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"fuente" => "Adapted from the consensus document developed by the American Diabetes Association and the European Association for the Study of Diabetes (ADA/EADS). <span class="elsevierStyleItalic">Source</span>: Inzucchi et al.<span class="elsevierStyleSup">4</span>"
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"textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Hypertension</span><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleSmallCaps">C</span>. Suárez Fernández</span></p><p id="par0010" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Vascular Risk Unit, Department of Internal Medicine, University Hospital La Princesa, Madrid, Spain</span></p><p id="par0015" class="elsevierStylePara elsevierViewall">The purpose of this article is to highlight the most important developments published in the field of arterial hypertension (AHT) during 2012 and the first quarter of 2013. Issues related to the epidemiology and the treatment of AHT with clinical relevance have been selected.</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">The evolution of arterial hypertension management in Spain</span><p id="par0020" class="elsevierStylePara elsevierViewall">The PRESCAP<span class="elsevierStyleSup">1</span> study showed a favorable evolution of AHT management in primary care visits at the national level, going from a level of control (BP <140/90<span class="elsevierStyleHsp" style=""></span>mmHg) of 36.1% in 2002 to 41.4% in 2006 and 46.3% in 2010. This improvement is mainly attributed to the greater use of combination therapy (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). A recent publication<span class="elsevierStyleSup">2</span> that was not just in favor of the use of combination therapy but also supported its introduction since the beginning showed how starting with combined therapy compared with monotherapy achieved 40.3% versus 32.6% control at 6 months. This translates into a reduced risk of 23% for experiencing a cardiovascular (CV) event or death (hazard ratio: 0.77 [95% CI: 0.61–0.96]; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.0223) in the case of the controls. Initial combination therapy is associated with a reduction in the risk of experiencing a CV event or death (incidence ratio: 0.66 [95% CI: 0.52–0.84]; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.0008).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Prognostic markers</span><p id="par0025" class="elsevierStylePara elsevierViewall">AHT in pregnancy. Over the course of this period, various studies have been published, such as the cohort study of Finnish women followed-up for almost 40 years.<span class="elsevierStyleSup">3</span> The study showed how the development of AHT, in any of its modalities (chronic AHT, gestational AHT, preeclampsia–eclampsia) during pregnancy is associated with a higher risk of developing CV disease, chronic kidney disease and diabetes mellitus.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The hypertensive response to moderate exercise, such as exercise stress tests, defined as an SBP<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>210<span class="elsevierStyleHsp" style=""></span>mmHg in men or ≥190<span class="elsevierStyleHsp" style=""></span>mmHg in women, or a DBP<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>110<span class="elsevierStyleHsp" style=""></span>mmHg during the test, is an independent predictor of CV morbidity and mortality (a 36% increase in CV events and mortality compared with subjects with no hypertensive response).</p><p id="par0035" class="elsevierStylePara elsevierViewall">Each SBP increase of 10<span class="elsevierStyleHsp" style=""></span>mmHg is associated with a 4% increase in the risk of CV events (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.02). These data were obtained from a meta-analysis and systematic review based on 12 cohort studies (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>46,314), with a mean follow-up of 15.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4 years.<span class="elsevierStyleSup">4</span> Its presence requires the performing of OBPM or SMBP, given the high prevalence of masked AHT (as high as 58%), as well as an echocardiogram, due to the high frequency of left ventricular hypertrophy.<span class="elsevierStyleSup">5</span> Preliminary data suggest a favorable effect of low-dose spironolactone on both BP and on morphological parameters.<span class="elsevierStyleSup">6</span></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Transthoracic Bioimpedance (HOTMAN<span class="elsevierStyleSup">®</span>)</span><p id="par0040" class="elsevierStylePara elsevierViewall">This technique has been proposed for improving the management of AHT. Although there are still no published articles on the subject, experiences have been presented at conferences and studies are underway (ClinicalTrials.gov Identifier: <a id="intr0005" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/NCT01482364">NCT01482364</a>; ClinicalTrials.gov Identifier: <a id="intr0010" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/NCT01673516">NCT01673516</a>) whose initial results show the usefulness of this technique and the considerable contribution of volume overload to the development and maintenance of AHT.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Treatment</span><p id="par0045" class="elsevierStylePara elsevierViewall">The new European Guidelines on Cardiovascular Disease Prevention<span class="elsevierStyleSup">7</span> reinforced the European AHT recommendations of 2009 without providing any new relevant data. With regard to lifestyle, there are publications that show the beneficial effect of cocoa consumption on BP,<span class="elsevierStyleSup">8</span> caloric intake mainly in the early hours of the day<span class="elsevierStyleSup">9</span> and the existence of a U curve in terms of the hours of sleep and the risk of developing AHT. The denervation of renal arteries for the treatment of resistant AHT is, probably, the issue that has gained the greatest interest during this period. After the publication of the follow-up for the Symplicity HTN-1 and HTN-2 studies, various guidelines and national consensus were developed that specify the most widely accepted criteria for its indication:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0050" class="elsevierStylePara elsevierViewall">Clinical SBP: ≥160<span class="elsevierStyleHsp" style=""></span>mmHg (≥150<span class="elsevierStyleHsp" style=""></span>mmHg in type 2 diabetes).</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0055" class="elsevierStylePara elsevierViewall">OBPM: mean SBP: ≥150<span class="elsevierStyleHsp" style=""></span>mmHg (≥140<span class="elsevierStyleHsp" style=""></span>mmHg in patients with diabetes).</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0060" class="elsevierStylePara elsevierViewall">≥3 antihypertensive agents.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0065" class="elsevierStylePara elsevierViewall">Secondary AHT ruled out.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">•</span><p id="par0070" class="elsevierStylePara elsevierViewall">Poor compliance ruled out.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">•</span><p id="par0075" class="elsevierStylePara elsevierViewall">Favorable renal artery anatomy.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">•</span><p id="par0080" class="elsevierStylePara elsevierViewall">Patient informed consent.