostatistics (J.M.M.), Biochemistry (C.F.), and Medicine (P.W.F.W.), Boston University School of Medicine, Boston, Mass."], 'affiliations': [{'raw_affiliation_string': "Joseph M. 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D'Agostino From the National Heart, Lung, and Blood Institute's Framingham Study (P.A.W., C.S.K., M.K.-H., P.W.F.W.), Framingham, Mass, and the Departments of Neurology (N.S.R., P.A.W., C.S.K., M.K.-H.), Mathematics and Statistics (H.S., R.B.D), Epidemiology and Biostatistics (J.M.M.), Biochemistry (C.F.), and Medicine (P.W.F.W.), Boston University School of Medicine, Boston, Mass."], 'affiliations': [{'raw_affiliation_string': "Ralph B. 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[340], 'Massaro': [342], "D'AgostinoRalph": [392], "D'Agostino": [394], 'FranzblauCarl': [443], 'Franzblau': [444], 'WilsonPeter': [494], 'Wilson': [496], 'Originally': [543], 'published1': [544], 'Nov': [545], '2001https://doi.org/10.1161/hs1101.098151Stroke.': [546], '2001;32:2575–2579AbstractBackground—': [547], 'The': [548, 899, 1267, 1286, 1496, 1793, 1877, 1889, 1929, 1969, 2150, 2669, 3137, 3256, 3280, 3363, 3856], 'role': [549], 'C-reactive': [551, 3677, 3706, 3736, 3789, 3860, 3922, 3948, 3989, 4029, 4062, 4094, 4124], 'protein': [552, 879, 2440, 2444, 2448, 3678, 3707, 3737, 3790, 3861, 3866, 3923, 3949, 3990, 4030, 4063, 4095], '(CRP)': [553], 'as': [554, 924, 1130, 1657, 1731, 1922, 2090, 2104, 2133, 2373, 3003, 3073, 3126, 3350, 3436, 3615], 'a': [555, 580, 892, 925, 1036, 1047, 1141, 1216, 1246, 1441, 1483, 1488, 1506, 1525, 1629, 1904, 1979, 2118, 2462, 2473, 2646, 2674, 2704, 2844, 2854, 2871, 2885, 2921, 2960, 3074, 3098, 3159, 3215, 3236, 3351, 3401, 3450, 3463, 3616, 3746, 4032, 4126], 'novel': [556, 893, 2705], 'plasma': [557, 604, 785, 894, 1201, 1580, 1646, 2076, 2261, 2271, 2456, 2706, 2800, 2810, 2889, 3198, 3274, 3309], 'marker': [558, 895, 2707, 2811, 3075, 4128], 'atherothrombotic': [560, 812, 897, 940, 1454, 2709, 3084], 'disease': [561, 941, 997, 1010, 1033, 1104, 1244, 2643, 2750, 2983, 3104, 3896, 3960, 3995, 4067], 'is': [562, 884, 2628, 2660, 2664, 2696, 2712, 2812, 2904, 3019, 3116, 4031], 'currently': [563], 'under': [564], 'investigation.': [565], 'Previous': [566, 2797], 'studies': [567, 951, 980, 1063, 1078, 1146, 1534, 2745, 2785], 'have': [568, 1045, 1050, 1057, 1105, 1111, 1138, 1269, 1314, 1549, 1565, 2792, 2806, 3176, 3360], 'mostly': [569, 1106], 'related': [570, 603, 1198, 1322, 2460], 'CRP': [571, 598, 605, 648, 667, 701, 766, 786, 905, 923, 944, 990, 1090, 1100, 1155, 1168, 1204, 1323, 1623, 1736, 1766, 1819, 1921, 1932, 1948, 2018, 2077, 2088, 2135, 2262, 2272, 2315, 2355, 2370, 2391, 2457, 2488, 2526, 2587, 2715, 2747, 2761, 2801, 2827, 2841, 2890, 2910, 2980, 3014, 3035, 3150, 3199, 3275, 3310, 3349, 3366, 3395], 'coronary': [573, 1009, 1031, 1124, 3681, 3752, 3794, 4065], 'heart': [574, 1032, 4066], 'disease,': [575], 'were': [576, 625, 650, 663, 672, 679, 1178, 1254, 1261, 1289, 1359, 1382, 1395, 1418, 1437, 1480, 1500, 1522, 1540, 1599, 1614, 1624, 1641, 1685, 1737, 1796, 1825, 1846, 2003, 2079, 2096, 2140, 2322, 2393, 2459, 2941, 3153, 3282], 'often': [577], 'restricted': [578], 'case-control': [581, 1048, 4072], 'design,': [582, 1307], 'failed': [584], 'include': [586, 2683], 'pertinent': [587, 1071], 'risk': [588, 707, 720, 735, 740, 764, 782, 791, 994, 1006, 1015, 1029, 1072, 1158, 1237, 2068, 2127, 2246, 2284, 2296, 2399, 2466, 2492, 2517, 2633, 2755, 2818, 2832, 2848, 2858, 3030, 3082, 3131, 3141, 3315, 3352, 3374, 3412, 3439, 3528, 3553, 3617, 3792, 3822, 3893, 3926, 3992, 4036, 4097], 'factors': [589, 1016, 1073, 1238, 3024, 3550, 3819], 'evaluate': [591], 'joint': [593, 1085], 'net': [595, 1087], 'effect': [596, 1088, 3162], 'on': [599, 657, 665, 1052, 1092, 1108, 1364, 1770, 2799, 3192, 3654, 3779], 'outcome.': [601, 1094], 'We': [602], 'levels': [606, 649, 787, 825, 851, 945, 1091, 1156, 1640, 2273, 2458, 2802, 2842, 2934, 2978, 3015, 3036, 3151, 3272, 3311, 3367], 'incidence': [608, 1339, 2892, 2926], 'first': [610, 1207, 2129, 2165, 2248, 2286, 2367, 2401, 2468, 2494, 2519, 2894], 'ischemic': [611, 615, 689, 709, 794, 877, 1184, 1208, 1335, 1451, 2130, 2249, 2287, 2402, 2469, 2495, 2520, 2639, 2804, 2834, 2895, 2928, 3033, 3317, 3355, 3387, 3530], 'stroke': [612, 795, 