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Hernandez-Hernandez R, Andres Octavio-Seijas J, Lopez-Rivera J, et al., 2019, May measurement month 2017 campaign screening results from Venezuela: an analysis of blood pressure, abdominal circumference and body mass index, Investigacion clinica, Vol: 60, Pages: 319-335, ISSN: 0535-5133
The present study had the purpose of evaluating the proportion of subjects with hypertension, treatment, control rates, and the relationship between blood pressure (BP) with body mass index and abdominal circumference in a cross-sectional study, as part of a worldwide study designed by International Society of Hypertension, performed during May 2017. After the protocol´s approval by the local Ethical Committee, 64 sites were included from eight Venezuelan regions. A short questionnaire was completed for each participant, including knowledge of taking antihypertensive treatment, diabetes, previous myocardial infarction or stroke, alcohol intake, and smoking. BP was measured in the sitting position three times after resting for 5 minutes, one minute apart, using mainly oscillometric devices. Height, weight and abdominal circumference were measured. Data analyses were performed by the MMM central team. 21644 individuals were screened. After multiple imputations, 10584 individuals [48.9% (50.7% male; 47.7% female)] had hypertension. Of subjects not receiving antihypertensive medication, 1538 (12.2%) were hypertensives. Of hypertensive individuals receiving antihypertensive medication, 2974 (32.9%) had uncontrolled BP. 15.6% of our sample had obesity according to their body mass index; 43.8% of women and 20.7% of men had abdominal obesity. BP was positively correlated with BMI and abdominal circumference. In this largest BP screening carried out in Venezuela, 48.9% of the individuals had elevated BP and 12.2% did not know that they had hypertension, and in one third of those with hypertension on treatment, BP was not controlled. 15.6% had obesity by BMI, and 35.1% abdominal obesity. Screening such as the MMM17 can evaluate the association between hypertension and obesity and therefore may help to inform control programs.
Marinier K, Macouillard P, de Champvallins M, et al., 2019, Effectiveness of two-drug therapy versus monotherapy as initial regimen in hypertension: A propensity score-matched cohort study in the UK Clinical Practice Research Datalink, Pharmacoepidemiology and Drug Safety, Vol: 28, Pages: 1572-1582, ISSN: 1053-8569
PURPOSE: To compare the effectiveness on blood pressure (BP) of initial two-drug therapy versus monotherapy in hypertensive patients. METHODS: Using the Clinical Practice Research Datalink, linked with Hospital Episode Statistics and Office for National Statistics, we identified a cohort of adults with uncontrolled hypertension, initiating one or two antihypertensive drug classes between 2006 and 2014. New users of two drugs and monotherapy were matched 1:2 by propensity score. Main exposure was "as-treated," ie, until first regimen change. Primary and secondary endpoints were systolic and diastolic BP control and major adverse cardiovascular event (MACE), respectively. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard models. RESULTS: Of 54 523 eligible patients, 3256 (6.0%) were initiated to a two-drug combination. Of these, 2807 were matched to 5614 monotherapy users. Mean exposure duration was 12.7 months, with 76.5% patients changing their initial regimen. Two-drug therapy was associated with a clinically significant BP control increase in all hypertensive patients (HR = 1.17 [95%CI: 1.09-1.26]), more so in patients with grade 2-3 hypertension (HR = 1.28 [1.17-1.41]). An increase of 27% in BP control (HR = 1.27 [1.08-1.49]) was observed in patients initiating an ACEi+CCB combination compared with initiators of either single class. No significant association was found between two-drug therapy and MACE. Several sensitivity analyses confirmed the main findings. CONCLUSIONS: Few patients initiated therapy with two drugs, reflecting UK guidelines' recommendation to start with monotherapy. This study supports the greater effectiveness of two-drug therapy as the initial regimen for BP control.