</p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall">This technique, in addition to providing a significant and sustained reduction in BP, has shown additional benefits such as improved left ventricular hypertrophy, cardiac function, resistance to insulin and metabolic control and a reduction in the apnea index.</p><p id="par0090" class="elsevierStylePara elsevierViewall">The first clinical series in Spain has been published.<span class="elsevierStyleSup">10</span> Of the 197 patients with resistant AHT demonstrated with OBPM and after ruling out patients with pseudorefractory AHT and those who respond to spironolactone, only 15% were candidates for renal denervation (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The results in these 29 patients at 3 months were favorable in terms of the mean reduction in BP achieved, although only 1 of every 10 patients could have all antihypertensive drugs withdrawn (the mean number of drugs prescribed decreased with the procedure from 4.3 to 3.2).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">References</span><p id="par0095" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">1.</span><p id="par0100" class="elsevierStylePara elsevierViewall">Llisterri JL, Rodriguez-Roca GC, Escobar C, Alonso-Moreno FJ, Prieto MA, Barrios <span class="elsevierStyleSmallCaps">V</span>, et al.; Working Group of Arterial Hypertension of the Spanish Society of Primary Care Physicians Group HTASEMERGEN; PRESCAP 2010 investigators. Treatment and blood pressure control in Spain during 2002–2010. J Hypertens. 2012;30:2425–31.</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">2.</span><p id="par0105" class="elsevierStylePara elsevierViewall">Gradman AH, Parisé H, Lefebvre P, Falvey H, Lafeuille MH, Duh MS. Initial combination therapy reduces the risk of cardiovascular events in hypertensive patients: a matched cohort study. Hypertension. 2013;61:309–18.</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">3.</span><p id="par0110" class="elsevierStylePara elsevierViewall">Männistö T, Mendola P, Vääräsmäki M, Järvelin MR, Hartikainen AL, Pouta A, et al. Elevated blood pressure in pregnancy and subsequent chronic disease risk. Circulation. 2013;127:681–90.</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">4.</span><p id="par0115" class="elsevierStylePara elsevierViewall">Schultz MG, Otahal P, Cleland VJ, Blizzard L, Marwick TH, Sharman JE. Exercise-induced hypertension, cardiovascular events, and mortality in patients undergoing exercise stress testing: A systematic review and meta-analysis. Am J Hypertens. 2013;26:357–66.</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">5.</span><p id="par0120" class="elsevierStylePara elsevierViewall">Sharman JE, Hare JL, Thomas S, Davies JE, Leano R, Jenkins C, et al. Association of masked hypertension and left ventricular remodeling with the hypertensive response to exercise. Am J Hypertens. 2011;24:898–903.</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">6.</span><p id="par0125" class="elsevierStylePara elsevierViewall">Hare JL, Sharman JE, Leano R, Jenkins C, Wright L, Marwick TH. Impact of spironolactone on vascular, myocardial, and functional parameters in untreated patients with a hypertensive response to exercise. Am J Hypertens. 2013;26:691–9.</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">7.</span><p id="par0130" class="elsevierStylePara elsevierViewall">Perk J, de Backer G, Gohlke H, Graham <span class="elsevierStyleSmallCaps">I</span>, Reiner Z, Verschuren WM, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur J Prev Cardiol. 2012;19:585–667.</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">8.</span><p id="par0135" class="elsevierStylePara elsevierViewall">Ried K, Sullivan TR, Fakler P, Frank OR, Stocks NP. Effect of cocoa on blood pressure. Cochrane Database Syst Rev. 2012;8:CD008893.</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">9.</span><p id="par0140" class="elsevierStylePara elsevierViewall">Almoosawi S, Prynne CJ, Hardy R, Stephen AM. Time-of-day of energy intake: association with hypertension and blood pressure 10 years later in the 1946 British Birth Cohort. J Hypertens. 2013;31:882–92.</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">10.</span><p id="par0145" class="elsevierStylePara elsevierViewall">Fontenla A, García-Donaire JA, Hernández F, Segura J, Salgado R, Cerezo C, et al. Manejo de la hipertensión resistente en una unidad multidisciplinaria de denervación renal: protocolo y resultados. Rev Esp Cardiol. 2013;66:364–70.</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antithrombosis</span><p id="par0150" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">F. García-Bragado Dalmau</span></p><p id="par0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Department of Internal Medicine, University Hospital Dr. Josep Trueta, Girona, Spain</span></p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Venous thromboembolism prophylaxis</span><p id="par0160" class="elsevierStylePara elsevierViewall">Semuloparin is a very low-molecular-weight heparin with drug characteristics that may represent an advance in the prophylaxis of venous thromboembolism (VTE). The SAVE<span class="elsevierStyleSup">1</span> program comparatively assessed the results of semuloparin with those of enoxaparin in 3 clinical trials in patients who underwent elective implantation of a knee prosthesis, a hip prosthesis or who underwent hip fracture surgery, respectively. The semuloparin only showed superiority versus enoxaparin in hip replacements (OR: 0.54; 95% CI: 0.38–0.74; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.0003). The safety profiles were similar.</p><p id="par0165" class="elsevierStylePara elsevierViewall">For patients undergoing outpatient chemotherapy for solid neoplasms, semuloparin lowered the incidence of VTE (HR: 0.36; 95% CI: 0.21–0.60; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001; NNT: 46) when compared with placebo, with no significant differences in the rate of clinically significant hemorrhaging or in the rate of major hemorrhaging.<span class="elsevierStyleSup">2</span></p><p id="par0170" class="elsevierStylePara elsevierViewall">A phase II trial showed promising results for patients undergoing chemotherapy for cancer when using apixaban compared with placebo; subsequent phase III trials elected to use dosages of 5<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h.<span class="elsevierStyleSup">3</span></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Treatment of venous thromboembolism</span><p id="par0175" class="elsevierStylePara elsevierViewall">EINSTEIN–EP<span class="elsevierStyleSup">4</span> was a noninferiority, randomized, open, event-driven trial that randomized 4833 patients with pulmonary embolism (PE), with or without deep vein thrombosis, to receive rivaroxaban 15<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h for 21 days, followed by 20<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h for 3, 6 or 12 months, compared with enoxaparin and vitamin K antagonists. Compared with conventional therapy, rivaroxaban was noninferior. There were also no significant differences in the primary efficacy variable; however, there was a highly significant reduction in the incidence of major hemorrhaging (HR: 0.49; 95% CI: 0.31–0.79; NNT: 90).</p><p id="par0180" class="elsevierStylePara elsevierViewall">Another long-acting anti-Xa, idrabiotaparinux, was assessed in PE in the CASSIOPEA study,<span class="elsevierStyleSup">5</span> a noninferiority, randomized, double-blind, double-simulation study that assigned patients to an anticoagulation strategy with enoxaparin for 5–7 days, followed by weekly treatment with subcutaneous warfarin or idrabiotaparinux. Idrabiotaparinux was noninferior compared with conventional treatment and had a lower incidence of hemorrhaging.