553 results found
Brown-Frandsen K, Emerson SS, McGuire DK, et al., 2019, Lower rates of cardiovascular events and mortality associated with liraglutide use in patients treated with basal insulin - A DEVOTE subanalysis (DEVOTE 10)., Diabetes Obes Metab
AIMS: In patients with type 2 diabetes (T2D) and high cardiovascular risk, the cardiovascular safety of insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100) has been established, as has the superior efficacy of liraglutide versus placebo on major adverse cardiovascular events (MACE) and mortality. Here, the associations with risk of MACE and mortality are compared between liraglutide versus no liraglutide use in the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE; NCT01959529). MATERIALS AND METHODS: Patients with T2D and high cardiovascular risk were randomized 1:1 to degludec or glargine U100. Hazard ratios for MACE/mortality were calculated using a Cox regression model adjusted for treatment and time-varying liraglutide use at any time during the trial, without interaction. Sensitivity analyses adjusted for baseline covariates including, but not limited to, age, sex, smoking and prior cardiovascular disease. RESULTS: At baseline, 436/7637 (5.7%) patients were treated with liraglutide; after baseline, 187/7637 (2.4%) started and 210/7637 (2.7%) stopped liraglutide. Mean liraglutide exposure from randomization was 530.2 days. Liraglutide use versus no liraglutide use was associated with significantly lower hazard rates for MACE (0.62 [0.41; 0.92]95%CI ) and all-cause mortality (0.50 [0.29; 0.88]95%CI ). There was no significant difference in the rate of severe hypoglycaemia with versus without liraglutide use. Multiple sensitivity analyses yielded similar results. CONCLUSIONS: Use of liraglutide was associated with significantly lower risk of MACE and death in patients with T2D and high cardiovascular risk using basal insulin. This article is protected by copyright. All rights reserved.
Vilsbøll T, Blevins TC, Jodar E, et al., 2019, Fixed-ratio combination of insulin degludec and liraglutide (IDegLira) improves cardiovascular risk markers in patients with type 2 diabetes uncontrolled on basal insulin., Diabetes Obes Metab
This post hoc analysis investigated effects of insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus comparators on cardiovascular (CV) risk markers from DUAL II (versus insulin degludec), DUAL V (versus insulin glargine 100 units/mL) and DUAL VII (versus basal-bolus therapy) in patients grouped by sex, age (<65 years, ≥65 years) and diabetes duration (<10 years, ≥10 years). Treatment contrasts were in favour of IDegLira in many subgroups for changes from baseline in HbA1c (DUAL II, DUAL V), body weight (all three trials), systolic blood pressure (BP; all three trials), high-density lipoprotein cholesterol (DUAL VII) and low-density lipoprotein cholesterol (LDL-C; DUAL II, DUAL V). Higher heart rates were seen with IDegLira versus comparators (all three trials) plus significantly higher diastolic BP in males (DUAL V). Differences in treatment effect were seen between sexes in waist circumference (DUAL II), systolic BP (DUAL II, DUAL V) and triglycerides (DUAL VII), and between diabetes durations in LDL-C (DUAL V). In conclusion, IDegLira is associated with a general improvement in CV risk markers compared with basal insulin or basal-bolus therapy after 26 weeks of treatment. This article is protected by copyright. All rights reserved.
Fulcher J, Mihaylova B, O'Connell R, et al., 2019, Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials, LANCET, Vol: 393, Pages: 407-415, ISSN: 0140-6736
de Vries PS, Brown MR, Bentley AR, et al., 2019, Multi-Ancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions., Am J Epidemiol
An individual's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multi-ancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in Stage 1 (genome-wide discovery) and 66 studies in Stage 2 (focused follow-up), for a total of 394,584 individuals from five ancestry groups. Genetic main and interaction effects were jointly assessed by a 2 degrees of freedom (DF) test, and a 1 DF test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in Stage 1 and were evaluated in Stage 2, followed by combined analyses of Stage 1 and Stage 2. In the combined analysis of Stage 1 and Stage 2, 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2 DF tests, of which 18 were novel. No genome-wide significant associations were found testing the interaction effect alone. The novel loci included several genes (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.