1129, 1161, 1181, 1209, 1336, 1362, 1398, 1464, 1467, 1499, 2169, 2250, 2496, 2787, 2805, 2881, 2896, 2929, 3318, 3356, 3388, 3430, 4040], 'or': [613, 958, 969, 1110, 1121, 1182, 1210, 1337, 1399, 1459, 1465, 1511, 1555, 1662, 1666, 2170, 2251, 2346, 2415, 2497, 2574, 2866, 2897, 3319, 3357, 3389, 3557, 3826], 'transient': [614, 1183], 'attack': [616, 1185], '(TIA)': [617, 1186], 'in': [618, 698, 726, 734, 763, 798, 849, 865, 869, 949, 981, 998, 1035, 1074, 1169, 1212, 1233, 1245, 1471, 1476, 1695, 1897, 1926, 1933, 1962, 2176, 2182, 2264, 2274, 2299, 2310, 2332, 2379, 2404, 2465, 2471, 2485, 2525, 2537, 2542, 2570, 2581, 2589, 2620, 2720, 2763, 2770, 2847, 2857, 2899, 2913, 2924, 2947, 2951, 2990, 3042, 3086, 3128, 3135, 3145, 3169, 3181, 3231, 3276, 3284, 3321, 3335, 3368, 3399, 3417, 3432, 3447, 3560, 3588, 3638, 3679, 3709, 3741, 3796, 3829, 3867, 3897, 3955, 3961, 3996, 4041, 4068], 'original': [622, 1175, 1392], 'cohort.Methods—': [623], 'There': [624], '591': [626, 1385], 'men': [627, 697, 743, 773, 1386, 2007, 2325, 2405, 2538, 2571, 2876, 2915, 3289, 3303, 3323, 3343, 3406], '871': [629, 1388], 'women': [630, 714, 747, 776, 1389, 2009, 2309, 2329, 2484, 2543, 2575, 2837, 2878, 3408], 'free': [631, 1179, 1363, 1396, 2879], 'stroke/TIA': [633, 710, 2131, 2288, 2403, 2470, 2521], 'during': [634, 1215, 1340, 1681], 'their': [635, 642, 1191, 3017], '1980': [636, 1192, 1376], '1982': [638, 1194], 'clinic': [639, 1195, 1373, 1413], 'examinations,': [640], 'when': [641, 2938], 'mean': [643], 'age': [644, 2378, 2555], 'was': [645, 1231, 1655, 1691, 1729, 1768, 1787, 1856, 1880, 1895, 1912, 1937, 1959, 1976, 2000, 2121, 2153, 2205, 2306, 2371, 2426, 2476, 2535, 2550, 2599, 2774, 3445], '69.7': [646], 'years.': [647, 1266, 2159], 'measured': [651, 1164, 1625, 1738], 'by': [652, 822, 834, 912, 1291, 1482, 1502, 1524, 1626, 1648, 1744, 1752, 1858, 1869, 1882, 1914, 2010, 2081, 2086, 2098, 2213, 2553, 3449, 3462], 'using': [653, 1745, 1915, 2011, 2087, 2099], 'an': [654, 881, 885, 1740, 1898, 1923, 2281, 2397, 2523, 2697, 2813, 3028, 3080, 3110, 3285, 3749], 'enzyme': [655, 1742, 1899], 'immunoassay': [656, 1743, 1900], 'previously': [658], 'frozen': [659, 1416], 'serum': [660, 824, 1612, 1785, 1920, 2977, 3705, 3863], 'samples.': [661], 'Analyses': [662], 'based': [664, 3191], 'sex-specific': [666, 2012, 2335], 'quartiles.': [668], 'ratios': [670], '(RRs)': [671], 'derived,': [673], 'series': [675, 2510, 2675], 'trend': [677, 733, 2119, 2512, 2549, 2948], 'analyses': [678, 3337], 'performed.Results—': [680], 'During': [681, 2160], '12': [682, 1341], '14': [684, 1343, 2158], 'years': [685, 1344], 'follow-up,': [687], '196': [688, 2163], 'strokes': [690, 2618], 'TIAs': [692], 'occurred.': [693], 'Independent': [694, 778], 'age,': [696, 1582, 2057, 2429, 2602], 'highest': [700, 2334, 2487, 2825, 2840, 3370], 'quartile': [702, 2102, 2136, 2258, 2277, 2313, 2368, 2529, 2534, 2911, 3371], 'had': [703, 715, 1468, 1550, 2280, 2829, 2843], '2': [704, 1528, 1710, 2290, 2390], 'times': [705, 718, 1808, 1849, 2291], '(RR=2.0,': [711, 2326], 'P=0.027),': [712], 'almost': [716, 1421, 2289], '3': [717, 2381], '(RR=2.7,': [721], 'P=0.0003)': [722], 'compared': [723, 2767], 'with': [724, 808, 907, 954, 975, 1013, 1061, 1273, 1463, 1693, 1739, 1754, 1809, 1850, 1978, 1987, 2255, 2270, 2396, 2760, 2768, 2823, 2838, 2908, 2932, 3013, 3054, 3062, 3118, 3147, 3155, 3453, 3562, 3640, 3745, 3831], 'those': [725, 973, 2298, 2769, 3433], 'lowest': [728, 2101], 'quartile.': [729], 'Assessment': [730], 'across': [736, 765], 'quartiles': [737, 767, 2013, 2078, 2089, 2336, 2392], 'showed': [738, 2751], 'unadjusted': [739, 2282, 2515], 'increase': [741, 762, 2464, 2524, 2846, 2856, 2923, 3382], 'for': [742, 752, 771, 860, 896, 1017, 1239, 1420, 1446, 1498, 1516, 1575, 1798, 1832, 1871, 2006, 2051, 2056, 2075, 2155, 2297, 2308, 2324, 2377, 2428, 2483, 2522, 2601, 2638, 2645, 2756, 2959, 3227, 3354, 3413, 3428, 3440, 3619, 3774, 4129], '(RR=1.347,': [744], 'P=0.0025)': [745], '(RR=1.441,': [748], 'P=0.0001).': [749], 'After': [750], 'adjustment': [751, 2425, 2504, 2556, 2564, 2598], 'smoking,': [753, 1588, 2058, 2430, 2603, 2966], 'total/HDL': [754], 'cholesterol,': [755, 2062, 2218, 2222, 2434, 2607, 2973], 'systolic': [756, 1584, 1714, 2063, 2435, 2608, 2967], 'blood': [757, 1281, 