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2. Familial hypercholesterolaemia: A global call to arms

Author

Vallejo-Vaz, Antonio J., Kondapally Seshasai, Sreenivasa Rao, Cole, Della, Hovingh, G. Kees, Kastelein, John J.P., Mata, Pedro, Raal, Frederick J., Santos, Raul D., Soran, Handrean, Watts, Gerald F., Abifadel, Marianne, Aguilar-Salinas, Carlos A., Akram, Asif, Alnouri, Fahad, Alonso, Rodrigo, Al-Rasadi, Khalid, Banach, Maciej, Bogsrud, Martin P., Bourbon, Mafalda, Bruckert, Eric, Car, Josip, Corral, Pablo, Descamps, Olivier, Dieplinger, Hans, Durst, Ronen, Freiberger, Tomas, Gaspar, Isabel M., Genest, Jaques, Harada-Shiba, Mariko, Jiang, Lixin, Kayikcioglu, Meral, Lam, Carolyn S.P., Latkovskis, Gustavs, Laufs, Ulrich, Liberopoulos, Evangelos, Nilsson, Lennart, Nordestgaard, Børge G., O'Donoghue, John M., Sahebkar, Amirhossein, Schunkert, Heribert, Shehab, Abdulla, Stoll, Mario, Su, Ta-Chen, Susekov, Andrey, Widén, Elisabeth, Catapano, Alberico L., and Ray, Kausik K.

Published
2015
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5. Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

Author

Di Angelantonio, Emanuele, Gao, Pei, Khan, Hassan, Butterworth, Adam S., Wormser, David, Kaptoge, Stephen, Kondapally Seshasai, Sreenivasa Rao, Thompson, Alex, Sarwar, Nadeem, Willeit, Peter, Ridker, Paul M, Barr, Elizabeth L. M., Khaw, Kay-Tee, Psaty, Bruce M., Brenner, Hermann, Balkau, Beverley, Dekker, Jacqueline M., Lawlor, Debbie A., Daimon, Makoto, Willeit, Johann, Njølstad, Inger, Nissinen, Aulikki, Brunner, Eric J., Kuller, Lewis H., Price, Jackie F., Sundström, Johan, Knuiman, Matthew W., Feskens, Edith J. M., Verschuren, W. M. M., Wald, Nicholas, Bakker, Stephan J. L., Whincup, Peter H., Ford, Ian, Goldbourt, Uri, Gómez-de-la-Cámara, Agustín, Gallacher, John, Simons, Leon A., Rosengren, Annika, Sutherland, Susan E., Björkelund, Cecilia, Blazer, Dan G., Wassertheil-Smoller, Sylvia, Onat, Altan, Marín Ibañez, Alejandro, Casiglia, Edoardo, Jukema, Wouter J., Simpson, Lara M., Giampaoli, Simona, Nordestgaard, Børge G., Selmer, Randi, Wennberg, Patrik, Kauhanen, Jussi, Salonen, Jukka T., Dankner, Rachel, Barrett-Connor, Elizabeth, Kavousi, Maryam, Gudnason, Vilmundur, Evans, Denis, Wallace, Robert B., Cushman, Mary, D’Agostino, Ralph B., Sr, Umans, Jason G., Kiyohara, Yutaka, Nakagawa, Hidaeki, Sato, Shinichi, Gillum, Richard F., Folsom, Aaron R., van der Schouw, Yvonne T., Moons, Karel G., Griffin, Simon J., Sattar, Naveed, Wareham, Nicholas J., Selvin, Elizabeth, Thompson, Simon G., and Danesh, John

Published
2014
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8. Association of a Combined Measure of Adherence and Treatment Intensity With Cardiovascular Outcomes in Patients With Atherosclerosis or Other Cardiovascular Risk Factors Treated With Statins and/or Ezetimibe

Author

Khunti, Kamlesh, primary, Danese, Mark D., additional, Kutikova, Lucie, additional, Catterick, David, additional, Sorio-Vilela, Francisco, additional, Gleeson, Michelle, additional, Kondapally Seshasai, Sreenivasa Rao, additional, Brownrigg, Jack, additional, and Ray, Kausik K., additional