Berkelmans GFN, Gudbjörnsdottir S, Visseren FLJ, et al., 2019, Prediction of individual life-years gained without cardiovascular events from lipid, blood pressure, glucose, and aspirin treatment based on data of more than 500 000 patients with Type 2 diabetes mellitus., Eur Heart J
Aims: Although group-level effectiveness of lipid, blood pressure, glucose, and aspirin treatment for prevention of cardiovascular disease (CVD) has been proven by trials, important differences in absolute effectiveness exist between individuals. We aim to develop and validate a prediction tool for individualizing lifelong CVD prevention in people with Type 2 diabetes mellitus (T2DM) predicting life-years gained without myocardial infarction or stroke. Methods and results: We developed and validated the Diabetes Lifetime-perspective prediction (DIAL) model, consisting of two complementary competing risk adjusted Cox proportional hazards functions using data from people with T2DM registered in the Swedish National Diabetes Registry (n = 389 366). Competing outcomes were (i) CVD events (vascular mortality, myocardial infarction, or stroke) and (ii) non-vascular mortality. Predictors were age, sex, smoking, systolic blood pressure, body mass index, haemoglobin A1c, estimated glomerular filtration rate, non- high-density lipoprotein cholesterol, albuminuria, T2DM duration, insulin treatment, and history of CVD. External validation was performed using data from the ADVANCE, ACCORD, ASCOT and ALLHAT-LLT-trials, the SMART and EPIC-NL cohorts, and the Scottish diabetes register (total n = 197 785). Predicted and observed CVD-free survival showed good agreement in all validation sets. C-statistics for prediction of CVD were 0.83 (95% confidence interval: 0.83-0.84) and 0.64-0.65 for internal and external validation, respectively. We provide an interactive calculator at www.U-Prevent.com that combines model predictions with relative treatment effects from trials to predict individual benefit from preventive treatment. Conclusion: Cardiovascular disease-free life expectancy and effects of lifelong prevention in terms of CVD-free life-years gained can be estimated for people with T2DM using readily available clinical characteristics. Predic
Erzurumluoglu AM, Liu M, Jackson VE, et al., 2019, Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci., Mol Psychiatry
Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
Ohkuma T, Jun M, Rodgers A, et al., 2019, Acute Increases in Serum Creatinine After Starting Angiotensin-Converting Enzyme Inhibitor-Based Therapy and Effects of its Continuation on Major Clinical Outcomes in Type 2 Diabetes Mellitus: The ADVANCE Trial, HYPERTENSION, Vol: 73, Pages: 84-91, ISSN: 0194-911X
Giri A, Hellwege JN, Keaton JM, et al., 2019, Trans-ethnic association study of blood pressure determinants in over 750,000 individuals, NATURE GENETICS, Vol: 51, Pages: 51-+, ISSN: 1061-4036
Brazel DM, Jiang Y, Hughey JM, et al., 2019, Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use, Biological Psychiatry, ISSN: 0006-3223
© 2018 Society of Biological Psychiatry Background: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. Methods: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. Results: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. Conclusions: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.
Verma S, Poulter NR, Bhatt DL, et al., 2018, Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke., Circulation, Vol: 138, Pages: 2884-2894
BACKGROUND: The glucagon-like peptide-1 analog liraglutide reduced cardiovascular events and mortality in patients with type 2 diabetes mellitus in the LEADER trial (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes). In a post hoc analysis, we evaluated the efficacy of liraglutide in those with and without a history of myocardial infarction (MI) and/or stroke. METHODS: LEADER was a randomized trial of liraglutide (1.8 mg or maximum tolerated dose) versus placebo in 9340 patients with type 2 diabetes mellitus and high cardiovascular risk, with a median follow-up of 3.8 years. The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (major adverse cardiovascular events). Risk groups in this post hoc analysis were defined by history of MI/stroke, established atherosclerotic cardiovascular disease without MI/stroke, or cardiovascular risk factors alone. RESULTS: Of the 9340 patients, 3692 (39.5%) had a history of MI/stroke, 3083 (33.0%) had established atherosclerotic cardiovascular disease without MI/stroke, and 2565 (27.5%) had risk factors alone. Major adverse cardiovascular events occurred in 18.8% of patients with a history of MI/stroke (incidence rate, 5.0 per 100 