1380, 1585, 1597, 1669, 1689, 1715, 1723, 2064, 2226, 2436, 2609, 2968], 'pressure,': [758, 1586, 2065, 2227, 2437, 2610, 2969], 'diabetes,': [760], 'remained': [768, 2499], 'statistically': [769, 2479], 'significant': [770, 2480], 'both': [772, 2265, 2900, 2914], '(P=0.0365)': [774], '(P=0.0084).Conclusions—': [777], 'other': [780, 1070, 3336, 3951], 'cardiovascular': [781, 929, 996, 1103, 1113, 1243, 2749, 3133, 3507, 3895, 3929, 3959, 3994], 'factors,': [783], 'elevated': [784, 850, 1713, 3308], 'significantly': [788, 2254, 2500, 3312, 3381], 'predict': [789, 3313], 'future': [793, 2820, 3928], 'TIA': [797, 1211, 1338, 2252, 2347, 2416, 2498, 2883, 2898, 2931, 3320, 3358], 'elderly.An': [800], 'increasing': [801, 2257], 'body': [802], 'evidence': [804], 'has': [805, 918, 946, 1079, 2716], 'linked': [806], 'inflammation': [807, 816, 890, 2791, 3092, 3954], 'pathogenesis': [810], 'stroke.': [813, 3624], 'Infections': [814], 'may': [817, 856, 871, 3108, 3157, 3202, 3294, 3380, 3397, 3419], 'promote': [818], 'atherosclerosis': [819, 2663, 2672], 'thrombosis': [821], 'elevating': [823], 'fibrinogen,1': [827], 'leukocytes,2': [828], 'clotting': [829], 'factors,3': [830], 'cytokines4': [832], 'altering': [835], 'metabolism': [837], 'functions': [839], 'endothelial': [841], 'cells': [842], 'monocyte': [844], 'macrophages.5': [845], 'Low-grade': [846], 'infections,': [847], 'reflected': [848], 'various': [853], 'acute-phase': [854, 882, 2694], 'proteins,6': [855], 'be': [857, 3040, 3097, 3109], 'partly': [858], 'responsible': [859], 'inflammatory': [862, 2688, 2722], 'processes': [863], 'observed': [864, 2323, 3230], 'atherosclerotic': [866, 1102, 3103], 'lesions,': [867], 'which': [868, 3201], 'turn': [870], 'relate': [872], 'occurrence': [875], 'symptoms.C-reactive': [878], '(CRP),': [880], 'reactant,': [883], 'indicator': [886, 2698], 'underlying': [888, 2667, 2700, 3102], 'systemic': [889, 2701], 'disease.': [898, 3683, 4102], 'recent': [900, 2740], 'use': [901, 1627, 1658, 3393], 'highly': [903, 1755, 3011], 'sensitive': [904, 2987, 4127], 'assays,': [906], 'international': [908], 'reference': [909], 'standards': [910], 'set': [911], 'World': [914, 3664], 'Health': [915, 3665, 4003, 4008], 'Organization': [916], '(WHO),7': [917], 'enhanced': [919], 'usefulness': [921], 'reliable': [926], 'predictor': [927, 2815], 'events.': [930, 3034, 3415], 'A': [931, 1909, 2303, 2739, 3865], 'strong': [932, 2886, 4033], 'consistent': [934, 2907, 3117], 'association': [935, 2305], 'between': [936, 2888], 'clinical': [937], 'manifestations': [938], 'baseline': [943, 1154, 1200, 2260, 2826, 3149], 'been': [947, 1139, 1270, 1315, 1469, 2793], 'described': [948], 'epidemiological': [950, 1145, 2784], 'patients': [953, 1694, 3561, 3639, 3744, 3830], 'acute': [955, 3032, 3268, 3593, 3641], 'myocardial': [956, 959, 967, 1119, 2864, 3143, 3555, 3594, 3621, 3642, 3710, 3742, 3824], 'ischemia8': [957], 'infarction,9,10': [960], 'stable': [961, 3797], 'unstable': [963, 3589, 3799, 3869], 'angina': [964, 976, 3563, 3590, 3832], 'pectoris,11': [965], 'infarction': [968, 1120, 2865, 3144, 3556, 3825], 'recurrent': [970], 'ischemia': [971, 3269, 3711], 'among': [972, 1011, 2758, 3931], 'hospitalized': [974, 1470], 'pectoris.12,13': [977], 'Large': [978], 'prospective': [979, 1144, 2744, 2783, 2868, 3258], 'apparently': [982, 3898, 3932], 'healthy': [983, 1041, 3088, 3899, 3933], 'subjects': [984, 1214, 1268, 1302, 1358, 1409, 1462, 1603, 2204, 3146], 'confirmed': [985, 3334], 'prognostic': [987, 3857], 'relevance': [988], '(1)': [992], 'men,14': [999], 'women,15,16': [1000], 'elderly17,18;': [1003], '(2)': [1004], 'fatal': [1008, 1116, 4039], 'smokers': [1012], 'multiple': [1014, 3023], 'atherosclerosis19;': [1018], '(3)': [1019], 'development': [1021, 1448, 3423], 'peripheral': [1023, 4100], 'vascular': [1024, 2851, 4101], 'disease20;': [1025], '(4)': [1027], '(CHD)': [1034], 'large': [1037, 2872, 3339, 3403], 'cohort': [1038, 1176, 1393, 2151, 2874, 3259, 3287], 'initially': [1040], 'middle-aged': [1042], 'men.21Most': [1043], 'researchers': [1044], 'used': [1046, 1112, 2372], 'design,8–13': [1049], 'focused': [1051, 1107], 'selected': [1053], 'subject': [1054], 'populations,14–21': [1055], 'largely': [1058], 'investigated': [1059], 'men,8–14,20,21': [1060], 'few': [1062, 1142, 