Published
2018
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9. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials

Author

Swerdlow, Daniel I., Preiss, David, Kuchenbaecker, Karoline B., Holmes, Michael V., Engmann, Jorgen E. L., Shah, Tina, Sofat, Reecha, Stender, Stefan, Johnson, Paul C. D., Scott, Robert A., Leusink, Maarten, Verweij, Niek, Sharp, Stephen J., Guo, Yiran, Giambartolomei, Claudia, Chung, Christina, Peasey, Anne, Amuzu, Antoinette, Li, KaWah, Palmen, Jutta, Howard, Philip, Cooper, Jackie A., Drenos, Fotios, Lowe, Gordon, Gallacher, John, Stewart, Marlene C. W., Tzoulaki, Ioanna, Buxbaum, Sarah G., van der A, Daphne L., Forouhi, Nita G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Hubacek, Jaroslav A., Kubinova, Ruzena, Baceviciene, Migle, Tamosiunas, Abdonas, Pajak, Andrzej, Topor-Madry, Roman, Stepaniak, Urszula, Malyutina, Sofia, Baldassarre, Damiano, Sennblad, Bengt, Tremoli, Elena, de Faire, Ulf, Veglia, Fabrizio, Ford, Ian, Wouter Jukema, J., Westendorp, Rudi G. J., de Borst, Gert Jan, de Jong, Pim A., Algra, Ale, Spiering, Wilko, H Maitland-van der Zee, Anke H., Klungel, Olaf H., de Boer, Anthonius, Doevendans, Pieter A., Eaton, Charles B., Robinson, Jennifer G., Duggan, David, DIAGRAM Consortium, MAGIC Consortium, InterAct Consortium, Kjekshus, John, Downs, John R., Gotto, Antonio M., Keech, Anthony C., Marchioli, Roberto, Tognoni, Gianni, Sever, Peter S., Poulter, Neil R., Waters, David D., Pedersen, Terje R., Amarenco, Pierre, Nakamura, Haruo, McMurray, John J. V., Lewsey, James D., Chasman, Daniel I., Ridker, Paul M., Maggioni, Aldo P., Tavazzi, Luigi, Ray, Kausik K., Kondapally Seshasai, Sreenivasa Rao, Manson, JoAnn E., Price, Jackie F., Whincup, Peter H., Morris, Richard W., Lawlor, Debbie A., Smith, George Davey, Ben-Shlomo, Yoav, Schreiner, Pamela J., Fornage, Myriam, Siscovick, David S., Cushman, Mary, Kumari, Meena, Wareham, Nick J., Verschuren, W. M. Monique, Redline, Susan, Patel, Sanjay R., Whittaker, John C., Hamsten, Anders, Delaney, Joseph A., Dale, Caroline, Gaunt, Tom R., Wong, Andrew, Kuh, Diana, Hardy, Rebecca, Kathiresan, Sekar, Castillo, Berta A., van der Harst, Pim, Brunner, Eric J., Tybjaerg-Hansen, Anne, Marmot, Michael G., Krauss, Ronald M., Tsai, Michael, Coresh, Josef, Hoogeveen, Ronald C., Psaty, Bruce M., Lange, Leslie A., Hakonarson, Hakon, Dudbridge, Frank, Humphries, Steve E., Talmud, Philippa J., Kivimäki, Mika, Timpson, Nicholas J., Langenberg, Claudia, Asselbergs, Folkert W., Voevoda, Mikhail, Bobak, Martin, Pikhart, Hynek, Wilson, James G., Reiner, Alex P., Keating, Brendan J., Hingorani, Aroon D., Sattar, Naveed, Li, Yun R., Imperial College Healthcare NHS Trust- BRC Funding, National Institute for Health Research, Cardiovascular Centre (CVC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Sharp, Stephen [0000-0003-2375-1440], Forouhi, Nita [0000-0002-5041-248X], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository

