Exploring the Interplay between Diabetes and Lp(a): Implications for Cardiovascular Risk.

PURPOSE OF REVIEW: The objective of this manuscript is to review and describe the relationship between Lp(a) and diabetes, exploring both their association and synergy as cardiovascular risk factors, while also describing the current evidence regarding the potential connection between low levels of Lp(a) and the presence of diabetes. RECENT FINDINGS: Epidemiological studies suggest a potential relationship between low to very low levels of Lp(a) and diabetes. Lipoprotein(a), or Lp(a), is an intriguing lipoprotein of genetic origin, yet its biological function remains unknown. Elevated levels of Lp(a) are associated with an increased risk of cardiovascular atherosclerosis, and coexisting diabetes status confers an even higher risk. On the other hand, epidemiological and genetic studies have paradoxically suggested a potential relationship between low to very low levels of Lp(a) and diabetes. While new pharmacological strategies are being developed to reduce Lp(a) levels, the dual aspects of this lipoprotein's behavior need to be elucidated in the near future.

Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension.

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.

Morning blood pressure surge as a predictor of cardiovascular events in patients with hypertension.

BACKGROUND: The prognostic value of ambulatory blood pressure (BP) monitoring (ABPM) is poorly understood in Latin American populations. METHODS: A prospective observational study was conducted on 1339 patients with hypertension who underwent 24-h BP monitoring between 2015 and 2019. The incidence of serious adverse cardiovascular events (MACE) was analysed using a Cox proportional hazards model adjusted for potential confounders. Three previously reported morning surge definitions were evaluated for SBP and DBP using different ABPM components: sleep-through morning surge, pre-awakening, and morning night-time difference. RESULTS: The mean age was 62 years, 52% were female, 32.8% had dyslipidaemia, 27.2% were smokers, and 7.8% had diabetes. During a median follow-up period of 32 months, 197 MACE occurred. In men, the adjusted hazard ratio (HR) was 1.84 [95% confidence interval (CI), 1.35-2.49; P < 0.001). The HR increased to 2.03 (95% CI, 1.89-2.17; P < 0.001) with a cut-off value of 35 mmHg for a 10 mmHg increase in sleep-through morning surge. The increased adjusted HR associated with the morning rise persisted for each secondary endpoint, including 21 cardiovascular deaths [HR: 2.70 (95% CI, 2.03-3.60; P < 0.001)], 78 myocardial infarctions [HR: 1.92 (95% CI, 1.72-2.15; P < 0.001)], 24 hospitalisations for heart failure [HR: 1.77 (95% CI, 1.48-2.12; P < 0.001)], 22 strokes [HR: 2.32 (95% CI, 1.85-2.91; P < 0.001)], and 52 atrial fibrillations [HR: 1.94 (95% CI, 1.71-2.20; P < 0.001)]. CONCLUSION: The morning BP rise was the most important circadian prognostic factor for MACE in patients with hypertension, which deserves more attention.

Position statement on use of pharmacological combinations in a single pill for treatment of hypertension by Argentine Federation of Cardiology (FAC) and Argentine Society of Hypertension (SAHA).

The present document provides scientific evidence reviewed and analysed by a group of specialist clinicians in hypertension that aims to give an insight into a pharmacological strategy to improve blood pressure control. Evidence shows that most hypertensive patients will need at least two drugs to achieve blood pressure goals. There is ample evidence showing that treatment adherence is inversely related to the number of drugs taken. Observational studies show that use of drug combinations to initiate treatment reduces the time to reach the treatment goal and reduces CVD, especially with single pill combinations (SPCs). This work, based on recommendations of the Argentine Federation of Cardiology and Argentine Society of Hypertension as a reference, aims to review the more recent evidence on SPC, and to serve as guidelines for health professionals in their clinical practice and to the wider use of SPCs for the treatment of hypertension. Evidence from clinical trials on the effectiveness and adverse effects of using SPCs are provided. An analysis is also made of the main contributions of SPCs in special populations, e.g., elderly and diabetic patients, and its use in high risk and resistant hypertension. The effects of SPCs on hypertensive-mediated organ damage is also examined. Finally, we provide some aspects to consider when choosing treatments in the economic context of Latin-America for promoting the most efficient use of resources in a scarce environment and to provide quality information to decision makers to formulate safe, cost-effective, and patient-centered health policies. Finally, future perspectives and limitations in clinical practice are also discussed.