1489, 2782], 'women.15–17': [1065], 'Furthermore,': [1066, 2946], 'limited': [1067], 'availability': [1068], 'some': [1075], 'these': [1077, 1213, 1424, 3066], 'not': [1080, 2383, 2551, 2566, 2982, 3093, 3175, 3203, 3225], 'permitted': [1081], 'determination': [1082, 1982], 'Last,': [1095], 'research': [1097], 'findings': [1098, 3189, 3247], 'linking': [1099], 'CHD8–11,13–17,19,21': [1109], '"events"': [1114], '(encompassing': [1115], 'CHD,': [1117], 'nonfatal': [1118], 'stroke,': [1122, 1452], 'revascularization': [1125], 'procedures)': [1126], 'instead': [1127], 'specific': [1132, 2677, 2984], 'outcome': [1133, 2862], 'interest,15,16': [1135], 'there': [1137, 1253], 'only': [1140, 1473, 3020, 3094], 'large-scale': [1143], 'stroke.14': [1148], 'To': [1149, 1943], 'address': [1150, 3186], 'issue': [1152], 'subsequent': [1160], 'events,': [1162], 'we': [1163, 1321, 3173], 'concentration': [1166, 1930, 3708, 4092], 'members': [1170], 'who': [1177, 1260, 1394, 1410, 3152, 3409], 'at': [1187, 1325, 1347, 1551, 1604, 1616, 1700, 1801, 1835, 1874, 1903, 2142, 2186, 3411, 3438], 'time': [1189, 1370], 'examination': [1196, 1287, 1348], 'concentrations': [1202, 1621, 1734, 1917, 2263], 'incident': [1206, 1450, 3386], '12-': [1217, 1442], '14-year': [1219, 1444], 'follow-up': [1220, 1313, 1346, 3217], 'period.Subjects': [1221], 'MethodsSubjects': [1223], 'Definition': [1225], 'Clinical': [1227], 'OutcomeThe': [1228], 'begun': [1232], '1948': [1234], 'explore': [1236], 'consequences': [1241], 'longitudinal': [1247], 'community-based': [1248, 2873], 'population': [1249, 1403], 'sample.': [1250], 'At': [1251, 1368, 1838], 'entry,': [1252], '5209': [1255], 'male': [1256], 'female': [1258], 'participants': [1259, 1425, 3213], 'aged': [1262], '28': [1263], '62': [1265], 'examined': [1271], 'biennially': [1272], 'routine': [1274], 'assessment': [1275], 'medical': [1277], 'history,': [1278], 'physical': [1279], 'examination,': [1280, 1414], 'tests,': [1282], '12-lead': [1284], 'ECGs.': [1285], 'procedures': [1288], 'approved': [1290], 'Institutional': [1293], 'Review': [1294], 'Board': [1295], 'Medical': [1298], 'Center,': [1299], 'all': [1301, 1422, 1602, 2650], 'gave': [1303], 'informed': [1304], 'consent.': [1305], 'response': [1308, 1970, 2569, 2991, 3099], 'rates,': [1309], 'completeness': [1311], 'reported': [1316], 'elsewhere.22For': [1317], 'present': [1319, 1577, 3183, 3233, 3331], 'study,': [1320, 3234], 'level': [1324, 1671], 'biennial': [1326, 1605, 2143], 'examinations': [1327, 1374, 1606, 2144], '16': [1328, 1607, 2145, 2188], '17': [1330, 2147], '(1980': [1331], '1982)': [1333], '23': [1349], '(1994).': [1350], 'Of': [1351], 'initial': [1353], 'cohort,': [1356], '2999': [1357], 'alive': [1360], 'January': [1365], '1,': [1366], '1982.': [1367], 'from': [1375, 1384, 1601, 1643, 1939, 1951, 2527, 2870, 3465, 4000], '1982,': [1378, 1547], 'nonfasting': [1379, 1645], 'specimens': [1381, 1417, 1598], 'obtained': [1383, 1600, 3283], 'TIA.': [1400, 1460, 3390], 'This': [1401, 2902, 3115], 'study': [1402, 3184, 3212, 3246, 3278, 3332, 3444, 3920], 'represented': [1404], 'approximately': [1405], '60%': [1406], 'living': [1408, 1434], 'attended': [1411], 'available': [1419, 1541], '(an': [1426], 'overall': [1427], 'inclusion': [1428, 3347], 'rate': [1429], '50%': [1431], 'subjects).': [1435], 'Subjects': [1436], 'followed': [1438, 1868, 2154], 'up': [1439, 2156], 'over': [1440, 3214], 'period': [1445], 'including': [1453, 2724, 2965], 'brain': [1455, 1537, 1560, 2658], 'infarction,': [1456, 3622], 'cerebral': [1457], 'embolism,': [1458], 'Most': [1461], 'suspected': [1466], 'general': [1474], 'hospital': [1475], 'where': [1478, 2375], 'they': [1479], 'evaluated': [1481], 'neurologist': [1486], 'within': [1487, 1492, 2942], 'days': [1490], '(often': [1491], 'hours)': [1493], 'after': [1494, 1699, 2502, 2957, 3754], 'onset.': [1495], 'criteria': [1497], 'met': [1501], 'presence': [1504], 'neurological': [1507], 'deficit': [1508], 'sudden': [1510, 3558, 3827], 'rapid': [1512], 'onset': [1513], 'that': [1514, 2475, 2682, 2714, 2752, 2808, 3025, 3071, 3166, 3267, 3307], 'persisted': [1515, 2956], '≥24': [1517], 'hours,': [1518], 'events': [1521, 2167, 3085, 3134, 3795, 3930], 'adjudicated': [1523], 'panel': [1526], 'neurologists.': [1529], 'CT': [1530, 1554], 