</p><p id="par0185" class="elsevierStylePara elsevierViewall">We would like to highlight 2 studies that assessed thrombolysis in patients with PE. The first study showed that the administration of 50<span class="elsevierStyleHsp" style=""></span>mg doses of tPA (50% less than usual, which the authors called “safe thrombolysis”), followed by anticoagulation was as safe and effective as anticoagulation alone but with a lower incidence of pulmonary hypertension, although the results should be taken with a certain amount of caution since the incidence of pulmonary hypertension in the control arm was disproportionately high.<span class="elsevierStyleSup">6</span> In the second study (PEITHO), tenecteplase combined with heparin was compared against placebo combined with heparin in normotensive patients with PE and right ventricle dysfunction. The thrombolysis lowered the incidence of the composite variable of all-cause death and circulatory collapse in the following 7 days (2.6% vs. 5.6%; RRR: 56%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.015), at the cost of a higher rate of hemorrhaging (6.5% vs. 1.5%). The best risk-benefit profile was for patients younger than 75 years of age.<span class="elsevierStyleSup">7</span></p><p id="par0190" class="elsevierStylePara elsevierViewall">The catheter-directed thrombolysis showed improvement of the recanalization and reduced the incidence of post-thrombotic syndrome in patients with iliofemoral deep vein thrombosis in the CaVenT trial.<span class="elsevierStyleSup">8</span></p><p id="par0195" class="elsevierStylePara elsevierViewall">The time required for maintaining the anticoagulant therapy is not well specified. For patients with VTE who had already been anticoagulated with vitamin K antagonists or apixaban for 6 or 12 months, extending apixaban therapy for 12 months (at dosages of either 5<span class="elsevierStyleHsp" style=""></span>mg/day or 2.5<span class="elsevierStyleHsp" style=""></span>mg/day) decreased the risk of recurrence without increasing the risk of major hemorrhaging when compared with placebo.<span class="elsevierStyleSup">9</span> The efficacy of the expanded therapy was also observed in studies performed with dabigatran. For patients who had already received at least 3 months of anticoagulation, continuing with 150<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h of dabigatran lowered the incidence of recurrence when compared with the placebo group, although major or clinically relevant hemorrhaging was more common. When the extended dabigatran therapy was compared with warfarin, dabigatran was not inferior in preventing recurrences, and there was less major or clinically relevant hemorrhaging.<span class="elsevierStyleSup">10</span></p><p id="par0200" class="elsevierStylePara elsevierViewall">New studies have shown that acetylsalicylic acid (ASA) prevents the recurrence of VTE and have indicated its role in secondary prophylaxis. The WARFASA study<span class="elsevierStyleSup">11</span> showed that, for patients with idiopathic VTE who had been treated with anticoagulant therapy for 6–18 months, ASA at dosages of 100<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h for a median of 24.6 months significantly lowered recurrence (HR: 0.58; 95% CI: 0.36–0.93; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.02) without increasing major hemorrhaging when compared with placebo. In a similar scenario (the ASPIRE study<span class="elsevierStyleSup">12</span>), ASA lowered the recurrence of VTE but without reaching statistical significance, although it significantly reduced the rate of major vascular events. The authors of the study performed an analysis of the grouped populations of WARFASA and ASPIRE; the results showed that ASA significantly reduces the recurrence of both VTE and major vascular events, without increasing major hemorrhaging.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Secondary prophylaxis in acute coronary syndrome</span><p id="par0205" class="elsevierStylePara elsevierViewall">The results of the ATLAS ACS 2–TIMI 51 study<span class="elsevierStyleSup">13</span> showed that for patients with a recent acute coronary syndrome (ACS), rivaroxaban at dosages of 2.5<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h and 5<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h was more effective than placebo in reducing the incidence of the composite variable of cardiovascular death, acute myocardial infarction and stroke (HR: 0.84; 95% CI: 0.74–0.96; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.008; NNT: 56). Mortality was lower with the dosage of 2.5<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h. Rivaroxaban increased the risk of major and intracranial hemorrhaging but not the risk of lethal hemorrhaging. The results were similar in the subgroup of patients with ACS with ST-elevation.<span class="elsevierStyleSup">14</span> These results have prompted the European Medicines Agency to issue a positive opinion on the dosage of 2.5<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h for rivaroxaban for the ACS indication.</p><p id="par0210" class="elsevierStylePara elsevierViewall">Although prasugrel can provide more benefits than clopidogrel for patients who undergo percutaneous coronary surgery, a recent comparative study of both antiplatelet agents in patients with ACS without ST-elevation who did not undergo angioplasty found no differences between the 2 groups in any of the analyzed variables.<span class="elsevierStyleSup">15</span></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Secondary prophylaxis after an atherothrombotic event</span><p id="par0215" class="elsevierStylePara elsevierViewall">A large clinical trial on patients with recent histories of acute myocardial infarction, ischemic stroke or peripheral arterial disease found that vorapaxar, when compared with placebo, lowered the risk of CV death and ischemic event, but at the cost of major hemorrhaging that was difficult to accept.<span class="elsevierStyleSup">16</span> These results and prior experience dampen the initial expectations placed on a drug that inhibits platelets by a mechanism different from that of standard antiplatelet agents.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Primary prophylaxis in heart failure in sinus rhythm</span><p id="par0220" class="elsevierStylePara elsevierViewall">The WARCEF study<span class="elsevierStyleSup">17</span> showed that, in patients with systolic heart failure in sinus rhythm, there were no differences between the efficacy of warfarin and ASA. The rate of ischemic stroke was lower with warfarin, but at the cost of a higher rate of major hemorrhaging.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Secondary prophylaxis after lacunar infarction</span><p id="par0225" class="elsevierStylePara elsevierViewall">The SPS3 study<span class="elsevierStyleSup">18</span> showed that adding clopidogrel to ASA in patients with a recent lacunar infarction does not decrease recurrence and increases major hemorrhaging and mortality, which represented a new failure for this modality of double antiplatelet therapy in patients with stroke.</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">References</span><p id="par0230" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">1.</span><p id="par0235" class="elsevierStylePara elsevierViewall">Lassen MR, Fisher W, Mouret P, Agnelli G, George D, Kakkar A, et al. Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: results from three randomized clinical trials, SAVE–HIP 1, SAVE–HIP 2 and SAVE–KNEE. J Thromb Haemost. 2012;10:822–32.</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">2.