Subjects
Male, STATIN THERAPY, Type 2 diabetes, 030204 cardiovascular system & hematology, Gastroenterology, DISEASE, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Medicine, HIGH-DOSE ATORVASTATIN, Randomized Controlled Trials as Topic, RISK, 0303 health sciences, MAGIC Consortium, Articles, 11 Medical And Health Sciences, General Medicine, Middle Aged, 3. Good health, MENDELIAN RANDOMIZATION, Female, Life Sciences & Biomedicine, medicine.medical_specialty, Statin, medicine.drug_class, DIAGRAM Consortium, Placebo, Polymorphism, Single Nucleotide, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Internal medicine, Diabetes mellitus, Humans, Genetic Testing, METAANALYSIS, Aged, 030304 developmental biology, Science & Technology, business.industry, Cholesterol, Body Weight, Cholesterol, HDL, Type 2 Diabetes Mellitus, Cholesterol, LDL, Odds ratio, InterAct Consortium, medicine.disease, R1, PREVENTION, BODY-MASS INDEX, Endocrinology, Diabetes Mellitus, Type 2, chemistry, Hydroxymethylglutaryl CoA Reductases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, LDL CHOLESTEROL, business, ASSOCIATION ANALYSES, Body mass index
Abstract

Background: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.Methods: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis.Findings: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05–0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18–0·43), waist circumference (0·32 cm, 0·16–0·47), plasma insulin concentration (1·62%, 0·53–2·72), and plasma glucose concentration (0·23%, 0·02–0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00–1·05); the rs12916-T allele association was consistent (1·06, 1·03–1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18–1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10–0·38 in all trials; 0·33 kg, 95% CI 0·24–0·42 in placebo or standard care controlled trials and −0·15 kg, 95% CI −0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9–6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06–1·18 in all trials; 1·11, 95% CI 1·03–1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04–1·22 in intensive-dose vs moderate dose trials).Interpretation: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.Funding: The funding sources are cited at the end of the paper.

Published
2015

10. Are statins effective in high-risk primary prevention?

Author

Dentali, Francesco, Guasti, Luigina, Ray, Kausik K., Kondapally Seshasai, Sreenivasa Rao, Jukema, Wouter, and Sattar, Naveed

Subjects
Statins -- Dosage and administration, Cardiovascular diseases -- Prevention, Cardiovascular diseases -- Risk factors, Cardiovascular diseases -- Patient outcomes, Health
Published
2010

12. Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration

Author

Vallejo-Vaz, Antonio J., primary, Akram, Asif, additional, Kondapally Seshasai, Sreenivasa Rao, additional, Cole, Della, additional, Watts, Gerald F., additional, Hovingh, G. Kees, additional, Kastelein, John J.P., additional, Mata, Pedro, additional, Raal, Frederick J., additional, Santos, Raul D., additional, Soran, Handrean, additional, Freiberger, Tomas, additional, Abifadel, Marianne, additional, Aguilar-Salinas, Carlos A., additional, Alnouri, Fahad, additional, Alonso, Rodrigo, additional, Al-Rasadi, Khalid, additional, Banach, Maciej, additional, Bogsrud, Martin P., additional, Bourbon, Mafalda, additional, Bruckert, Eric, additional, Car, Josip, additional, Ceska, Richard, additional, Corral, Pablo, additional, Descamps, Olivier, additional, Dieplinger, Hans, additional, Do, Can T., additional, Durst, Ronen, additional, Ezhov, Marat V., additional, Fras, Zlatko, additional, Gaita, Dan, additional, Gaspar, Isabel M., additional, Genest, Jaques, additional, Harada-Shiba, Mariko, additional, Jiang, Lixin, additional, Kayikcioglu, Meral, additional, Lam, Carolyn S.P., additional, Latkovskis, Gustavs, additional, Laufs, Ulrich, additional, Liberopoulos, Evangelos, additional, Lin, Jie, additional, Lin, Nan, additional, Maher, Vincent, additional, Majano, Nelson, additional, Marais, A. David, additional, März, Winfried, additional, Mirrakhimov, Erkin, additional, Miserez, André R., additional, Mitchenko, Olena, additional, Nawawi, Hapizah, additional, Nilsson, Lennart, additional, Nordestgaard, Børge G., additional, Paragh, György, additional, Petrulioniene, Zaneta, additional, Pojskic, Belma, additional, Reiner, Željko, additional, Sahebkar, Amirhossein, additional, Santos, Lourdes E., additional, Schunkert, Heribert, additional, Shehab, Abdullah, additional, Slimane, M. Naceur, additional, Stoll, Mario, additional, Su, Ta-Chen, additional, Susekov, Andrey, additional, Tilney, Myra, additional, Tomlinson, Brian, additional, Tselepis, Alexandros D., additional, Vohnout, Branislav, additional, Widén, Elisabeth, additional, Yamashita, Shizuya, additional, Catapano, Alberico L., additional, and Ray, Kausik K., additional