'scans': [1531], 'MRI': [1533, 1556], 'arteries': [1539], 'confirm': [1543], 'diagnosis;': [1545], 'since': [1546], '91.5%': [1548], 'least': [1552, 1701], '1': [1553, 3500], 'scan': [1557], 'arteries,': [1562], 'many': [1564, 2717], 'undergone': [1566], '>1': [1567], 'study.23Assessment': [1568], 'FactorsBaseline': [1572], 'covariables': [1573], 'assessed': [1574, 1642], 'analysis': [1578, 2120], 'included': [1579], 'CRP,': [1581, 2690, 2936, 3072], 'sex,': [1583], 'cigarette': [1587, 1679], 'total': [1589, 2059, 2431, 2604, 2970], 'HDL': [1591, 1638, 2061, 2433, 2606, 2972], 'cholesterol': [1592, 1639, 2208], 'levels,': [1593, 3200], 'diabetes.': [1595, 2975], 'Nonfasting': [1596], '17,': [1609], 'aliquots': [1613], 'stored': [1615], '−20°C': [1617], 'until': [1618], 'mid-1997.': [1619], 'Plasma': [1620, 2350, 2419, 4091], 'standardized': [1630], 'commercial': [1631], 'biochemical': [1632], 'assay': [1633], '(Hemagen': [1634], 'Diagnostics).': [1635], 'Total': [1636, 2201], 'fresh': [1644], 'samples': [1647, 1936], 'standard': [1649, 1910, 1941, 1953, 1957, 1989], 'Lipid': [1650], 'Research': [1651], 'Clinics': [1652], 'techniques.24': [1653], 'Diabetes': [1654], 'defined': [1656, 1730], 'insulin': [1660], 'preparations': [1661], 'oral': [1663], 'hypoglycemic': [1664], 'agents': [1665], 'any': [1667, 2850], 'recorded': [1668, 1692, 2141], 'glucose': [1670], '≥11.1': [1673], 'mmol/L': [1674], '(≥200': [1675], 'mg/dL).': [1676], 'Persons': [1677], 'reporting': [1678], 'smoking': [1680], 'past': [1683], 'year': [1684], 'considered': [1686], 'smokers.': [1687], 'Systolic': [1688], 'pressure': [1690, 1716, 1724], 'sitting': [1697], 'position': [1698], '5': [1702], 'minutes': [1703, 1800, 1834, 1873], 'rest.': [1705], 'On': [1706, 1994], 'basis': [1708], 'consecutive': [1711], 'measurements,': [1712], '≥140': [1718], 'mm': [1719, 1727, 2228], 'Hg': [1720, 1728], 'and/or': [1721], 'diastolic': [1722], '≥90': [1726], 'hypertension.Laboratory': [1732], 'ProceduresSerum': [1733], 'ultrasensitive': [1741], 'monospecific': [1746], 'polyclonal': [1747, 1763], 'monoclonal': [1749], 'antibodies': [1750], 'produced': [1751, 2989], 'immunization': [1753], 'purified': [1756], 'CRP.': [1757, 2338], 'Briefly,': [1758], 'IgG': [1760], 'fraction': [1761], 'goat': [1764], 'anti-human': [1765, 1818], 'antiserum': [1767], 'immobilized': [1769], 'inner': [1772], 'surface': [1773], 'microwell': [1775], 'plates.': [1776], 'One': [1777], 'hundred': [1778], 'microliters': [1779], '(at': [1780], '1:100': [1781], 'dilution)': [1782], 'each': [1784, 1828, 1927, 2108, 2256, 2624], 'sample': [1786], 'introduced': [1788], 'into': [1789], 'test': [1791, 1935], 'wells.': [1792], 'titer': [1794], 'plates': [1795, 1845], 'incubated': [1797, 1831], '30': [1799, 1833, 1872], 'room': [1802, 1836, 1875], 'temperature': [1803], 'then': [1805], 'washed': [1806], '4': [1807, 1848], 'rinsing': [1810, 1851], 'solution.': [1811, 1852], 'Aliquots': [1812], '(100': [1813], 'μL)': [1814], 'secondary': [1816], 'rabbit': [1817], 'antibody': [1820], 'conjugated': [1821], 'horseradish': [1823], 'peroxidase': [1824, 1854], 'added': [1826], 'well': [1829], 'temperature.': [1837, 1876], 'end': [1840], 'incubation,': [1843], 'rinsed': [1847], 'Horseradish': [1853], 'activity': [1855, 3057], 'determined': [1857, 1938], 'addition': [1860, 3364], '100': [1862], 'μL': [1863, 1885], 'substrate': [1866], '3,3′,5,5′-tetramethylbenzidine,': [1867], 'incubation': [1870], 'enzymatic': [1878], 'reaction': [1879], 'stopped': [1881], 'transferring': [1883], '50': [1884], '1N': [1887], 'H2SO4.': [1888], 'optical': [1890], 'density': [1891], 'product': [1894], 'quantified': [1896], 'plate': [1901], 'reader': [1902], 'wavelength': [1905], '450': [1907], 'nm.': [1908], 'curve': [1911, 1990], 'generated': [1913, 2080], 'known': [1916, 3038], 'human': [1919], 'internal': [1924], 'control': [1925], 'experiment.': [1928], 'curve.': [1942], 'verify': [1944], 'accuracy': [1946], 'results': [1949, 3251, 3300, 3328, 3999], 'interpolated': [1950], 'curve,': [1954], 'WHO': [1956, 3651, 3657], 'preparation7,25': [1958], 'serially': [1960], 'diluted': [1961], 'working': [1964], 'range': [1965], 'kit.': [1968], 'Hemagen': [1973], 'CRP150': [1974], 'Kit': [1975], 'linear': [1977, 2905], 'coefficient': [1980, 1999], '(r2)': [1983], '>0.99': [1984], 