patient-years), 11.6% of patients with established atherosclerotic cardiovascular disease without MI/stroke (incidence rate, 3.0 per 100 patient-years), and 9.8% of patients with cardiovascular risk factors alone (incidence rate, 2.6 per 100 patient-years). Liraglutide reduced major adverse cardiovascular events in patients with a history of MI/stroke (322 of 1865 [17.3%] versus 372 of 1827 patients [20.4%]; hazard ratio, 0.85; 95% CI, 0.73-0.99) and in those with established atherosclerotic cardiovascular disease without MI/stroke (158 of 1538 [10.3%] versus 199 of 1545 patients [12.9%]; hazard ratio, 0.76; 95% CI, 0.62-0.94) compared with placebo. In patients with risk factors alone, the hazard ratio for liraglutide versus placebo was 1.08 (95% CI, 0.84-1.3
Mann JFE, Fonseca V, Mosenzon O, et al., 2018, Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease., Circulation, Vol: 138, Pages: 2908-2918
BACKGROUND: LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of CV Outcome Results) results demonstrated cardiovascular benefits for patients with type 2 diabetes mellitus at high cardiovascular risk on standard of care randomized to liraglutide versus placebo. The effect of glucagon-like peptide-1 receptor agonist liraglutide on cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus and chronic kidney disease is unknown. Liraglutide's treatment effects in patients with and without kidney disease were analyzed post hoc. METHODS: Patients were randomized (1:1) to liraglutide or placebo, both in addition to standard of care. These analyses assessed outcomes stratified by baseline estimated glomerular filtration rate (eGFR; <60 versus ≥60 mL/min/1.73 m2) and baseline albuminuria. The primary outcome (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and secondary outcomes, including all-cause mortality and individual components of the primary composite outcome, were analyzed using Cox regression. RESULTS: Overall, 2158 and 7182 patients had baseline eGFR <60 or ≥60 mL/min/1.73 m2, respectively. In patients with eGFR <60 mL/min/1.73 m2, risk reduction for the primary composite cardiovascular outcome with liraglutide was greater (hazard ratio [HR], 0.69; 95% CI, 0.57-0.85) versus those with eGFR ≥60 mL/min/1.73 m2 (HR, 0.94; 95% CI, 0.83-1.07; interaction P=0.01). There was no consistent effect modification with liraglutide across finer eGFR subgroups (interaction P=0.13) and when analyzing eGFR as a continuous variable (interaction P=0.61). Risk reductions in those with eGFR <60 versus ≥60 mL/min/1.73 m2 were as follows: for nonfatal myocardial infarction, HR, 0.74; 95% CI, 0.55-0.99 versus HR, 0.93; 95% CI, 0.77-1.13; for nonfatal stroke, HR, 0.51; 95% CI, 0.33-0.80 versus HR, 1.07; 95% CI, 0.84-1.37; for cardiovascular death, HR, 0.67; 95% CI, 0.50-0.90 ver
Evangelou E, Warren HR, Mosen-Ansorena D, et al., 2018, Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018), NATURE GENETICS, Vol: 50, Pages: 1755-1755, ISSN: 1061-4036
Bentley AR, Evangelou E, Zhang W, et al., Multi-ancestry genome-wide smoking interaction study of 387,272 individuals identifies novel lipid loci., Nature Genetics, ISSN: 1061-4036
Serum lipids, such as triglycerides (TG) and high- and low-density lipoprotein cholesterol (HDL and LDL), are influenced by both genetic and lifestyle factors. Over 250 lipid loci have been identified,1-6 yet, it is unclear to what extent lifestyle factors modify the effects of these variants, or those yet to be identified. Smoking is associated with an unfavorable lipid profile,7,8 warranting its investigation as a lifestyle factor that potentially modifies genetic associations with lipids. Identifying interactions using traditional 1 degree of freedom (1df) tests of SNP x smoking terms may have low power, except in very large sample sizes. To enhance the detection of loci, a 2 degree of freedom (2df) test that jointly evaluates the interaction and main effects was developed.9 The Gene-Lifestyle Interactions Working Group, under the aegis of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium10, was formed to conduct analyses of lifestyle interactions in the genetic basis of cardiovascular traits. As both genetic and lifestyle factors differ across populations with different ancestry backgrounds, and to address the underrepresentation of non-European populations in genomic research, great effort went into creating a large, multi-ancestry resource for these investigations.11 Here, we report a genome-wide interaction study that uses both the 1df test of interaction and the 2df joint test of main and interaction effects to test the hypothesis that genetic associations of serum lipids differ by smoking status.