Published
2016
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15. Statin pretreatment and risk of in-hospital atrial fibrillation among patients undergoing cardiac surgery: a collaborative meta-analysis of 11 randomized controlled trials.

Author

Patti, Giuseppe, Bennett, Rachel, Kondapally Seshasai, Sreenivasa Rao, Cannon, Christopher P., Cavallari, Ilaria, Chello, Massimo, Nusca, Annunziata, Mega, Simona, Caorsi, Carlos, Spadaccio, Cristiano, Young Keun On, Mannacio, Vito, Berkan, Ocal, Yilmaz, Mehmet B., Katrancioglu, Nurkay, Qiang Ji, Kourliouros, Antonios, Baran, Çağdaş, Pasceri, Vincenzo, and Akar, Ahmet Rüçhan

Abstract

Aims: Statin pretreatment in patients undergoing cardiac surgery is understood to prevent postoperative atrial fibrillation (AF). However, this is based on observational and limited randomized trial evidence, resulting in uncertainty about any genuine anti-arrhythmic benefits of these agents in this setting. We therefore aimed to quantify precisely the association between statin pretreatment and postoperative AF among patients undergoing cardiac surgery. Methods and results: A detailed search of MEDLINE and PubMed databases (1st January 1996 to 31st July 2012) was conducted, followed by a review of the reference lists of published studies and correspondence with trial investigators to obtain individual-participant data for meta-analysis. Evidence was combined across prospective, randomized clinical trials that compared the risk of postoperative AF among individuals randomized to statin pretreatment or placebo/control medication before elective cardiac surgery. Postoperative AF was defined as episodes of AF lasting >=5 min. Overall, 1105 participants from 11 trials were included; of them, 552 received statin therapy preoperatively. Postoperative AF occurred in 19% of these participants when compared with 36% of those not treated with statins (odds ratio 0.41, 95% confidence interval 0.31-0.54, P < 0.00001, using a random-effects model). Atrial fibrillation prevention by statin pretreatment was consistent across different subgroups. Conclusion: Short-term statin pretreatment may reduce the risk of postoperative AF among patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Published
2015
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16. Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy: A Meta-analysis.

Author

Preiss, David, Kondapally Seshasai, Sreenivasa Rao, Welsh, Paul, Murphy, Sabina A., Ho, Jennifer E., Waters, David D., DeMicco, David A., Barter, Philip, Cannon, Christopher P., Sabatine, Marc S., Braunwald, Eugene, Kastelein, John J. P., de Lemos, James A., Blazing, Michael A., Pedersen, Terje R., Tikkanen, Matti J., Sattar, Naveed, and Ray, Kausik K.

Subjects
*STATINS (Cardiovascular agents), *DIABETES risk factors, *CARDIOVASCULAR disease prevention, *CEREBROVASCULAR disease, *MYOCARDIAL revascularization, *CLINICAL trials
Abstract

The article discusses a study which examined whether intensive-dose statin therapy is linked with increased risk of new-onset diabetes compared with moderate-dose statin therapy. It notes that statin therapy is known for reducing cardiovascular events such as stroke and coronary revascularization among those with and without diabetes mellitus. Results showed that a total of 2,749 individuals developed diabetes in five statin trials and 6,684 experienced cardiovascular events. For participants receiving intensive therapy, odds ratios were found to be 1.12 for new-onset diabetes and 0.84 for cardiovascular events. The study also found that there were 155 cardiovascular events needed to treat per year for intensive-dose therapy.