'colinear': [1986], 'assay.': [1993], 'split': [1995], 'specimens,': [1996], 'correlation': [1998], '0.86.Statistical': [2001], 'AnalysesAnalyses': [2002], 'performed': [2004, 2122, 2794], 'separately': [2005], '(Q1': [2014], 'Q4)': [2016], '(men:': [2019, 2557], 'Q1=0': [2020, 2035], '1.08,': [2022], 'Q2=1.10': [2023], '3.0,': [2025], 'Q3=3.03': [2026], '6.80,': [2028], 'Q4=6.90': [2030], '48.30': [2032], 'μg/mL;': [2033], 'women:': [2034, 2560], '1.00,': [2037], 'Q2=1.02': [2038], '3.19,': [2040], 'Q3=3.20': [2041], '7.31,': [2043], 'Q4=7.33': [2045], '50.20': [2047], 'μg/mL).Unadjusted,': [2048], 'bivariate': [2049], '(adjusted': [2050, 2055], 'age),': [2052], 'multivariate': [2054, 2114, 2452, 2503], 'diabetes)': [2067], 'ratio': [2069], '(RR)': [2070], 'estimates': [2071], '(with': [2072], '95%': [2073], 'CIs)': [2074], 'Cox': [2082, 2115], 'proportional': [2083], 'hazards': [2084], 'modeling': [2085], 'independent': [2092, 2814], 'variable.': [2093], 'These': [2094, 2918], 'RRs': [2095], 'derived': [2097], '(Q1)': [2103], 'referent': [2106], 'group.For': [2107], 'unadjusted,': [2111], 'bivariate,': [2112], 'regression': [2116], 'analyses,': [2117, 2513, 2949], 'determine': [2124], 'whether': [2125], 'increased': [2132, 2253, 2398, 2501, 2933, 3029, 3081], 'increased.ResultsStudy': [2137], 'participant': [2138], 'characteristics': [2139], '(Table': [2148, 2267, 2578], '1).': [2149], '(n=1462)': [2152], 'this': [2161, 2548, 2809, 2954, 3187, 3220, 3293], 'time,': [2162], '(13.4%)': [2164], 'cerebrovascular': [2166, 2640, 2642, 3414, 3442], '(ischemic': [2168], 'TIA)': [2171], 'occurred;': [2172], '82': [2173], '(13.9%)': [2174], 'occurred': [2175, 2181], 'men,': [2177, 2472], '114': [2179], '(13.1%)': [2180], 'women.': [2183, 2407, 2917, 3325, 3934, 3962], 'Subject': [2184], 'Characteristics': [2185], 'Exams': [2187], '17Men': [2190], '(N=591': [2191], '[40.4%])Women': [2192], '(N=871': [2193], '[59.6%])Data': [2194], 'are': [2195, 2981, 2986, 3010, 3037, 3190, 3333, 3410], 'mean±SD': [2196], '(range),': [2197], 'unless': [2198], 'otherwise': [2199, 3087], 'specified.': [2200], 'number': [2202, 2961, 3404], '1462.*To': [2206], 'convert': [2207], 'values': [2209, 2762, 2828, 2940, 3396], 'mmol/L,': [2211], 'multiply': [2212], '0.02586.Age,': [2214], 'y69.1±6.7': [2215], '(60–90)70.2±7.1': [2216], '(59–91)Total': [2217], 'mg/dL*215.2±37': [2219], '(105–379)239.1±40.4': [2220], '(123–395)HDL': [2221], 'mg/dL*43.7±13.4': [2223], '(20–134)53.5±14.7': [2224], '(20–112)Systolic': [2225], 'Hg140.5±19.7': [2229], '(90–220)141.6±21.8': [2230], '(86–225)Smoking,': [2231], 'n': [2232, 2237], '(%': [2233, 2238], 'total)125': [2234], '(21.15)207': [2235], '(23.80)Diabetes,': [2236], 'total)71': [2239], '(12.01)68': [2240], '(7.8)CRP,': [2241], 'μg/mL5.4±7.3': [2242], '(0–48.3)6.2±8.4': [2243], '(0–50.2)Unadjusted': [2244], 'relative': [2245, 2283, 2295, 2320, 2491, 2516, 2754], 'sexes': [2266], '2).': [2268], 'Men': [2269, 2822], 'third': [2276, 2312, 2766, 2773], '(≥3.03': [2278], 'μg/mL)': [2279], 'greater': [2292, 2319, 3041, 3314], 'than': [2293, 2615], 'Q1': [2300], '(RR=1.9,': [2301], 'P=0.037).': [2302], 'similar': [2304], 'found': [2307], '(RR=1.8,': [2316], 'P=0.033).': [2317], 'Even': [2318], 'risks': [2321], 'P=0.028)': [2327], '(RR=2.9,': [2330], 'P=0.0001)': [2331], 'Unadjusted': [2339], 'Relative': [2340, 2409], 'Incident': [2343], 'According': [2348, 2417], 'CRPQuartiles': [2353], 'Concentration*Men': [2356], '(n=82/591)Women': [2357], '(n=114/871)Range,': [2358], 'μg/mLRR95%': [2359, 2361], 'CIPRange,': [2360], 'CIP*In': [2362], 'calculations': [2363], 'RRs,': [2365], 'referent,': [2374], 'RR=1.Q10–1.08Referent……0–1.00Referent……Q21.10–3.00.90.48–1.920.9061.02–3.191.20.66–2.280.507Q33.03–6.801.91.07–3.690.0373.20–7.311.81.02–3.230.033Q46.90–48.302.01.09–3.780.0287.33–50.202.91.69–5.070.0001Adjustment': [2376], 'Table': [2380, 2507, 2952], 'did': [2382, 2565], 'attenuate': [2384, 2567], 'response,': [2386], 'top': [2389, 2765], 'consistently': [2394], 'associated': [2395], 'Adjusted': [2408], 'First': [2412], 'CRPAdjustment*MenWomenRR95%': [2422], 'CIPRR95%': [2423, 2595, 2596], 'CIP*Multivariate': [2424, 2597], 'made': [2427, 2600], 'diabetes.C-reactive': [2439], 'Q2': [2441], 'Age0.90.48–1.910.9041.20.66–2.290.468': [2442], 