The Attitudes of Physicians Toward Guideline Recommendations for the Management of Dyslipidemia in Clinical Practice - The VIPFARMA ISCP Project.

The aim of this study was to explore the different attitudes of physicians regarding international recommendations for the management of dyslipidemia in routine medical practice. Seven clusters of questions were designed to characterize the surveyed population. Eight hundred ninety-eight physicians answered the survey, 68.3% cardiologists and 40.0% had specialties related to cardiovascular prevention. 29.6% of physicians supported LDL goals above 70 mg/dL in secondary prevention. Acceptance of values lower than 70 mg/dL was associated with greater levels of continuing education (OR 0.64, 95% CI 0.45-0.91; P = 0.014), specialization in preventive cardiology (OR 0.49, 95% CI 0.28-0.88; P = 0.017) or diabetology (OR 0.48, 95% CI 0.24-0.98; P = 0.043). A less aggressive attitude toward the achievement of guideline goals were observed in physicians who considered LDL values higher than 70 mg/dL as the goal in secondary prevention. One-third of physicians in the survey do not follow goals recommended by international guidelines.

Impact of COVID-19 pandemic on cardiometabolic patients without SARS-CoV-2 infection in Latin America.

BACKGROUND AND OBJECTIVES: A cross-sectional survey including 38 questions about demography, clinical condition, changes in health habits, and medical treatments for cardiometabolic patients in outpatient follow-up was conducted. From June 15 to July 15, 2020, a total of 13 Latin-American countries participated in enrolling patients. METHODS: These countries were divided into 3 geographic regions: Region 1 including North, Central, and Caribbean Regions (NCCR), Region 2 including the Andean Region (AR), and Region 3 including the Southern Cone Region (SCR). 4.216 patients were analyzed, resulting in a coefficient of 33.82%, 32.23%, and 33.94% for NCCR, AR, and SCR, respectively. RESULTS: Significant differences were found between the AR, SCR, and NCCR regions. The analysis of habitual medication usage showed that discontinued use of medication was more present in AR, reaching almost 30% (p < 0.001). The main finding of this study was the negative impact that restrictive measures have on adherence to medications and physical activity: Rs = 0.84 (p = 0.0003) and Rs = 0.61 (p = 0.0032), respectively. AR was the most vulnerable region. CONCLUSION: Restrictive quarantine measures imposed by the different countries showed a positive correlation with medication discontinuation and a negative correlation with physical activity levels in patients analyzed. These findings characterize the impact of the consequences left by this pandemic. Undoubtedly, restrictive measures have been and will continue to have reverberating negative effects in most Latin-American countries.

ANTECEDENTES Y OBJETIVOS: Se realizó una encuesta transversal que incluyó 38 preguntas sobre demografía, estado clínico, cambio de hábitos de salud, tratamientos médicos a pacientes cardiometabólicos en seguimiento ambulatorio. Un total de 13 países latinoamericanos inscribieron pacientes del 15 de junio al 15 de julio de 2020. MÉTODO: Los países se dividieron en 3 regiones geográficas Región 1 (NCCR): Región Norte, Centro y Caribe; Región 2 (AR): Región Andina; Región 3 (SCR): Región Cono Sur. Las medidas de aislamiento se estimaron a partir de informes nacionales y se correlacionaron utilizando el coeficiente R de Spearman. Se analizaron 4.216 pacientes, NCCR (33.82%); AR (32.23%) SCR (33.94%). RESULTADOS: Se encontraron diferencias significativas entre regiones. Este análisis de la medicación habitual mostró que la discontinuación de la medicación fue mayor en RA, llegando a casi el 30% (p < 0.001). El principal hallazgo de este estudio fue el impacto negativo que tienen las medidas restrictivas sobre la adherencia a la medicación y la actividad física, Rs = 0.84 (p = 0.0003) y Rs = 0.61 (p = 0.0032), respectivamente. Se encontraron diferencias significativas entre regiones. AR es la región más vulnerable. CONCLUSIONES: Las medidas restrictivas impuestas por los diferentes países (cuarentena) mostraron una correlación positiva con la interrupción de la medicación y una correlación negativa con la cantidad de actividad física. El impacto de las consecuencias que deja esta pandemia será muy profundo en la mayoría de los países latinoamericanos.