Published
2011
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17. Glycated hemoglobin measurement and prediction of cardiovascular disease

Author

Emerging Risk Factors Collaboration, Di Angelantonio, Emanuele, Gao, Pei, Khan, Hassan, Butterworth, Adam, Wormser, David, Kaptoge, Stephen, Kondapally Seshasai, Sreenivasa Rao, Thompson, Alex, Sarwar, Nadeem, Willeit, Peter, Ridker, Paul M, Barr, Elizabeth LM, Khaw, Kay-Tee, Psaty, Bruce M, Brenner, Hermann, Balkau, Beverley, Dekker, Jacqueline M, Lawlor, Debbie A, Daimon, Makoto, Willeit, Johann, Njølstad, Inger, Nissinen, Aulikki, Brunner, Eric J, Kuller, Lewis H, Price, Jackie F, Sundström, Johan, Knuiman, Matthew W, Feskens, Edith JM, Verschuren, WMM, Wald, Nicholas, Bakker, Stephan JL, Whincup, Peter H, Ford, Ian, Goldbourt, Uri, Gómez-De-La-Cámara, Agustín, Gallacher, John, Simons, Leon A, Rosengren, Annika, Sutherland, Susan E, Björkelund, Cecilia, Blazer, Dan G, Wassertheil-Smoller, Sylvia, Onat, Altan, Marín Ibañez, Alejandro, Casiglia, Edoardo, Jukema, J Wouter, Simpson, Lara M, Giampaoli, Simona, Nordestgaard, Børge G, Selmer, Randi, Wennberg, Patrik, Kauhanen, Jussi, Salonen, Jukka T, Dankner, Rachel, Barrett-Connor, Elizabeth, Kavousi, Maryam, Gudnason, Vilmundur, Evans, Denis, Wallace, Robert B, Cushman, Mary, D'Agostino, Ralph B, Umans, Jason G, Kiyohara, Yutaka, Nakagawa, Hidaeki, Sato, Shinichi, Gillum, Richard F, Folsom, Aaron R, Van Der Schouw, Yvonne T, Moons, Karel G, Griffin, Simon, Sattar, Naveed, Wareham, Nicholas, Selvin, Elizabeth, Thompson, Simon, and Danesh, John

Subjects
Male, Emerging Risk Factors Collaboration, Glycated Hemoglobin A, Cholesterol, HDL, Coronary Disease, Middle Aged, Risk Assessment, 3. Good health, Stroke, C-Reactive Protein, Predictive Value of Tests, Diabetes Mellitus, Humans, Female, Prospective Studies, Aged
Abstract

IMPORTANCE: The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE: To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES: Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (

18. Cardiovascular Management of Adults with Marfan Syndrome.

Author

Isekame Y, Gati S, Aragon-Martin JA, Bastiaenen R, Kondapally Seshasai SR, and Child A

Abstract

Marfan syndrome (MFS) is a disease in which connective tissue becomes weak secondary to fibrillin-1 mutations, resulting in aortic dilatation, aneurysm formation, aortic dissection, aortic regurgitation and mitral valve prolapse. This autosomal dominantly inherited condition, which was first reported in 1895 and was more fully described in 1931, is characterised by abnormal Fibrillin-1 protein (FBN1) (discovered in 1990), which is encoded by the FBN1 gene (reported in 1991). In the 1970s, the life expectancy of people with MFS was 40-50 years, mainly due to increased risk of aortic dissection or heart failure from aortic or mitral regurgitation. However, due to advances in medical and surgical therapy, life expectancy has improved dramatically and is now comparable to that of the general population. We discuss the cardiac manifestations of MFS, the incidence of arrhythmia in this population, the standard of medical care for arrhythmia and valve insufficiency, and a new use of preventive medication to preserve the integrity of the aortic wall in patients with MFS., Competing Interests: Disclosure: The authors have no conflicts of interest to declare.

Published
2016
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