'Multivariate0.90.46–1.860.8391.20.63–2.270.508C-reactive': [2443], 'Q3': [2445], 'Age1.91.04–3.610.041.81.03–3.260.03': [2446], 'Multivariate1.50.80–2.870.2591.60.89–2.930.087C-reactive': [2447], 'Q4': [2449, 2455], 'Age2.01.10–3.790.0272.71.59–4.790.0003': [2450], 'Multivariate1.60.87–3.130.1232.11.19–3.830.008After': [2451], 'adjustment,': [2453], '1.6-fold': [2463], 'result': [2474], 'no': [2477], 'longer': [2478], '(P=0.123).': [2481], 'However,': [2482, 2781, 3219], 'quartile,': [2489], '(RR=2.1,': [2505], 'P=0.008;': [2506], '3).In': [2508], 'one': [2528, 2691, 3021], 'next': [2532], 'higher': [2533], '1.347': [2536], '(P=0.0025)': [2539], '1.441': [2541], '(P=0.0001).': [2544], 'Statistical': [2545], 'significance': [2546], 'altered': [2552], 'RR=1.346,': [2558], 'P=0.0027;': [2559], 'RR=1.411,': [2561], 'P=0.0002).': [2562], 'Multivariate': [2563], '(RR=1.248,': [2572], 'P=0.0365)': [2573], '(RR=1.288,': [2576], 'P=0.0084)': [2577], '4).': [2579], 'Trend': [2580], 'Stroke/TIA': [2585], 'Across': [2586], 'Quartiles': [2588], '1462': [2590], 'ParticipantsData': [2593], 'CategoryUnadjustedAge-AdjustedMultivariate-Adjusted*RR95%': [2594], 'diabetes.Men': [2612], '(n=591)1.3471.105–1.6420.00251.3461.104–1.6420.00271.2481.012–1.5390.0365Women': [2613], '(n=871)1.4411.210–1.7130.00011.4111.188–1.6770.00021.2881.073–1.5460.0084DiscussionMore': [2614], '700': [2616], '000': [2617], 'occur': [2619], 'United': [2622], 'States': [2623], 'year,26': [2625], 'it': [2627], 'paramount': [2629], 'identify': [2631], 'new': [2632, 3425], 'markers': [2634, 2789, 2988, 3952], 'preventive': [2636], 'strategies': [2637, 3427], 'disease.Ischemic': [2641], 'accounts': [2644], 'substantial': [2647, 3138], 'proportion': [2648], 'strokes.27': [2651], 'Although': [2652], 'proximate': [2654], 'cause': [2655], 'most': [2657], 'infarcts': [2659], 'thrombus': [2661], 'formation,': [2662], 'chief': [2666], 'cause.28,29': [2668], 'lesions': [2670], 'represent': [2673], 'cellular': [2678], 'molecular': [2680], 'responses': [2681], 'lipoprotein,': [2684], 'hematologic,': [2685], 'mechanical,': [2686], 'components.29': [2689], 'reactants,': [2695], 'inflammation30': [2702], 'disease.31–33': [2710], 'It': [2711], 'likely': [2713], 'pathophysiological': [2718], 'roles': [2719], 'process,': [2723], 'binding': [2725], 'phosphocholine': [2727], 'recognition': [2729], 'foreign': [2731], 'pathogens': [2732], 'phospholipid': [2734], 'constituents': [2735], 'damaged': [2737], 'cells.30': [2738], 'meta-analysis': [2741], 'several': [2743], 'CHD': [2757], 'individuals': [2759, 3045, 3053, 3061, 3434], 'bottom': [2772], '1.7': [2775], '(95%': [2776], 'CI': [2777], '1.4': [2778], '2.1).31': [2780], 'date.': [2796], 'data': [2798, 2869, 2919, 3067, 3180, 3281], 'suggested': [2807], 'stroke.14,15': [2821], 'twice': [2830], 'stroke,14': [2835], '5-fold': [2845], 'event': [2852], '7-fold': [2855], 'combined': [2861], 'stroke.15Our': [2867], 'demonstrate': [2884, 2920], 'relationship': [2887, 2903, 2955, 3229], 'sexes.': [2901], 'gradation': [2912], 'graded': [2922], 'even': [2937], 'normal': [2944], 'range.': [2945], 'shown': [2950], '4,': [2953], 'adjusting': [2958], 'potential': [2963], 'confounders,': [2964], 'Elevated': [2976], 'but': [2985, 3106, 4034], 'tissue': [2993], 'injury,': [2994], 'infectious': [2995], 'agents,': [2996, 3124], 'immunologic': [2997], 'stimuli,': [2998], 'inflammation.': [3000], 'Cytokines': [3001], 'such': [3002, 3125, 3240], 'interleukin-6,': [3004], 'interleukin-1,': [3005], 'tumor': [3007], 'necrosis': [3008], 'factor-α': [3009], 'correlated': [3012], 'function.34Inflammation': [3018], 'can': [3026], 'foster': [3027], 'smokers,35,36': [3043], 'obese': [3044], '(body': [3046], 'mass': [3047], 'index': [3048], '>130%': [3049], 'ideal),': [3052], 'abnormal': [3055], 'fibrinolytic': [3056], '(plasmin-antiplasmin': [3058], 'complex),': [3059], 'subclinical': [3063], 'atherosclerosis.37,38': [3064], 'Overall,': [3065], 'support': [3068], 'view': [3070], 'low-level': [3077], 'inflammation,': [3078], 'predicts': [3079], 'individuals.': [3089], 'In': [3090], 'addition,': [3091], 'appears': [3095], 'process': [3105], 'also': [3107], 'integral': [3111], 'part': [3112, 3448], 'it.36': [3114], 'beneficial': [3120, 3160], 'effects': [3121], 'anti-inflammatory': [3123, 3161], 'aspirin,': [3127, 