Mentz RJ, Bethel MA, Merrill P, et al., 2018, Effect of Once-Weekly Exenatide on Clinical Outcomes According to Baseline Risk in Patients With Type 2 Diabetes Mellitus: Insights From the EXSCEL Trial., J Am Heart Assoc, Vol: 7
Background In the EXSCEL (Exenatide Study of Cardiovascular Event Lowering), exenatide once-weekly resulted in a nonsignificant reduction in major adverse cardiovascular events ( MACEs ) and a nominal 14% reduction in all-cause mortality in 14 752 patients with type 2 diabetes mellitus (T2 DM ) with and without cardiovascular disease. Whether patients at increased risk for events experienced a comparatively greater treatment benefit with exenatide is unknown. Methods and Results In the EXSCEL population, we created risk scores for MACEs and all-cause mortality using step-wise selection of baseline characteristics. A risk score was calculated for each patient, and a time-to-event model for each end point was developed including the risk score, treatment assignment, and risk-treatment interaction. Interaction P values evaluating for a differential treatment effect by baseline risk were reported. Over a median follow-up of 3.2 years (interquartile range, 2.2, 4.4), 1091 (7.4%) patients died and 1744 (11.8%) experienced a MACE . Independent predictors of MACEs and all-cause mortality included age, sex, comorbidities (eg, previous cardiovascular event), body mass index, blood pressure, hemoglobin A1c, and estimated glomerular filtration rate. The all-cause mortality and MACE risk models had modest discrimination with optimism-corrected c-indices of 0.73 and 0.71, respectively. No interaction was observed between treatment effect and risk profile for either end point (both interactions, P>0.1). Conclusions Baseline characteristics (eg, age, previous cardiovascular events) and routine laboratory values (eg, hemoglobin A1c, estimated glomerular filtration rate) provided modest prognostic value for mortality and MACEs in a broad population of patients with type 2 diabetes mellitus. Exenatide's effects on mortality and MACEs were consistent across the spectrum of baseline risk. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: N
Evangelou E, Warren HR, Mosen-Ansorena D, et al., 2018, Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits, NATURE GENETICS, Vol: 50, Pages: 1412-+, ISSN: 1061-4036
Carcel C, Neal B, Oparil S, et al., 2018, PREVALENCE AND CLINICAL CHARACTERISTICS OF PATIENTS WITH TREATMENT RESISTANT HYPERTENSION BY REGION: THE SPIRIT STUDY, 27th Scientific Meeting of the International-Society-of-Hypertension, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E306-E306, ISSN: 0263-6352
Gupta A, Mackay J, Whitehouse A, et al., 2018, BASELINE PREDICTORS OF ALL-CAUSE- AND CARDIOVASCULAR- MORTALITY AMONGST 8580 HYPERTENSIVE PATIENTS FOLLOWED UP FOR 16 YEARS IN THE ASCOT LEGACY STUDY, 27th Scientific Meeting of the International-Society-of-Hypertension, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E251-E251, ISSN: 0263-6352
Poulter NR, Savopoulos C, Anjum A, et al., 2018, Randomized Crossover Trial of the Impact of Morning or Evening Dosing of Antihypertensive Agents on 24-Hour Ambulatory Blood Pressure: The HARMONY Trial, HYPERTENSION, Vol: 72, Pages: 870-873, ISSN: 0194-911X
Gupta A, Mackay J, Whitehouse A, et al., 2018, Long-term mortality after blood pressure-lowering and lipid-lowering treatment in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy study: 16-year follow-up results of a randomised factorial trial, LANCET, Vol: 392, Pages: 1127-1137, ISSN: 0140-6736
Dzudie A, Ojji D, Damasceno A, et al., 2018, Development of the certificate course in the management of hypertension in Africa (CCMH-Africa): proceedings of the first continental faculty meeting, Nairobi, Kenya, 25-26 February 2018., Cardiovasc J Afr, Vol: 29, Pages: 331-334
BACKGROUND: In response to the call by the World Health Organisation to reduce premature deaths from non-communicable diseases by 25% by the year 2025 (25×25), the Pan-African Society of Cardiology (PASCAR), in partnership with several organisations, including the World Heart Federation, have developed an urgent 10-point action plan to improve detection, treatment and control of hypertension in Africa. Priority six of this action plan is to promote a task-shifting/task-sharing approach in the management of hypertension. AIM: This capacity-building initiative aims to enhance the knowledge, skills and core competences of primary healthcare physicians in the management of hypertension and related complications. METHODS: In a collaborative approach with the International Society of Hypertension, the British and Irish Hypertension Society, the Public Health Foundation of India and the Centre for Chronic Disease Control, the PASCAR hypertension taskforce held a continental faculty meeting in Kenya on 25 and 26 February 2018 to review and discuss a process of effective contextualisation and implementation of the Indian hypertension management course on the African continent. RESULTS: A tailored African course in terms of evidence-based learning, up-to-date curriculum and on-the-job training was developed with a robust monitoring and evaluation strategy. The course will be offered on a modular basis with a judicious mix of case studies, group discussions and contact sessions, with great flexibility to accommodate participants' queries. CONCLUSIONS: Hypertension affects millions of people in Africa and if left untreated is a major cause of heart disease, kidney disease and stroke. CCMH-Africa will train in the next 10 years, 25 000 certified general physicians and 50 000 nurses, capable of adequately managing uncomplicated hypertension, thereby freeing the few available specialists to focus on severe or complicated cases.