Virtual management of hypertension: lessons from the COVID-19 pandemic-International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension.

The coronavirus disease 2019 pandemic caused an unprecedented shift from in person care to delivering healthcare remotely. To limit infectious spread, patients and providers rapidly adopted distant evaluation with online or telephone-based diagnosis and management of hypertension. It is likely that virtual care of chronic diseases including hypertension will continue in some form into the future. The purpose of the International Society of Hypertension's (ISH) position paper is to provide practical guidance on the virtual management of hypertension to improve its diagnosis and blood pressure control based on the currently available evidence and international experts' opinion for nonpregnant adults. Virtual care represents the provision of healthcare services at a distance with communication conducted between healthcare providers, healthcare users and their circle of care. This statement provides consensus guidance on: selecting blood pressure monitoring devices, accurate home blood pressure assessments, delivering patient education virtually, health behavior modification, medication adjustment and long-term virtual monitoring. We further provide recommendations on modalities for the virtual assessment and management of hypertension across the spectrum of resource availability and patient ability.

The worldwide impact of telemedicine during COVID-19: current evidence and recommendations for the future.

During the COVID-19 pandemic, telemedicine has emerged worldwide as an indispensable resource to improve the surveillance of patients, curb the spread of disease, facilitate timely identification and management of ill people, but, most importantly, guarantee the continuity of care of frail patients with multiple chronic diseases. Although during COVID-19 telemedicine has thrived, and its adoption has moved forward in many countries, important gaps still remain. Major issues to be addressed to enable large scale implementation of telemedicine include: (1) establishing adequate policies to legislate telemedicine, license healthcare operators, protect patients' privacy, and implement reimbursement plans; (2) creating and disseminating practical guidelines for the routine clinical use of telemedicine in different contexts; (3) increasing in the level of integration of telemedicine with traditional healthcare services; (4) improving healthcare professionals' and patients' awareness of and willingness to use telemedicine; and (5) overcoming inequalities among countries and population subgroups due to technological, infrastructural, and economic barriers. If all these requirements are met in the near future, remote management of patients will become an indispensable resource for the healthcare systems worldwide and will ultimately improve the management of patients and the quality of care.

Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.

BACKGROUND: Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19. METHODS: The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009. FINDINGS: Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m2 (SD 8), and 79 (52%) had diabetes. Compared with discontinuation of renin-angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40-110] for continuation vs 81 [38-117] for discontinuation; ß-coefficient 8 [95% CI -13 to 29]). There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ2 test of adverse events between treatment groups p=0·77). There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups. INTERPRETATION: Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19. FUNDING: REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.

The Global Ambulatory Blood Pressure Monitoring (ABPM) in Heart Failure with Preserved Ejection Fraction (HFpEF) Registry. Rationale, design and objectives.

Hypertension is a major risk factor for the development of heart failure with preserved ejection fraction (HFPEF) and blood pressure (BP) in itself is an important marker of prognosis. The association of BP levels, and hemodynamic parameters, measured by ambulatory blood pressure monitoring (ABPM), with outcomes, in patients with HFPEF is largely unknown. Patients with HFPEF have a substantial burden of co-morbidities and frailty. In addition there are marked geographic differences in HFPEF around the world. How these difference influence the association between BP and outcomes in HFPEF are unknown. The Global Ambulatory Blood Pressure Monitoring (ABPM) in Heart Failure with Preserved Ejection Fraction (HFpEF) Registry aims to assess the relevance of BP parameters, measured by ABPM, on the outcome of HFPEF patients worldwide. Additionally, the influence of other relevant factors such as frailty and co-morbidities will be assessed. Stable HFPEF patients with a previous hospitalization, will be included. Patients should be clinically and hemodynamically stable for at least 4 weeks before study inclusion. Specific data related to HF, biochemical markers, ECG and echocardiography will be collected. An ABPM and geriatric and frailty evaluation will be performed and the association with morbidity and mortality assessed. Follow up will be at least one year.