3890], 'reducing': [3129], 'men.14': [3136], 'reduction': [3139], 'high': [3148], 'treated': [3154], 'aspirin14': [3156], 'suggest': [3158], 'drug': [3165], 'becomes': [3167], 'detectable': [3168], 'low-risk': [3170], 'patients.': [3171], 'Unfortunately,': [3172], 'do': [3174], 'adequate': [3177], 'aspirin': [3178], 'intake': [3179], 'issue.Our': [3188], '1-time': [3194], 'measurement': [3195], 'completely': [3204], 'accurately': [3206], 'reflect': [3207], 'status': [3209], 'prolonged': [3216], 'period.': [3218], 'source': [3221], 'variability': [3223], 'could': [3224], 'account': [3226], 'because': [3235], 'random': [3237], 'misclassification': [3238], 'nature': [3241], 'would': [3242, 3359], 'tend': [3243], 'underestimate': [3245], 'bias': [3249], 'toward': [3252], 'null': [3254], 'hypothesis.': [3255], 'nested': [3257, 4071], 'design': [3260], 'allows': [3261], 'us': [3262], 'exclude': [3264], 'possibility': [3266], 'affected': [3270], 'participants.': [3279], 'elderly': [3286, 3322, 3379, 4042], 'women,': [3291, 3345], 'limit': [3295], 'applicability': [3297], 'younger': [3302], 'women.We': [3305], 'conclude': [3306], 'If': [3326], 'population-based': [3340], 'cohorts': [3341], 'factor': [3353, 3375, 3618, 4037], 'important': [3361], 'implications.': [3362], 'profile': [3376], 'predictability': [3384], 'Thus,': [3391], 'aid': [3398], 'identifying': [3400], 'potentially': [3402], 'This,': [3416], 'turn,': [3418], 'lead': [3420], 'treatment': [3426], 'primary': [3429], 'prevention': [3431], 'identified': [3435], 'being': [3437], 'developing': [3441, 4099], 'disease.This': [3443], 'supported': [3446], 'contract': [3451], '(NO1-HC-38038)': [3452], 'Institute': [3460, 3468], 'grant': [3464], 'Neurological': [3470, 3480], 'Disorders': [3471], '(5-RO1-NS-17950-19).FootnotesCorrespondence': [3474], 'Genetics,': [3483], '715': [3489], 'Albany': [3490], 'St,': [3491], 'B-608,': [3492], 'MA': [3494], '02118-2526.': [3495], 'E-mail': [3496], '[email': [3497], 'protected]': [3498], 'References': [3499], 'Ernst': [3501, 3515], 'E,': [3502, 3516], 'Koenig': [3503, 4108], 'W.': [3504], 'Fibrinogen': [3505], 'risk.': [3508], 'Vasc': [3509, 4013, 4046], 'Med.': [3510, 3646, 3837, 3874, 3904, 3966], '1997;': [3511, 3802, 3905, 4015], '2:': [3512], '115–125.CrossrefMedlineGoogle': [3513], 'Scholar2': [3514], 'Hammerschmidt': [3517], 'DE,': [3518], 'Bagge': [3519], 'U,': [3520], 'Matrai': [3521], 'A,': [3522, 3700, 3724, 4119], 'Dormandy': [3523], 'JA.': [3524], 'Leukocytes': [3525], 'diseases.': [3531], 'JAMA.': [3532], '1987;': [3533], '257:': [3534], '2318–2324.CrossrefMedlineGoogle': [3535], 'Scholar3': [3536], 'Juhan-Vague': [3537], 'I,': [3538], 'Pyke': [3539, 3768, 3810], 'SDM,': [3540, 3769, 3811], 'Alessi': [3541], 'MC,': [3542], 'Jespersen': [3543], 'J,': [3544, 3809, 4020, 4057], 'Haverkate': [3545, 3764, 3812], 'F,': [3546, 3732, 3765, 3813], 'Thompson': [3547, 3766, 3806], 'SG.': [3548], 'Fibrinolytic': [3549], 'death': [3559, 3828], 'pectoris.': [3564, 3833], 'Circulation.': [3565, 3935, 4103], '1996;': [3566, 4077], '94:': [3567], '2057–2063.CrossrefMedlineGoogle': [3568], 'Scholar4': [3569], 'Dinerman': [3570], 'JL,': [3571, 3573], 'Mehta': [3572], 'Saldeen': [3574], 'TG,': [3575], 'Emerson': [3576], 'S,': [3577], 'Wallin': [3578], 'R,': [3579, 3581], 'Davda': [3580], 'Davidson': [3582], 'Increased': [3584], 'neutrophil': [3585], 'elastase': [3586], 'release': [3587], 'pectoris': [3591], 'infarction.': [3595, 3643, 3713], 'J': [3596, 3644, 3685, 3836, 3873, 3903, 3965, 4075], 'Am': [3597, 3684, 4074], 'Coll': [3598], 'Cardiol.': [3599, 3686], '1990;': [3600, 3687], '15:': [3601], '1559–1563.CrossrefMedlineGoogle': [3602], 'Scholar5': [3603], 'Mattila': [3604, 3632], 'KJ,': [3605], 'Valtonen': [3606], 'VV,': [3607], 'Nieminen': [3608], 'MS,': [3609], 'Asikainen': [3610], 'Role': [3612], 'infection': [3614], 'atherosclerosis,': [3620], 'Clin': [3625], 'Infect': [3626], 'Dis.': [3627], '1998;': [3628, 3936, 4104], '26:': [3629], '719–734.CrossrefMedlineGoogle': [3630], 'Scholar6': [3631], 'KJ.': [3633], 'Viral': [3634], 'bacterial': [3636], 'infections': [3637], 'Intern': [3645], '1989;': [3647], '225:': [3648], '293–296.CrossrefMedlineGoogle': [3649], 'Scholar7': [3650], 'Expert': [3652], 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