Laurent S, Mancia G, Poulter N, 2018, Perindopril 3.5 mg/amlodipine 2.5 mg versus renin-angiotensin system inhibitor monotherapy as first-line treatment in hypertension: a combined analysis., J Hypertens, Vol: 36, Pages: 1915-1920
BACKGROUND: Many patients are diagnosed with hypertension each year, making rapid and effective control of blood pressure (BP) crucial. Appropriate first-line treatment is important, and special attention should be paid to the positive effects of lowering BP early. Perindopril 3.5 mg/amlodipine 2.5 mg (P3.5/A2.5) is a single-pill combination suitable for first-line use. The doses of each component of the single-pill combination were selected for a first-line setting. OBJECTIVE: To investigate the effectiveness of the P3.5/A2.5 combination at lowering BP compared with renin-angiotensin system (RAS)-inhibitor monotherapies, after 1 month of treatment. METHODS: Individual patient data from three randomized controlled trials were used to evaluate the efficacy of P3.5/A2.5 versus RAS-inhibitor monotherapies after 1 month in 5496 patients with hypertension, in a combined analysis. RESULTS: P3.5/A2.5 was well tolerated and significantly more effective at reducing BP after 1 month than RAS-inhibitor monotherapies (perindopril 5 mg, irbesartan 150 mg or valsartan 80 mg). P3.5/A2.5 was associated with a significantly lower SBP (P = 0.002) and DBP (P = 0.005) after 1 month of treatment compared with RAS-inhibitor monotherapies. CONCLUSION: In a large patient population, early administration of P3.5/A2.5 resulted in a significantly greater BP-lowering effect than perindopril, irbesartan or valsartan monotherapies after 1 month. Reducing BP levels within a month of treatment may reasonably be expected to lead to a reduced risk of cardiovascular events.
Ojji DB, Poulter N, Damasceno A, et al., 2018, Rationale and design of the comparison of 3 combination therapies in lowering blood pressure in black Africans (CREOLE study): 2 × 3 factorial randomized single-blind multicenter trial., Am Heart J, Vol: 202, Pages: 5-12
BACKGROUND: Current hypertension guidelines recommend the use of combination therapy as first-line treatment or early in the management of hypertensive patients. Although there are many possible combinations of blood pressure(BP)-lowering therapies, the best combination for the black population is still a subject of debate because no large randomized controlled trials have been conducted in this group to compare the efficacy of different combination therapies to address this issue. METHODS: The comparison of 3 combination therapies in lowering BP in the black Africans (CREOLE) study is a randomized single-blind trial that will compare the efficacy of amlodipine plus hydrochlorothiazide versus amlodipine plus perindopril and versus perindopril plus hydrochlorothiazide in blacks residing in sub-Saharan Africa (SSA). Seven hundred two patients aged 30-79 years with a sitting systolic BP of 140 mm Hg and above, and less than 160 mm Hg on antihypertensive monotherapy, or sitting systolic BP of 150 mm Hg and above, and less than 180 mm Hg on no treatment, will be centrally randomized into any of the 3 arms (234 into each arm). The CREOLE study is taking place in 10 sites in SSA, and the primary outcome measure is change in ambulatory systolic BP from baseline to 6 months. The first patient was randomized in June 2017, and the trial will be concluded by 2019. CONCLUSIONS: The CREOLE trial will provide unique information as to the most efficacious 2-drug combination in blacks residing in SSA and thereby inform the development of clinical guidelines for the treatment of hypertension in this subregion.