</span><p id="par0240" class="elsevierStylePara elsevierViewall">Agnelli G, George DJ, Kakkar AK, Fisher W, Lassen MR, Mismetti P, et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med. 2012;366:601–9.</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">3.</span><p id="par0245" class="elsevierStylePara elsevierViewall">Levine MN, Gu C, Liebman HA, Escalante CP, Solymoss S, Deitchman D, et al. A randomized phase <span class="elsevierStyleSmallCaps">ii</span> trial of apixaban for the prevention of thromboembolism in patients with metastatic cáncer. J Thromb Haemost. 2012;10:807–14.</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">4.</span><p id="par0250" class="elsevierStylePara elsevierViewall">Büller HR, Prins MH, Lensing AWA, Decousus H, Jacobson BF, Minar E, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287–97.</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">5.</span><p id="par0255" class="elsevierStylePara elsevierViewall">Büller HR, Gallus AS, Pillion G, Prins MH, Raskob GE. Enoxaparin followed by once-weekly idrabiotaparinux versus enoxaparin plus warfarin for patients with acute symptomatic pulmonary embolism: a randomized, double-blind, double-dummy, non-inferiority trial. Lancet. 2012;379:123–9.</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">6.</span><p id="par0260" class="elsevierStylePara elsevierViewall">Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M. Moderate pulmonary embolism treated with thrombolysis (from the MOPETT Trial). Am J Cardiol. 2013;111:273–7.</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">7.</span><p id="par0265" class="elsevierStylePara elsevierViewall">Available at <a id="intr0015" class="elsevierStyleInterRef" href="http://www.theheart.org/article/1517447.do">http://www.theheart.org/article/1517447.do</a> [accessed 12.03.13].</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">8.</span><p id="par0270" class="elsevierStylePara elsevierViewall">Enden T, Haig Y, Klow N-E, Slagsvold C-E, Sandvik L, Ghanima W, et al. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomized controlled trial. Lancet 2012;379:31–8.</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">9.</span><p id="par0275" class="elsevierStylePara elsevierViewall">Agnelli G, Büller HR, Cohen A, Curto M, Gallus AS, Johnson M, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368:699–708.</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">10.</span><p id="par0280" class="elsevierStylePara elsevierViewall">Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368:709–18.</p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">11.</span><p id="par0285" class="elsevierStylePara elsevierViewall">Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012;366:1959–67.</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">12.</span><p id="par0290" class="elsevierStylePara elsevierViewall">Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012;367:1979–87.</p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">13.</span><p id="par0295" class="elsevierStylePara elsevierViewall">Mega JL, Braunwald E, Wiviott SD, Bassand JP, Bhatt DL, Bode C, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366:9–19.</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">14.</span><p id="par0300" class="elsevierStylePara elsevierViewall">Mega JL, Braunwald E, Murphy A, Plotnikov A, Burton P, Kiss RG, et al. Rivaroxaban in patients stabilized after a ST–elevation myocardial infarction: Results from the ATLAS ACS 2–TIMI 51 Trial. J Am Coll Cardiol. 2013;61:1853–9.</p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">15.</span><p id="par0305" class="elsevierStylePara elsevierViewall">Roe, MT, Armstrong PW, Fox KAA, White HD, Prabhakaran D, Goodman SG, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med. 2012;367:1297–309.</p></li><li class="elsevierStyleListItem" id="lsti0165"><span class="elsevierStyleLabel">16.</span><p id="par0310" class="elsevierStylePara elsevierViewall">Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Fish MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366:1404–13.</p></li><li class="elsevierStyleListItem" id="lsti0170"><span class="elsevierStyleLabel">17.</span><p id="par0315" class="elsevierStylePara elsevierViewall">Homma S, Thompson JLP, Pullicino PM, Levin B, Freudenberger RS, Teerlink JR, et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012;366:1859–69.</p></li><li class="elsevierStyleListItem" id="lsti0175"><span class="elsevierStyleLabel">18.</span><p id="par0320" class="elsevierStylePara elsevierViewall">The SPS3 Investigators. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med. 2012;367:817–25.</p></li></ul></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Lipids and nutrition</span><p id="par0325" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">J.M. Mostaza Prieto</span></p><p id="par0330" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Lipids and Risk Vascular Unit, Hospital Carlos III, Madrid, Spain</span></p><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Lipid-lowering treatment</span><p id="par0335" class="elsevierStylePara elsevierViewall">Last year, only 2 clinical trials on the morbidity and mortality of lipid-lowering agents were presented. Both studies have helped stop the clinical development of the drugs evaluated.</p><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Nicotinic acid and laropiprant</span><p id="par0340" class="elsevierStylePara elsevierViewall">Nicotinic acid is a drug than that had shown favorable changes in lipids and was associated with significant reductions in the rate of cardiovascular complications and death. However, its side effects and the arrival of statins had relegated its use to a small number of individuals. It seemed necessary to demonstrate that its favorable effects on morbidity and mortality continued in patients treated with statins. With this objective in mind, the HPS2-THRIVE study was developed.<span class="elsevierStyleSup">1</span> More than 25,000 subjects at high risk in optimal therapy with statins (mean LDL-cholesterol level of 63<span class="elsevierStyleHsp" style=""></span>mg/dl) were randomly assigned to treatment with nicotinic acid combined with laropiprant (a prostaglandin-receptor inhibitor that reduces the intensity of flushing) or placebo. After a median follow-up of 3.9 years, there were no observed differences in the rate of cardiovascular complications between the two groups, with a greater rate of adverse effects in the nicotinic acid group. These results have led to the discontinued marketing of the nicotinic acid/laropiprant combination.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Dalcetrapib</span><p id="par0345" class="elsevierStylePara elsevierViewall">The cholesteryl ester transfer protein [CETP] inhibitors are a group of drugs that block a key enzyme in the reverse transport of cholesterol, raising the plasma concentration of HDL-cholesterol. The first of these drugs, torcetrapib, was withdrawn from the market for causing an increase in mortality, apparently as a result of the activation of the renin–angiotensin system. The second of these drugs that entered the clinical development phase was dalcetrapib. This year, the study dal-OUTCOMES was published,<span class="elsevierStyleSup">2</span> a study on the morbidity and mortality in patients with acute coronary syndrome. Participants who were treated with dalcetrapib experienced a 30% increase in their HDL-cholesterol concentration, despite not lowering their rate of cardiovascular complications. These data have led to the cessation of clinical development of this drug.