Randomized elimination and prolongation of ACE inhibitors and ARBs in coronavirus 2019 (REPLACE COVID) Trial Protocol.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), is associated with high incidence of multiorgan dysfunction and death. Angiotensin-converting enzyme 2 (ACE2), which facilitates SARS-CoV-2 host cell entry, may be impacted by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), two commonly used antihypertensive classes. In a multicenter, international randomized controlled trial that began enrollment on March 31, 2020, participants are randomized to continuation vs withdrawal of their long-term outpatient ACEI or ARB upon hospitalization with COVID-19. The primary outcome is a hierarchical global rank score incorporating time to death, duration of mechanical ventilation, duration of renal replacement or vasopressor therapy, and multiorgan dysfunction severity. Approval for the study has been obtained from the Institutional Review Board of each participating institution, and all participants will provide informed consent. A data safety monitoring board has been assembled to provide independent oversight of the project.

Impact of the Pandemic on NonInfected Cardiometabolic Patients: A Survey in Countries of Latin America-Rationale and Design of the CorCOVID LATAM Study.

BACKGROUND: The first case of coronavirus 2019 (COVID-19) in Latin America was detected on February 26th, 2020, in Brazil. Later, in June, the World Health Organization announced that the focus of the outbreak had shifted to Latin America, where countries already had poor control of indicators of noncommunicable diseases (NCDs). Concerns about coronavirus infection led to a reduced number of visits and hospitalizations in patients with NCDs, such as cardiovascular disease, diabetes, and cancer. There is a need to determine the impact of the COVID-19 pandemic on patients who have cardiometabolic diseases but do not have clinical evidence of COVID-19 infection. METHODS: The CorCOVID LATAM is a cross-sectional survey of ambulatory cardiometabolic patients with no history or evidence of COVID-19 infection. The study will be conducted by the Interamerican Society of Cardiology. An online survey composed of 38 questions using Google Forms will be distributed to patients of 13 Latin American Spanish-speaking countries from June 15th to July 15th, 2020. Data will be analyzed by country and regions. Seven clusters of questions will be analyzed: demographics, socioeconomic and educational level, cardiometabolic profile, lifestyle and habits, body-weight perception, medical follow-up and treatments, and psychological symptoms. RESULTS: Final results will be available upon completion of the study. CONCLUSIONS: The present study will provide answers regarding the impact of the COVID-19 pandemic on noninfected cardiometabolic patients. Data on this topic are scarce, as it is an unprecedented threat, without short-term solutions.

CONTEXTE: Le premier cas de maladie à coronavirus 2019 (COVID-19) en Amérique latine a été détecté le 26 février 2020 au Brésil. En juin, l'Organisation mondiale de la Santé a annoncé que le foyer de l'épidémie s'était déplacé en Amérique latine, où le suivi des indicateurs relatifs aux maladies non transmissibles est déjà déficient. Les préoccupations relatives à l'infection par le coronavirus ont entraîné une diminution du nombre de consultations et d'hospitalisations des patients atteints d'une maladie non transmissible, comme une ma-ladie cardiovasculaire, le diabète ou un cancer. Il est donc nécessaire d'évaluer l'incidence de la pandémie de COVID-19 chez les patients atteints d'une maladie cardiométabolique ne présentant aucun signe clinique d'une infection au virus de la COVID-19. MÉTHODOLOGIE: L'étude CorCOVID LATAM est une enquête transversale menée auprès des patients ambulatoires atteints d'une maladie cardiométabolique n'ayant pas d'antécédents d'infection au virus de la COVID-19 et ne présentant aucun signe d'une telle infection. L'étude est réalisée par la Société interaméricaine de cardiologie. Du 15 juin au 15 juillet 2020, on a demandé aux patients de 13 pays hispanophones d'Amérique latine de répondre à un questionnaire en ligne de 38 questions dans Google Forms. Les données seront analysées par pays et par région. Les réponses aux questions seront examinées selon sept grands thèmes : caractéristiques démographiques, caractéristiques socioéconomiques et niveau de scolarité, profil cardiométabolique, mode de vie et habitudes, perception quant au poids corporel, suivi et traitements médicaux et symptômes psychologiques. RÉSULTATS: Les résultats seront publiés à la fin de l'étude. CONCLUSIONS: L'étude fournira des renseignements sur l'incidence de la pandémie de COVID-19 chez les patients atteints d'une maladie cardiométabolique non infectés. Les données sur cette question sont rares, puisqu'il s'agit d'une menace sans précédent, à laquelle il n'existe de surcroît pas de solution à court terme.

Adherence to antihypertensive drug treatment in Argentina: A multicenter study.