Poulter NR, Castillo R, Charchar FJ, et al., 2018, Are the American Heart Association/American College of Cardiology High Blood Pressure Guidelines Fit for Global Purpose?: Thoughts From the International Society of Hypertension., Hypertension, Vol: 72, Pages: 260-262
Rådholm K, Chalmers J, Ohkuma T, et al., 2018, Use of the waist-to-height ratio to predict cardiovascular risk in patients with diabetes: Results from the ADVANCE-ON study., Diabetes Obes Metab, Vol: 20, Pages: 1903-1910
AIMS: Patients with type 2 diabetes have a high risk of cardiovascular disease (CVD). Central obesity has been particularly associated with this risk relationship. We aimed to evaluate waist to height ratio (WHtR) as a predictor of risk in such patients. METHODS: WHtR was evaluated as a predictor of the risk of CVD and mortality amongst 11 125 participants with type 2 diabetes in the ADVANCE and ADVANCE-ON studies, and was compared with body mass index (BMI), waist circumference and waist hip ratio (WHR). Primary outcome was a composite of death from CVD, non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes were myocardial infarction, stroke, cardiovascular death and death from any cause. Cox models were used, with bootstrapping to compare associations between anthropometric measures for the primary outcome. RESULTS: Median follow-up time was 9.0 years. There was a positive association between WHtR and adverse outcomes. The hazard ratio (HR) (confidence interval), per SD higher WHtR, was 1.16 (1.11-1.22) for the primary endpoint, with no heterogeneity by sex or region, but a stronger effect in individuals aged 66 years or older. The other 3 anthropometric measurements showed similar associations, although there was evidence that WHtR marginally outperformed BMI and WHR. Based on commonly used BMI cut-points, the equivalent WHtR cut-points were estimated to be 0.55 and 0.6, with no evidence of a difference across subgroups. CONCLUSIONS: In patients with diabetes, WHtR is a useful indicator of future adverse risk, with similar effects in different population subgroups.
Beaney T, Schutte AE, Tomaszewski M, et al., 2018, May Measurement Month 2017: an analysis of blood pressure screening results worldwide, LANCET GLOBAL HEALTH, Vol: 6, Pages: E736-E743, ISSN: 2214-109X
Stergiou GS, Dolan E, Kollias A, et al., 2018, Blood pressure measurement in special populations and circumstances., J Clin Hypertens (Greenwich), Vol: 20, Pages: 1122-1127
According to the established validation protocols, a typical validation study of a blood pressure (BP) monitor includes general population adults with normal or elevated BP. It is recognized, however, that the automated (oscillometric) BP monitors may have different accuracy or uses in some special populations compared with adults in the general population. Thus, an automated BP monitor with proven accuracy in a general population of adults may not be accurate in a special population, and therefore separate validation is needed. Recognized special populations deserving separate validation are those for which there is theoretical, and also clinical evidence, that the accuracy of BP monitors in these groups differs from that in the general population. Young children, pregnant women (including those with preeclampsia), individuals with arm circumference >42 cm, and patients with atrial fibrillation are regarded as special populations. Adolescents, individuals older than 80 years, and patients with end-stage renal disease or diabetes mellitus have also been considered as possible special groups, but there is still inadequate evidence of altered accuracy of BP monitors in these subjects. Validation studies should be performed in special populations and evaluated separately after the BP-measuring device has successfully undergone a validation study in a general population (unless the test device is intended only for a special population). This article discusses issues relating to the measurement of BP and the diagnosis of hypertension in selected special populations, as well as in low-resource settings, where a simplified yet efficient evaluation strategy is necessary.