</p><p id="par0350" class="elsevierStylePara elsevierViewall">Currently, 2 CETP inhibitors, anacetrapib and evacetrapib, continue in development. Both drugs increase HDL-cholesterol levels by more than 100% and reduce LDL-cholesterol levels by 35% to 40%. We await morbidity and mortality data to determine whether these drugs will reach the marketing phase.</p><p id="par0355" class="elsevierStylePara elsevierViewall">In addition to the CETP inhibitors, the only lipid-lowering agents that currently are in phase III of clinical development are the PCSK9 inhibitors.</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">PCSK9 inhibitors</span><p id="par0360" class="elsevierStylePara elsevierViewall">The LDL receptor plays a fundamental role in the metabolism of LDL. After the uptake of a circulating LDL particle, the LDL-receptor complex is internalized (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The LDL particle is hydrolyzed in the cytoplasm and the receptor is recycled toward the cell surface to capture new LDL particles. The larger the number of these receptors, the lower the amount of LDL-cholesterol in the blood. PCSK9 is a circulating protein that binds to the LDL receptor and prevents its internalization and recycling. Therefore, high concentrations of this protein reduce the availability of LDL receptors and increase the plasma concentration of LDL. In contrast, blocking these proteins with neutralizing antibodies allows for the greater availability of surface receptors to capture LDL molecules and thereby reduces plasma cholesterol levels. Last year, numerous efficacy studies with several of these drugs were published, which demonstrated that its subcutaneous administration every 2 or 4 weeks reduces LDL-cholesterol levels by 40–70% beyond that already achieved with statins.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Vitamins and antioxidants</span><p id="par0365" class="elsevierStylePara elsevierViewall">The number of studies that have assessed the efficacy of vitamin and antioxidant supplements on the rate of cardiovascular events has fallen in recent years as a result of continuously negative results. A study was published this year that once again demonstrated the ineffectiveness of a multivitamin preparation in reducing cardiovascular complications.<span class="elsevierStyleSup">3</span> As a corollary to the studies performed to date, this year various meta-analyses have been published that demonstrate that neither omega-3 fatty acid supplements<span class="elsevierStyleSup">4</span> nor vitamins or antioxidants<span class="elsevierStyleSup">5</span> are effective for reducing the rate of cardiovascular complications or mortality.</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Diet and exercise</span><p id="par0370" class="elsevierStylePara elsevierViewall">The efficacy of statins seemed to eclipse dietary and general health measures. It is of importance therefore that 2 recent studies demonstrated that maintaining an optimal diet<span class="elsevierStyleSup">6</span> and good physical condition<span class="elsevierStyleSup">7</span> is accompanied by a lower rate of cardiovascular complications and mortality, even for patients who are being treated with long-term statin therapy (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The data demonstrate the importance of following recommended healthy habits for patients being treated with lipid-lowering agents. Recommended healthy habits include following a Mediterranean diet that, according to data from PREDIMED study,<span class="elsevierStyleSup">8</span> results in reduced rates of cardiovascular complications of a magnitude similar to that achieved with statins.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">References</span><p id="par0375" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0180"><span class="elsevierStyleLabel">1.</span><p id="par0380" class="elsevierStylePara elsevierViewall">Armitage J, on behalf of the HPS2-THRIVE Collaborative Group. HPS2-THRIVE: randomized placebo-controlled trial of ER niacin and laropiprant in 25,673 patients with pre-existing cardiovascular disease. American College of Cardiology, 2013 Scientific Sessions. 9–11 March. San Francisco, USA.</p></li><li class="elsevierStyleListItem" id="lsti0185"><span class="elsevierStyleLabel">2.</span><p id="par0385" class="elsevierStylePara elsevierViewall">Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al.; dal-OUTCOMES Investigators. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367:2089–99.</p></li><li class="elsevierStyleListItem" id="lsti0190"><span class="elsevierStyleLabel">3.</span><p id="par0390" class="elsevierStylePara elsevierViewall">Sesso HD, Christen WG, Bubes <span class="elsevierStyleSmallCaps">V</span>, Smith JP, MacFadyen J, Schvartz M, et al. Multivitamins in the prevention of cardiovascular disease in men: the Physicians’ Health Study <span class="elsevierStyleSmallCaps">II</span> randomized controlled trial. JAMA. 2012;308:1751–60.</p></li><li class="elsevierStyleListItem" id="lsti0195"><span class="elsevierStyleLabel">4.</span><p id="par0395" class="elsevierStylePara elsevierViewall">Kwak SM, Myung SK, Lee YJ, Seo HG. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: A meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med. 2012;172:686–94.</p></li><li class="elsevierStyleListItem" id="lsti0200"><span class="elsevierStyleLabel">5.</span><p id="par0400" class="elsevierStylePara elsevierViewall">Myung SK, Ju W, Cho B, Oh SW, Park SM, Koo BK, et al. Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: Systematic review and meta-analysis of randomised controlled trials. Br Med J. 2013;346:f10.</p></li><li class="elsevierStyleListItem" id="lsti0205"><span class="elsevierStyleLabel">6.</span><p id="par0405" class="elsevierStylePara elsevierViewall">Dehghan M, Mente A, Teo KK, Gao P, Sleight P, Dagenais G, et al. Relationship between healthy diet and risk of cardiovascular disease among patients on drug therapies for secondary prevention: a prospective cohort study of 31<span class="elsevierStyleHsp" style=""></span>546 high-risk individuals from 40 countries. Circulation. 2012;126:2705–12.</p></li><li class="elsevierStyleListItem" id="lsti0210"><span class="elsevierStyleLabel">7.</span><p id="par0410" class="elsevierStylePara elsevierViewall">Kokkinos PF, Faselis C, Myers J, Panagiotakos D, Doumas M. Interactive effects of fitness and statin treatment on mortality risk in veterans with dyslipidaemia: a cohort study. Lancet. 2013;381:394–99.</p></li><li class="elsevierStyleListItem" id="lsti0215"><span class="elsevierStyleLabel">8.</span><p id="par0415" class="elsevierStylePara elsevierViewall">Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279–90.</p></li></ul></p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Diabetes mellitus</span><p id="par0420" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">P. Conthe Gutiérrez</span></p><p id="par0425" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Department of Internal Medicine, University General Hospital Gregorio Marañón, Madrid, Spain</span></p><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Algorithm of the American Diabetes Association–European Association for the Study of Diabetes</span><p id="par0430" class="elsevierStylePara elsevierViewall">Perhaps the main news of 2012 was the lack of major developments that have changed what we already knew after the publication of various clinical studies performed in recent years (ADVANCE,<span class="elsevierStyleSup">1</span> VADT,<span class="elsevierStyleSup">2</span> ACCORD,<span class="elsevierStyleSup">3</span> etc.) and that have provided a more cautious approach in the hypoglycemic strategy.