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4 results on '"Durrington PN"'

1. Liver fat measured by MR spectroscopy: Estimate of imprecision and relationship with serum glycerol, caeruloplasmin and non-esterified fatty acids

Author

France, M, Kwok, S, Soran, H, Williams, S, Ho, JH, Adam, S, Canoy, D, Liu, Y, Durrington, PN, France, M, Kwok, S, Soran, H, Williams, S, Ho, JH, Adam, S, Canoy, D, Liu, Y, and Durrington, PN

Abstract

Magnetic resonance spectroscopy (MRS) is a non-invasive method for quantitative estimation of liver fat. Knowledge of its imprecision, which comprises biological variability and measurement error, is required to design therapeutic trials with measurement of change. The role of adipocyte lipolysis in ectopic fat accumulation remains unclear. We examined the relationship between liver fat content and indices of lipolysis, and determine whether lipolysis reflects insulin resistance or metabolic liver disease. Imprecision of measurement of liver fat was estimated from duplicate measurements by MRS at one month intervals. Patients provided fasting blood samples and we examined the correlation of liver fat with indices of insulin resistance, lipolysis and metabolic liver disease using Kendall Tau statistics. The coefficient of variation of liver fat content was 14.8%. Liver fat was positively related to serum insulin (T = 0.48, p = 0.042), homeostasis model assessment (HOMA)-B% (T = −0.48, p = 0.042), and body mass index (BMI) (T = 0.59, p = 0.012); and inversely related to HOMA-S% (T = −0.48, p = 0.042), serum glycerol (T = −0.59, p = 0.014), and serum caeruloplasmin (T = 0.055, p = 0.047). Our estimate of total variability in liver fat content (14.8%) is nearly twice that of the reported procedural variability (8.5%). We found that liver fat content was significantly inversely related to serum glycerol but not to non-esterified fatty acids (NEFA), suggesting progressive suppression of lipolysis. Reduction of caeruloplasmin with increasing liver fat may be a consequence or a cause of hepatic steatosis.

Published
2016

2. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

Author

Postmus, I, Warren, HR, Trompet, S, Arsenault, BJ, Avery, CL, Bis, JC, Chasman, DI, de Keyser, Toke, Deshmukh, HA, Evans, DS, Feng, Q, Li, X, Smit, RAJ, Smith, AV, Sun, F, Taylor, KD, Arnold, AM, Barnes, MR, Barratt, BJ, Betteridge, J, Boekholdt, SM, Boerwinkle, E, Buckley, BM, Chen, YDI, de Craen, AJM, Cummings, SR, Denny, JC, Dube, MP, Durrington, PN, Eiriksdottir, G, Ford, I, Guo, X, Harris, TB, Heckbert, SR, Hofman, Bert, Hovingh, GK, Kastelein, JJP, Launer, LJ, Liu, C-T, Liu, Y, Lumley, T, Mckeigue, PM, Munroe, PB, Neil, A, Nickerson, DA, Nyberg, F, O'Brien, E, O'Donnell, CJ, Post, W, Poulter, N, Vasan, RS, Rice, K, Rich, SS, Rivadeneira, Fernando, Sattar, N, Sever, P, Shaw-Hawkins, S, Shields, DC, Slagboom, PE (Eline), Smith, NL, Smith, JD, Sotoodehnia, N, Stanton, A, Stott, DJ, Stricker, Bruno, Sturmer, T, Uitterlinden, André, Wei, W-Q, Westendorp, RGJ, Whitsel, EA, Wiggins, KL, Wilke, RA, Ballantyne, CM, Colhoun, HM, Cupples, LA, Franco Duran, OH, Gudnason, V, Hitman, G, Palmer, CNA, Psaty, BM, Ridker, PM, Stafford, JM, Stein, CM, Tardif, J-C, Caulfield, MJ, Jukema, JW, Rotter, JI, Krauss, RM, Postmus, I, Warren, HR, Trompet, S, Arsenault, BJ, Avery, CL, Bis, JC, Chasman, DI, de Keyser, Toke, Deshmukh, HA, Evans, DS, Feng, Q, Li, X, Smit, RAJ, Smith, AV, Sun, F, Taylor, KD, Arnold, AM, Barnes, MR, Barratt, BJ, Betteridge, J, Boekholdt, SM, Boerwinkle, E, Buckley, BM, Chen, YDI, de Craen, AJM, Cummings, SR, Denny, JC, Dube, MP, Durrington, PN, Eiriksdottir, G, Ford, I, Guo, X, Harris, TB, Heckbert, SR, Hofman, Bert, Hovingh, GK, Kastelein, JJP, Launer, LJ, Liu, C-T, Liu, Y, Lumley, T, Mckeigue, PM, Munroe, PB, Neil, A, Nickerson, DA, Nyberg, F, O'Brien, E, O'Donnell, CJ, Post, W, Poulter, N, Vasan, RS, Rice, K, Rich, SS, Rivadeneira, Fernando, Sattar, N, Sever, P, Shaw-Hawkins, S, Shields, DC, Slagboom, PE (Eline), Smith, NL, Smith, JD, Sotoodehnia, N, Stanton, A, Stott, DJ, Stricker, Bruno, Sturmer, T, Uitterlinden, André, Wei, W-Q, Westendorp, RGJ, Whitsel, EA, Wiggins, KL, Wilke, RA, Ballantyne, CM, Colhoun, HM, Cupples, LA, Franco Duran, OH, Gudnason, V, Hitman, G, Palmer, CNA, Psaty, BM, Ridker, PM, Stafford, JM, Stein, CM, Tardif, J-C, Caulfield, MJ, Jukema, JW, Rotter, JI, and Krauss, RM