Welsh P, Rankin N, Li Q, et al., 2018, Circulating amino acids and the risk of macrovascular, microvascular and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE trial., Diabetologia, Vol: 61, Pages: 1581-1591
AIMS/HYPOTHESES: We aimed to quantify the association of individual circulating amino acids with macrovascular disease, microvascular disease and all-cause mortality in individuals with type 2 diabetes. METHODS: We performed a case-cohort study (N = 3587), including 655 macrovascular events, 342 microvascular events (new or worsening nephropathy or retinopathy) and 632 all-cause mortality events during follow-up, in a secondary analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study. For this study, phenylalanine, isoleucine, glutamine, leucine, alanine, tyrosine, histidine and valine were measured in stored plasma samples by proton NMR metabolomics. Hazard ratios were modelled per SD increase in each amino acid. RESULTS: In models investigating associations and potential mechanisms, after adjusting for age, sex and randomised treatment, phenylalanine was positively, and histidine inversely, associated with macrovascular disease risk. These associations were attenuated to the null on further adjustment for extended classical risk factors (including eGFR and urinary albumin/creatinine ratio). After adjustment for extended classical risk factors, higher tyrosine and alanine levels were associated with decreased risk of microvascular disease (HR 0.78; 95% CI 0.67, 0.91 and HR 0.86; 95% CI 0.76, 0.98, respectively). Higher leucine (HR 0.79; 95% CI 0.69, 0.90), histidine (HR 0.89; 95% CI 0.81, 0.99) and valine (HR 0.79; 95% CI 0.70, 0.88) levels were associated with lower risk of mortality. Investigating the predictive ability of amino acids, addition of all amino acids to a risk score modestly improved classification of participants for macrovascular (continuous net reclassification index [NRI] +35.5%, p < 0.001) and microvascular events (continuous NRI +14.4%, p = 0.012). CONCLUSIONS/INTERPRETATION: We report distinct associations between circulat
Thomas MC, Woodward M, Li Q, et al., 2018, Relationship Between Plasma 8-OH-Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial., J Am Heart Assoc, Vol: 7
BACKGROUND: 8-Oxo-2'-deoxyguanosine (8-oxo-2'-dG) is a biomarker of oxidative DNA damage that is associated with cardiovascular disease and premature mortality in the general population. Although oxidative stress has a proven role in cardiovascular complications in diabetes mellitus, evidence for a relationship between plasma 8-oxo-2'-dG and major cardiovascular outcomes in diabetes mellitus is weak. METHODS AND RESULTS: A case-cohort study was performed in 3766 participants with prevalent diabetes mellitus in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) trial (ClinicalTrials.gov number NCT00145925). The hazard ratios for mortality and major acute cardiovascular events were derived using Cox regression models. During a median of 5 years of follow-up, 695 (18.4%) participants in this enriched cohort died (including 354 deaths from cardiovascular disease). Individuals with higher levels of 8-oxo-2'-dG were more likely to die. After adjusting for cardiovascular disease risk factors, the hazard ratio for a 1-SD increase in plasma 8-oxo-2'-dG was 1.10 (95% confidence interval, 1.01-1.20; P=0.03). This was driven by an independent association between plasma 8-oxo-2'-dG and cardiovascular death (hazard ratio, 1.23; 95% confidence interval, 1.10-1.37 [P<0.001]). By contrast, no association was seen between 8-oxo-2'-dG and noncardiovascular disease death (of which cancer was the major single cause). 8-Oxo-2'-dG was also not significantly associated with either nonfatal myocardial infarction or nonfatal stroke. CONCLUSIONS: In adults with type 2 diabetes mellitus, increased levels of 8-oxo-2'-dG are independently associated with all-cause mortality and cardiovascular mortality in adults with longstanding type 2 diabetes mellitus who participated in the ADVANCE trial, consistent with the role of oxidative damage in the development and progression of cardiovascular decompensation in diabetes mellitu
Feitosa MF, Kraja AT, Chasman DI, et al., 2018, Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries, PLOS ONE, Vol: 13, ISSN: 1932-6203
Gupta A, Mackay J, Whitehouse A, et al., 2018, DETERMINANTS OF LONG-TERM ALL-CAUSE AND CARDIOVASCULAR MORTALITY IN HYPERTENSIVE PATIENTS - FINDINGS FROM 16-YEAR FOLLOW-UP OF THE ASCOT LEGACY STUDY, 28th European Meeting of Hypertension and Cardiovascular Protection of the European-Society-of-Hypertension (ESH), Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E27-E27, ISSN: 0263-6352
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