</p><p id="par0435" class="elsevierStylePara elsevierViewall">The objectives in diabetes, apart from its prevention in susceptible individuals (which should be considered crucial), is increasingly focused on identifying new compounds that are able to control blood glucose with minimal risks while providing value-added effects for patients with diabetes. The new treatments attempt to not only maintain glycemic control and improve insulin action but also reverse or stop the loss of β-cell function, help lose weight (or at least to not increase weight), prevent hypoglycemia and be able to show a favorable long-term impact on CV disease. Over the course of the previous year, a clear trend has emerged toward the individualization of therapy, as shown by the ADA EASD algorithm<span class="elsevierStyleSup">4</span> revealed last year (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). The document has been thoroughly debated, especially at the EASD congress held in Berlin where the stage was set for the debate for and against the algorithm. The director of the NICE diabetes agency set out a serious critique of the document's supporting evidence and its preparation procedure, while recognizing the simplicity and practical interest of the clinical message, which can be summarized in the following points:<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0220"><span class="elsevierStyleLabel">1.</span><p id="par0440" class="elsevierStylePara elsevierViewall">Treat type 2 diabetes pharmacologically from the start, along with general measures.</p></li><li class="elsevierStyleListItem" id="lsti0225"><span class="elsevierStyleLabel">2.</span><p id="par0445" class="elsevierStylePara elsevierViewall">Establish, in most cases, the introduction of metformin from the start (except for obvious intolerance) above any other pharmaceutical option.</p></li><li class="elsevierStyleListItem" id="lsti0230"><span class="elsevierStyleLabel">3.</span><p id="par0450" class="elsevierStylePara elsevierViewall">If the glycemic control objectives are not achieved in 3 months, include other drugs in a stepwise fashion.</p></li></ul></p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0455" class="elsevierStylePara elsevierViewall">There are no data from long-term comparative efficacy studies that recommend one combination over other. Therefore, individualization of therapy based on patient characteristics is gaining relevance, taking into account factors such as patient commitment, the risks associated with hypoglycemia, disease duration, life expectancy, comorbidities and vascular complications, as well as available economic resources. This type of therapy emphasizes patient involvement and individualization of objectives.</p><p id="par0460" class="elsevierStylePara elsevierViewall">If there are major metabolic abnormalities in the diagnosis, combination therapy should be considered from the start.<span class="elsevierStyleSup">5,6</span></p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Bariatric surgery</span><p id="par0465" class="elsevierStylePara elsevierViewall">Regarding bariatric or metabolic surgery and other variant techniques, there are a large number of publications in high-impact journals, which include the comparison conducted by Schauer et al. between interventionism versus intensive medical treatment.<span class="elsevierStyleSup">7</span></p><p id="par0470" class="elsevierStylePara elsevierViewall">Increasingly larger series are being presented with longer follow-up periods that allow for more accurate assessment of the alleged “disappearance” of the diagnosis of diabetes (frequently defined by A1c<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>6.1%). This retrogradation of type 2 diabetes varies among various studies from 38% to 79%, with the greatest success when the duration of the disease is shorter and when more weight is lost. In addition, there is discussion about new less aggressive approaches to classical techniques that can produce a similar effect, such as an “intestinal condom” (luminal sheath that hinders the absorption of food), implantable by endoscopy, with acceptable results at 1-year follow-up in a series with a small number of patients.</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Hyperglycemia in hospitalized patients</span><p id="par0475" class="elsevierStylePara elsevierViewall">One of the fruits of the consensus between several medical societies was the development of clinical practice guidelines for managing hyperglycemia in noncritical hospitalized patients in order to improve the metabolic situation of these patients in the hospital setting.<span class="elsevierStyleSup">8</span> Hospital hyperglycemia is defined as any glucose level above 140<span class="elsevierStyleHsp" style=""></span>mg/dl. In the hospital setting, hyperglycemia can appear not only in patients with diabetes but also in patients with no previous diagnosis of diabetes and in patients with stress hyperglycemia, which can occur during any acute process and is usually resolved by the time of hospital discharge. The treatment of choice for managing hospital hyperglycemia is insulin. Antidiabetic oral agents and injectable GLP-1 analogs should be avoided, except in highly selective cases. The most accepted regimen in noncritical patients is the basal-bolus regimen, in addition to a dose-adjustment regimen. In conclusion, as a general standard for controlling hyperglycemia in hospitalized patients, the following points should be considered:<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0235"><span class="elsevierStyleLabel">1.</span><p id="par0480" class="elsevierStylePara elsevierViewall">All patients previously treated with insulin should continue with subcutaneous insulin regimens during hospitalization.</p></li><li class="elsevierStyleListItem" id="lsti0240"><span class="elsevierStyleLabel">2.</span><p id="par0485" class="elsevierStylePara elsevierViewall">Rescue or sliding scale regimens should be avoided as the only therapy regimen with subcutaneous insulin.</p></li><li class="elsevierStyleListItem" id="lsti0245"><span class="elsevierStyleLabel">3.</span><p id="par0490" class="elsevierStylePara elsevierViewall">The subcutaneous insulin regimens should consist of baseline or intermediate insulin every 12 or 24<span class="elsevierStyleHsp" style=""></span>h, combined with fast or ultrafast insulin administered before meals.</p></li></ul></p><p id="par0495" class="elsevierStylePara elsevierViewall">It is therefore necessary to implement appropriate hyperglycemia treatment protocols in the various hospital centers that allow the various medical specialists, as well as nursing staff, to apply specific directives that facilitate the treatment of the various conditions related to hospital hyperglycemia. Diet is an essential element in the management of hospital hyperglycemia. Diets rich in carbohydrates provide a proper adjustment of prandial insulin dosage, avoid hypoglycemia and facilitate diabetes education during the hospital stay.</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">New treatments</span><p id="par0500" class="elsevierStylePara elsevierViewall">The analysis of data accumulated in pivotal trials on incretin drugs suggest that they might have a beneficial CV effect, although we still await the conclusion of studies designed to assess such effect.</p><p id="par0505" class="elsevierStylePara elsevierViewall">Gliflozins are a type of drug that inhibits the glucose and sodium transporter (SEC-2) in the proximal tubule, preventing the reabsorption of glucose and producing glycosuria. These drugs are currently in the marketing phase. In addition to improving glycemic control, they have a favorable effect on weight (−1.5 to −3<span class="elsevierStyleHsp" style=""></span>kg) and on blood pressure (−2 to −5<span class="elsevierStyleHsp" style=""></span>mmHg), which has been corroborated in various studies. Among its adverse effects, hypoglycemia is uncommon, but genital fungal infections in women and urinary tract infections require the identification of patients susceptible to the benefits of these drugs.