Adherence to antihypertensive medication is an important challenge that doctors often face in the treatment of hypertension. Good adherence is crucial to prevent cardiovascular complications. In consequence, the present study aimed at determining the prevalence of adherence to antihypertensive treatment and identifying associated clinical variables. A multicenter cross-sectional study was conducted in 12 cities of Argentina. A systematic sampling was performed in order to select patients with hypertension and under pharmacological treatment for at least 6 months. Physicians took three BP measurements, and the level of adherence was assessed using the self-administered Morisky questionnaire (MMAS-8). Participants were classified into three levels of adherence: high adherence-MMAS score of 8; medium adherence-MMAS scores of 6 to <8; and low adherence-MMAS scores of <6. A total of 1111 individuals (62 ± 12 years old, women 49.4%) were included in the present analysis; 159 (14.3%), 329 (29.6%) and 623 (56.1%) patients had low, medium, and high adherence, respectively. The prevalence of controlled hypertension increased only in high adherent patients: 42.8%, 42.2%, and 64.5% for low, medium, and high adherence groups, respectively. Similarly, systolic BP was lower only in the high adherence group. High educational level (OR 3.47, 95% CI 2.68-4.49) and diuretic treatment (OR 0.64, 95% CI 0.47-0.88) were independent predictors of high adherence. In conclusion, more than a half of treated hypertensive patients had a high level of adherence. These patients had lower BP values and higher control levels. A high educational level predicts high adherence.

Blood pressure control and cardiovascular risk profile in hypertensive patients under specialist care in Argentina: Results from the CHARTER study.

Worldwide, hypertension control rate is far from ideal. Some studies suggest that patients treated by specialists have a greater chance to achieve control. The authors aimed to determine the BP control rate among treated hypertensive patients under specialist care in Argentina, to characterize patients regarding their cardiovascular risk profile and antihypertensive drug use, and to assess the variables independently associated with adequate BP control. The authors included adult hypertensive patients under stable treatment, managed in 10 specialist centers across Argentina. Office BP was measured thrice with a validated oscillometric device. Adequate BP control was defined as an average of the three readings <140/90 mm Hg (and <150/90 in patients older than 80 years). The authors estimated the proportion of adequate BP control and the variables independently associated with it through a multiple conditional logistic regression model. Among the 1146 included patients, 48.2% were men with a mean age of 63.5 (±13.1) years old. Mean office BP was 135.3 (±14.8)/80.8 (±10) mm Hg, with a 64.8% (95% CI: 62%-67.6%) of adequate control. The mean number of antihypertensive drugs was 2.1 per participant, the commonest being angiotensin receptor blockers and calcium channel blockers. In multivariable analysis, only female sex was a predictor of adequate BP control (OR 1.33 [95% CI 1.02-1.72], P = .04). In conclusion, almost 65% of hypertensive patients treated in specialist centers in Argentina have adequate BP control. The challenge for future research is to define strategies in order to translate this control rate to the primary care level, where most patients are managed.

MASked-unconTrolled hypERtension management based on office BP or on ambulatory blood pressure measurement (MASTER) Study: a randomised controlled trial protocol.

INTRODUCTION: Masked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM. METHODS AND ANALYSIS: MASTER is a 4-year prospective, randomised, open-label, blinded-endpoint investigation. A total of 1240 treated hypertensive patients from about 40 secondary care clinical centres worldwide will be included -upon confirming presence of MUCH (repeated on treatment OBP <140/90 mm Hg, and at least one of the following: daytime ABP ≥135/85 mm Hg; night-time ABP ≥120/70 mm Hg; 24 hour ABP ≥130/80 mm Hg), and will be randomised to a management strategy based on OBPM (group 1) or on ABPM (group 2). Patients in group 1 will have OBP measured at 0, 3, 6, 12, 18, 24, 30, 36, 42 and 48 months and taken as a guide for treatment; ABPM will be performed at randomisation and at 12, 24, 36 and 48 months but will not be used to take treatment decisions. Patients randomised to group 2 will have ABPM performed at randomisation and all scheduled visits as a guide to antihypertensive treatment. The effects of MUCH management strategy based on ABPM or on OBPM on CV and renal intermediate outcomes (changing left ventricular mass and microalbuminuria, coprimary outcomes) at 1 year and on CV events at 4 years and on changes in BP-related variables will be assessed. ETHICS AND DISSEMINATION: MASTER study protocol has received approval by the ethical review board of Istituto Auxologico Italiano. The procedures set out in this protocol are in accordance with principles of Declaration of Helsinki and Good Clinical Practice guidelines. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT02804074; Pre-results.