Published
2016

3. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Author

Postmus, I, Trompet, S, Deshmukh, HA, Barnes, MR, Li, XH, Warren, HR, Chasman, DI, Zhou, KX, Arsenault, BJ, Donnelly, LA, Wiggins, KL, Avery, CL, Griffin, P, Feng, QP, Taylor, KD, Li, G, Evans, DS, Smith, AV, de Keyser, Toke, Johnson, AD, de Craen, AJM, Stott, DJ, Buckley, BM, Ford, I, Westendorp, RGJ, Slagboom, PE (Eline), Sattar, N, Munroe, PB, Sever, P, Poulter, N, Stanton, A, Shields, DC, O'Brien, E, Shaw-Hawkins, S, Chen, YDI, Nickerson, DA, Smith, JD, Dube, MP, Boekholdt, SM, Hovingh, GK, Kastelein, JJP, Mckeigue, PM, Betteridge, J, Neil, A, Durrington, PN, Doney, A, Carr, F, Morris, A, McCarthy, MI, Groop, L, Ahlqvist, E, Bis, JC, Rice, K, Smith, NL, Lumley, T, Whitsel, EA, Sturmer, T, Boerwinkle, E, Ngwa, JS, O'Donnell, CJ, Vasan, RS, Wei, WQ, Wilke, RA, Liu, CT, Sun, FG, Guo, XQ, Heckbert, SR, Post, W, Sotoodehnia, N, Arnold, AM, Stafford, JM, Ding, JZ (Jing Zhong), Herrington, DM, Kritchevsky, SB, Eiriksdottir, G, Launer, LJ (Lenore), Harris, TB, Chu, AY, Giulianini, F, MacFadyen, JG, Barratt, BJ, Nyberg, F, Stricker, Bruno, Uitterlinden, André, Hofman, Bert, Rivadeneira, Fernando, Emilsson, V, Franco Duran, OH, Ridker, PM, Gudnason, V, Liu, YM, Denny, JC, Ballantyne, CM, Rotter, JI, Cupples, LA, Psaty, BM, Palmer, CNA, Tardif, JC, Colhoun, HM, Hitman, G, Krauss, RM, Jukema, JW, Caulfield, MJ, Postmus, I, Trompet, S, Deshmukh, HA, Barnes, MR, Li, XH, Warren, HR, Chasman, DI, Zhou, KX, Arsenault, BJ, Donnelly, LA, Wiggins, KL, Avery, CL, Griffin, P, Feng, QP, Taylor, KD, Li, G, Evans, DS, Smith, AV, de Keyser, Toke, Johnson, AD, de Craen, AJM, Stott, DJ, Buckley, BM, Ford, I, Westendorp, RGJ, Slagboom, PE (Eline), Sattar, N, Munroe, PB, Sever, P, Poulter, N, Stanton, A, Shields, DC, O'Brien, E, Shaw-Hawkins, S, Chen, YDI, Nickerson, DA, Smith, JD, Dube, MP, Boekholdt, SM, Hovingh, GK, Kastelein, JJP, Mckeigue, PM, Betteridge, J, Neil, A, Durrington, PN, Doney, A, Carr, F, Morris, A, McCarthy, MI, Groop, L, Ahlqvist, E, Bis, JC, Rice, K, Smith, NL, Lumley, T, Whitsel, EA, Sturmer, T, Boerwinkle, E, Ngwa, JS, O'Donnell, CJ, Vasan, RS, Wei, WQ, Wilke, RA, Liu, CT, Sun, FG, Guo, XQ, Heckbert, SR, Post, W, Sotoodehnia, N, Arnold, AM, Stafford, JM, Ding, JZ (Jing Zhong), Herrington, DM, Kritchevsky, SB, Eiriksdottir, G, Launer, LJ (Lenore), Harris, TB, Chu, AY, Giulianini, F, MacFadyen, JG, Barratt, BJ, Nyberg, F, Stricker, Bruno, Uitterlinden, André, Hofman, Bert, Rivadeneira, Fernando, Emilsson, V, Franco Duran, OH, Ridker, PM, Gudnason, V, Liu, YM, Denny, JC, Ballantyne, CM, Rotter, JI, Cupples, LA, Psaty, BM, Palmer, CNA, Tardif, JC, Colhoun, HM, Hitman, G, Krauss, RM, Jukema, JW, and Caulfield, MJ