</p><p id="par0510" class="elsevierStylePara elsevierViewall">Among the new insulins is the insulin degludec, which is a new generation insulin analog. Its ultralong effect is the result of the slow release of multihexamer monomers that form after the subcutaneous injection, which is thought to provide better glycemic control with a lower risk of hypoglycemia.</p></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">References</span><p id="par0515" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0250"><span class="elsevierStyleLabel">1.</span><p id="par0520" class="elsevierStylePara elsevierViewall">ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72.</p></li><li class="elsevierStyleListItem" id="lsti0255"><span class="elsevierStyleLabel">2.</span><p id="par0525" class="elsevierStylePara elsevierViewall">Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. for the VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129–39.</p></li><li class="elsevierStyleListItem" id="lsti0260"><span class="elsevierStyleLabel">3.</span><p id="par0530" class="elsevierStylePara elsevierViewall">The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59.</p></li><li class="elsevierStyleListItem" id="lsti0265"><span class="elsevierStyleLabel">4.</span><p id="par0535" class="elsevierStylePara elsevierViewall">Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364–79.</p></li><li class="elsevierStyleListItem" id="lsti0270"><span class="elsevierStyleLabel">5.</span><p id="par0540" class="elsevierStylePara elsevierViewall">Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. AACE comprehensive diabetes management algorithm 2013. Endocr Pract. 2013;19:327–36.</p></li><li class="elsevierStyleListItem" id="lsti0275"><span class="elsevierStyleLabel">6.</span><p id="par0545" class="elsevierStylePara elsevierViewall">Canadian Diabetes Association 2013. Available at: <a id="intr0020" class="elsevierStyleInterRef" href="http://guidelines.diabetes.ca/Browse.aspx">http://guidelines.diabetes.ca/Browse.aspx</a> [accessed 25.07.13].</p></li><li class="elsevierStyleListItem" id="lsti0280"><span class="elsevierStyleLabel">7.</span><p id="par0550" class="elsevierStylePara elsevierViewall">Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366:1567–76.</p></li><li class="elsevierStyleListItem" id="lsti0285"><span class="elsevierStyleLabel">8.</span><p id="par0555" class="elsevierStylePara elsevierViewall">Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:16–38.</p></li></ul></p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Vascular risk assessment</span><p id="par0560" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">J.<span class="elsevierStyleSmallCaps">I</span>. Cuende Melero</span></p><p id="par0565" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Department of Internal Medicine, Healthcare Complex of Palencia, Palencia, Spain</span></p><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Risk stratification</span><p id="par0570" class="elsevierStylePara elsevierViewall">The determination of cardiovascular (CV) risk in our patients is a requirement for establishing their therapeutic objectives and deciding on additional pharmacological interventions in addition to lifestyle changes. The quantification of CV risk is an area of continuous research.</p><p id="par0575" class="elsevierStylePara elsevierViewall">The 5th joint European prevention guidelines<span class="elsevierStyleSup">1</span> establishes 4 CV risk categories: low, moderate, high and very high. The very high risk category is new in the series of joint cardiovascular disease prevention guidelines and although it follows the line established in the 2011 European guidelines for managing dyslipidemia,<span class="elsevierStyleSup">2</span> they differ on an issue that can affect patients with renal damage. The dyslipidemia guidelines established a glomerular filtration rate lower than 60<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> as a qualifier of very high risk, while the new CV disease prevention guidelines adopt a more conservative positive, establishing a glomerular filtration rate lower than 60<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> as high risk and assigning the rate as very high risk only if it descends below 30<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>.</p><p id="par0580" class="elsevierStylePara elsevierViewall">Coupled with this new risk category, new therapeutic objectives have been established for controlling cholesterol levels. In low to moderate risk groups, an LDL-cholesterol level below 115<span class="elsevierStyleHsp" style=""></span>mg/dl is accepted as the objective, initiating a dietary and general health treatment and postponing drug therapy. In contrast, when the risk is high, the objective is an LDL-cholesterol level <100<span class="elsevierStyleHsp" style=""></span>mg/dl, starting drug therapy if the patient is not in a controlled situation. Furthermore, for the very high-risk class, the therapeutic objective is established at an LDL-cholesterol level <70<span class="elsevierStyleHsp" style=""></span>mg/dl, with drug therapy starting immediately if the patient is not in a controlled situation. Given that this last objective can be difficult to reach in certain starting situations, a reduction of at least 50% should be achieved, without forgetting that the primary objective is 70<span class="elsevierStyleHsp" style=""></span>mg/dl.</p><p id="par0585" class="elsevierStylePara elsevierViewall">Another important development of this European cardiovascular disease prevention guideline is the adoption of the vascular age calculation using SCORE in young subjects. As recorded in previous editions, it is known that young adults do not reach high risk even with significant simultaneous disorders of varying risk factor. This could deny them appropriate treatment. In addition to calculating the relative risk in these patients, the vascular age should be calculated. Although the guidelines do not provide the vascular age tables with SCORE (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>), they do list their reference published in 2010<span class="elsevierStyleSup">3</span> and dedicate a section of the guidelines to the concept of vascular age or age of risk.</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0590" class="elsevierStylePara elsevierViewall">The horizon of 10 years from which the absolute risk is calculated is the subject of controversy; other time intervals have therefore been sought, such as the risk at 30 years or the lifetime risk. Two interesting articles have been published that explore the lifetime risk,<span class="elsevierStyleSup">4,5</span> enabling the identification of subjects who, despite having a low short-term risk, can have a high lifetime risk. A methodological problem that has to be considered in the calculation of long-term risk is the correction that has to be applied due to the competitive risks of dying from non-CV causes.