Effects of dipeptidyl-peptidase 4 inhibitor about vascular inflammation in a metabolic syndrome model.

BACKGROUND: In this study, we used vidagliptin(V) to examine the role of the DDP-IV, incretin system component, in the activation of different molecular inflammatory cytokines, NF-kB and VCAM-1 to generate a microenvironment that supports cardiovascular remodeling. METHODS: Male WKY and SHR were separated into five groups: Control, FFR: WKY rats receiving a 10% (w/v) fructose solution during all 12 weeks, SHR, FFHR: SHR receiving a 10% (w/v) fructose solution during all 12 weeks and FFHR+V: (5 mg/kg per day for 6 weeks) (n = 8 each group). Metabolic variables and systolic blood pressure were measured. The TBRAS, eNOS activity, and NAD(P)H oxidase activity were estimated to evaluate oxidative stress. Cardiac and vascular remodeling were evaluated. To assess the cytokine, NF-kB and VCAM-1 immunostaining techniques were used. RESULTS: The FFHR experimental model presents metabolic syndrome criteria, vascular and cardiac remodeling, vascular inflammation due to increased expression of NF-kB, VCAM-1, and pro-atherogenic cytokines. Chronic treatment with V was able to reverse total or partiality of variables studied. CONCLUSIONS: Data demonstrated an important effect of DDP-IV in reducing vascular inflammation, accompanied by a favorable reduction in metabolic and structural parameters.

Pathophysiology of vascular remodeling in hypertension.

Vascular remodeling refers to alterations in the structure of resistance vessels contributing to elevated systemic vascular resistance in hypertension. We start with some historical aspects, underscoring the importance of Glagov's contribution. We then move to some basic concepts on the biomechanics of blood vessels and explain the definitions proposed by Mulvany for specific forms of remodeling, especially inward eutrophic and inward hypertrophic. The available evidence for the existence of remodeled resistance vessels in hypertension comes next, with relatively more weight given to human, in comparison with animal data. Mechanisms are discussed. The impact of antihypertensive drug treatment on remodeling is described, again with emphasis on human data. Some details are given on the three mechanisms to date which point to remodeling resistance arteries as an independent predictor of cardiovascular risk in hypertensive patients. We terminate by considering the potential role of remodeling in the pathogenesis of endorgan damage and in the perpetuation of hypertension.

Melatonin, given at the time of reperfusion, prevents ventricular arrhythmias in isolated hearts from fructose-fed rats and spontaneously hypertensive rats.

Melatonin reduces reperfusion arrhythmias when administered before coronary occlusion, but in the clinical context of acute coronary syndromes, most of the therapies are administered at the time of reperfusion. Patients frequently have physiological modifications that can reduce the response to therapeutic interventions. This work determined whether acute melatonin administration starting at the moment of reperfusion protects against ventricular arrhythmias in Langendorff-perfused hearts isolated from fructose-fed rats (FFR), a dietary model of metabolic syndrome, and from spontaneous hypertensive rats (SHR). In both experimental models, we confirmed metabolic alterations, a reduction in myocardial total antioxidant capacity and an increase in arterial pressure and NADPH oxidase activity, and in FFR, we also found a decrease in eNOS activity. Melatonin (50 µm) initiated at reperfusion after 15-min regional ischemia reduced the incidence of ventricular fibrillation from 83% to 33% for the WKY strain, from 92% to 25% in FFR, and from 100% to 33% in SHR (P = 0.0361, P = 0.0028, P = 0.0013, respectively, by Fisher's exact test, n = 12 each). Although, ventricular tachycardia incidence was high at the beginning of reperfusion, the severity of the arrhythmias progressively declined in melatonin-treated hearts. Melatonin induced a shortening of the action potential duration at the beginning of reperfusion and in the SHR group also a faster recovery of action potential amplitude. We conclude that melatonin protects against ventricular fibrillation when administered at reperfusion, and these effects are maintained in hearts from rats exposed to major cardiovascular risk factors. These results further support the ongoing translation to clinical trials of this agent.