Abstract

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.

Published
2014

4. Lack of effect of lowering LDL cholesterol on cancer: Meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

Author

Emberson, JR, Kearney, PM, Blackwell, L, Newman, C, Reith, C, Bhala, N, Holland, L, Peto, R, Keech, A, Collins, R, Simes, J, Baigent, C, De Lemos, J, Braunwald, E, Blazing, M, Murphy, S, Downs, JR, Gotto, A, Clearfield, M, Holdaas, H, Gordon, D, Davis, B, Koren, M, Dahlof, B, Poulter, N, Sever, P, Knopp, RH, Fellström, B, Jardine, A, Schmieder, R, Zannad, F, Goldbourt, U, Kaplinsky, E, Colhoun, HM, Betteridge, DJ, Durrington, PN, Hitman, GA, Fuller, J, Neil, A, Wanner, C, Krane, V, Sacks, F, Moyé, L, Pfeffer, M, Hawkins, CM, Kjekshus, J, Wedel, H, Wikstrand, J, Tavazzi, L, Maggioni, A, Marchioli, R, Tognoni, G, Franzosi, MG, Armitage, J, Parish, S, Sleight, P, Pedersen, TR, Ridker, PM, MacMahon, S, Marschner, I, Tonkin, A, Shaw, J, Serruys, PW, Nakamura, H, Knatterud, G, Furberg, C, Byington, R, Macfarlane, P, Cobbe, S, Ford, I, Murphy, M, Blauw, GJ, Packard, C, Shepherd, J, Wilhelmsen, L, Cannon, C, Bowman, L, La Rosa, J, Flather, M, Kastelein, J, Shear, C, Tobert, J, Varigos, J, White, H, Yusuf, S, Baxter, A, Barnes, EH, Buck, G, Herrington, WG, Kirby, A, Lewis, DA, Mellies, M, McGovern, M, Barclay, J, Belder, R, Mitchell, Y, Musliner, T, Ansquer, JC, Llewellyn, M, Bortolini, M, Emberson, JR, Kearney, PM, Blackwell, L, Newman, C, Reith, C, Bhala, N, Holland, L, Peto, R, Keech, A, Collins, R, Simes, J, Baigent, C, De Lemos, J, Braunwald, E, Blazing, M, Murphy, S, Downs, JR, Gotto, A, Clearfield, M, Holdaas, H, Gordon, D, Davis, B, Koren, M, Dahlof, B, Poulter, N, Sever, P, Knopp, RH, Fellström, B, Jardine, A, Schmieder, R, Zannad, F, Goldbourt, U, Kaplinsky, E, Colhoun, HM, Betteridge, DJ, Durrington, PN, Hitman, GA, Fuller, J, Neil, A, Wanner, C, Krane, V, Sacks, F, Moyé, L, Pfeffer, M, Hawkins, CM, Kjekshus, J, Wedel, H, Wikstrand, J, Tavazzi, L, Maggioni, A, Marchioli, R, Tognoni, G, Franzosi, MG, Armitage, J, Parish, S, Sleight, P, Pedersen, TR, Ridker, PM, MacMahon, S, Marschner, I, Tonkin, A, Shaw, J, Serruys, PW, Nakamura, H, Knatterud, G, Furberg, C, Byington, R, Macfarlane, P, Cobbe, S, Ford, I, Murphy, M, Blauw, GJ, Packard, C, Shepherd, J, Wilhelmsen, L, Cannon, C, Bowman, L, La Rosa, J, Flather, M, Kastelein, J, Shear, C, Tobert, J, Varigos, J, White, H, Yusuf, S, Baxter, A, Barnes, EH, Buck, G, Herrington, WG, Kirby, A, Lewis, DA, Mellies, M, McGovern, M, Barclay, J, Belder, R, Mitchell, Y, Musliner, T, Ansquer, JC, Llewellyn, M, and Bortolini, M

Abstract

© 2012 CTT Collaboration. Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials. Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93-1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93-1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82-1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76-1.10]). Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).

Published
2012

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