</p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Chronic inflammatory diseases and vascular risk</span><p id="par0595" class="elsevierStylePara elsevierViewall">Chronic inflammatory diseases increase CV risk. In recent years, the interest in quantifying this increase has grown, especially in chronic infectious diseases and chronic inflammatory connective tissue diseases. In the field of chronic infections, HIV infection represents an increased CV risk from both the underlying chronic inflammatory process and side effects of highly effective antiretroviral therapies. The chronicity resulting from the new antiretroviral treatments, especially since the introduction of antiprotease drugs, has demonstrated that the CV problems of patients infected by HIV have a special character and need their own systems for quantifying risk. D’Agostino<span class="elsevierStyleSup">6</span> reviewed these aspects and referenced the DAD study<span class="elsevierStyleSup">7</span> that showed the effect of indinavir, lopinavir and abacavir on this risk.</p><p id="par0600" class="elsevierStylePara elsevierViewall">Chronic connective tissue diseases are the other major group of diseases in which the important underlying inflammatory component modulates the CV risk significantly upwards. Systemic lupus erythematosus is the prototype of these chronic inflammatory diseases, demonstrating that the inflammatory activity level is related to the CV risk determined by coronary calcifications.<span class="elsevierStyleSup">8</span></p></span></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">References</span><p id="par0605" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0290"><span class="elsevierStyleLabel">1.</span><p id="par0610" class="elsevierStylePara elsevierViewall">Perk J, de Backer G, Gohlke H, Graham <span class="elsevierStyleSmallCaps">I</span>, Reiner Z, Verschuren M, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33:1635–701.</p></li><li class="elsevierStyleListItem" id="lsti0295"><span class="elsevierStyleLabel">2.</span><p id="par0615" class="elsevierStylePara elsevierViewall">European Association for Cardiovascular Prevention & Rehabilitation, Reiner Z, Catapano AL, de Backer G, Graham <span class="elsevierStyleSmallCaps">I</span>, Taskinen MR, Wiklund O, et al.; ESC Committee for Practice Guidelines (CPG) 2008–2010 and 2010–2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32:1769–818.</p></li><li class="elsevierStyleListItem" id="lsti0300"><span class="elsevierStyleLabel">3.</span><p id="par0620" class="elsevierStylePara elsevierViewall">Cuende JI, Cuende N, Calaveras-Lagartos J. How to calculate vascular age with the SCORE project scales: A new method of cardiovascular risk evaluation. Eur Heart J. 2010;31:2351–8.</p></li><li class="elsevierStyleListItem" id="lsti0305"><span class="elsevierStyleLabel">4.</span><p id="par0625" class="elsevierStylePara elsevierViewall">Wilkins JT, Ning H, Berry J, Zhao L, Dyer AR, Lloyd-Jones DM. Lifetime risk and years lived free of total cardiovascular disease. JAMA. 2012;308:1795–801.</p></li><li class="elsevierStyleListItem" id="lsti0310"><span class="elsevierStyleLabel">5.</span><p id="par0630" class="elsevierStylePara elsevierViewall">Berry JD, Dyer A, Cai <span class="elsevierStyleSmallCaps">X</span>, Garside DB, Ning H, Thomas A, et al. Lifetime risks of cardiovascular disease. N Engl J Med. 2012;366:321–9.</p></li><li class="elsevierStyleListItem" id="lsti0315"><span class="elsevierStyleLabel">6.</span><p id="par0635" class="elsevierStylePara elsevierViewall">D’Agostino RB Sr. Cardiovascular risk estimation in 2012: Lessons learned and applicability to the HIV population. J Infect Dis. 2012;205(Suppl. 3):S362–7.</p></li><li class="elsevierStyleListItem" id="lsti0320"><span class="elsevierStyleLabel">7.</span><p id="par0640" class="elsevierStylePara elsevierViewall">Friis-Møller N, Thiébaut R, Reiss P, Weber R, Monforte AD, de Wit S, et al.; DAD study group. Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study. Eur J Cardiovasc Prev Rehabil. 2010;17:491–501.</p></li><li class="elsevierStyleListItem" id="lsti0325"><span class="elsevierStyleLabel">8.</span><p id="par0645" class="elsevierStylePara elsevierViewall">Romero-Díaz J, Vargas-Vóracková F, Kimura-Hayama E, Cortázar-Benítez LF, Gijón-Mitre R, Criales S, et al. Systemic lupus erythematosus risk factors for coronary artery calcifications. Rheumatology (Oxford). 2012;51:110–9.</p></li></ul></p></span></span>"
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"nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sánchez Fuentes D, Suárez Fernández C, García-Bragado Dalmau F, Mostaza Prieto JM, Conthe Gutiérrez P, Cuende JI. ¿Qué ha habido de nuevo en riesgo vascular en el año 2012? Rev Clin Esp. 2013;213:442–452.</p>"
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"nota" => "<p class="elsevierStyleNotepara" id="npar0010">Summary of the round table conducted during the annual meeting of the vascular risk group of the Spanish Society of Internal Medicine (Lleida, April 2013), developed by the speakers, which summarized the most important developments for clinical practice published in the last year in the 5 most important areas of vascular risk: high blood pressure, antithrombotic therapy, dyslipidemia, diabetes mellitus and vascular risk assessment.</p>"
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"en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The LDL receptors capture the LDL-cholesterol in the blood (1). They are internalized through a process of endocytosis to form the endosome (2). After separating from of the LDL particle (3), the receptors are reused returning to the cell surface (4). The LDL receptors, which carry an attached PCSK9 molecule (5), are directed toward the lysosome for their destruction (6), after which they are not reused. The antibodies against protein PCSK9 enable a higher availability of receptors for LDL-cholesterol.</p>"
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<table border="0" frame="\n
\t\t\t\t\tvoid\n
\t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-head\n
\t\t\t\t " align="" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-head\n
\t\t\t\t " align="left" valign="\n
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\t\t\t\t" style="border-bottom: 2px solid black">PRESCAP 2002 (%) \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-head\n
\t\t\t\t " align="left" valign="\n
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\t\t\t\t" style="border-bottom: 2px solid black">PRESCAP 2006 (%) \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-head\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t" style="border-bottom: 2px solid black">PRESCAP 2010 (%) \t\t\t\t\t\t\n
\t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Control \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">36.1 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">41.4 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">46.3 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Monotherapy \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">56 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">44.4 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">36.4 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Two drugs \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
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\t\t\t\t">36.6 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">41.1 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">44.1 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Three drugs \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">8.4 \t\t\t\t\t\t\n
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\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
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\t\t\t\t">14.5 \t\t\t\t\t\t\n
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\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">19.51 \t\t\t\t\t\t\n
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