Tremblay J, Haloui M, Harvey F, et al., 2019, Polygenic risk scores predict diabetic complications and their response to therapy
<jats:title>Abstract</jats:title><jats:p>Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction can lead to timely intervention and better outcomes. Through summary statistics of meta-analyses of published genome-wide association studies performed in over 1.2 million of individuals, we combined 9 PRS gathering genomic variants associated to cardiovascular and renal diseases and their key risk factors into one logistic regression model, to predict micro- and macrovascular endpoints of diabetes. Its clinical utility in predicting complications of diabetes was tested in 4098 participants with diabetes of the ADVANCE trial followed during a period of 10 years and replicated it in three independent non-trial cohorts. The prediction model adjusted for ethnicity, sex, age at onset and diabetes duration, identified the top 30% of ADVANCE participants at 3.1-fold increased risk of major micro- and macrovascular events (p=6.3×10<jats:sup>−21</jats:sup> and p=9.6×10<jats:sup>−31</jats:sup>, respectively) and at 4.4-fold (p=6.8×10<jats:sup>−33</jats:sup>) increased risk of cardiovascular death compared to the remainder of T2D subjects. While in ADVANCE overall, combined intensive therapy of blood pressure and glycaemia decreased cardiovascular mortality by 24%, the prediction model identified a high-risk group in whom this therapy decreased mortality by 47%, and a low risk group in whom the therapy had no discernable effect. Patients with high PRS had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. This novel polygenic prediction model identified people with diabetes at low and high risk of complications and improved targeting those at greater benefit from intensive therapy while avoiding unnecessary intensification in low-risk subjects.</jats:p>
Tack CJ, Jacob S, Desouza C, et al., 2019, Long-term efficacy and safety of combined insulin and glucagon-like peptide-1 therapy: Evidence from the LEADER trial, Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, Vol: 21, Pages: 2450-2458, ISSN: 1462-8902
AIM: Glucagon-like peptide-1 receptor agonist (GLP-1RA) and insulin combination therapy is an effective treatment option for type 2 diabetes, but long-term data are lacking. The aim was to assess the long-term efficacy of the GLP-1RA liraglutide in subgroups by insulin use in the LEADER trial. MATERIALS AND METHODS: LEADER assessed cardiovascular (CV) safety and efficacy of liraglutide (1.8 mg) versus placebo (plus standard of care therapy) in 9340 patients with type 2 diabetes and high risk of CV disease, for up to 5 years. We analyzed CV events, metabolic parameters and hypoglycaemia post hoc in three subgroups by baseline insulin use (basal-only insulin, other insulin or no insulin). Insulin was a non-random treatment allocation as part of standard of care therapy. RESULTS: At baseline, 5171 (55%) patients were not receiving insulin, 3159 (34%) were receiving basal-only insulin and 1010 (11%) other insulins. Insulin users had a longer diabetes duration and slightly worse glycaemic control (HbA1c) than the no-insulin subgroup. Liraglutide reduced HbA1c and weight versus placebo in all three subgroups (P < .001), and severe hypoglycaemia rate in the basal-only insulin subgroup. The need for insulin was less with liraglutide. CV risk reduction with liraglutide was similar to the main trial results in the basal-only and no-insulin subgroups. CONCLUSIONS: In patients on insulin, liraglutide improved glycaemic control, weight and need for insulin versus placebo, for at least 36 months with no increased risk of severe hypoglycaemia, while maintaining CV safety/efficacy, supporting the combination of liraglutide and insulin for management of type 2 diabetes.
Clark DW, Zhang W, Gao H, et al., 2019, Associations of autozygosity with a broad range of human phenotypes, Nature Communications, Vol: 10, ISSN: 2041-1723
In many species, the offspring of related parents suffer reduced vigor, survival and reproductive success, a phenomenon known as inbreeding depression1. In humans, the importance of this effect has remained unclear2, partly because reproduction between close relatives is both rare in many cultures and frequently associated with confounding social factors3. Here, using genomic inbreeding coefficients4 (FROH) for >1.3 million individuals, we show that FROH is significantly associated (P < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. Increased FROH is associated with reduced reproductive success (decreased number and likelihood of having children, older age at first sex and first birth, decreased number of sexual partners), as well as reduced risk-taking behaviour (alcohol intake, ever-smoked, self-reported risk taking) and increased disease risk (self-reported overall health, and risk factors including grip strength and heart rate). The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. These effects are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants causing inbreeding depression are predominantly rare. For a subset of traits, the effect of FROH differs significantly between men and women. Indeed, an increased FROH is associated with decreased total and LDL cholesterol in men, raising the possibility that increases in these traits may have benefited evolutionary fitness, despite being known coronary risk factors. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of environmental confounding. We conclude that inbreeding depression influences a broad range of human phenotypes through the action of rare, recessive variants.
Ojji DB, Poulter N, 2019, Comparison of dual therapies for lowering blood pressure in Black Africans. reply., New England Journal of Medicine, Vol: 381, Pages: 1392-1392, ISSN: 0028-4793
Erzurumluoglu AM, Chambers JC, Elliott P, et al., 2019, Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci, Molecular Psychiatry, Vol: 25, Pages: 2392-2409, ISSN: 1359-4184
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.
Berkelmans GFN, Gudbjornsdottir 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, European Heart Journal, Vol: 40, Pages: 2899-2906, ISSN: 0195-668X
AimsAlthough 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 resultsWe 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.ConclusionCardiovascular 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. Predictions
Carcel C, Neal B, Oparil S, et al., 2019, Clinical characteristics, antihypertensive medication use and blood pressure control among patients with treatment-resistant hypertension: the Survey of PatIents with treatment ResIstant hyperTension study., Journal of Hypertension, Vol: 37, Pages: 1-9, ISSN: 0263-6352
OBJECTIVE: We evaluated the characteristics of patients with treatment-resistant hypertension (TRH) and the prevalence of TRH in a large multicountry sample of specialist tertiary centres. METHODS: The Survey of PatIents with treatment ResIstant hyperTension (SPIRIT) study was a retrospective review of medical records of patients seen at tertiary centres located in Western Europe, Eastern Europe, North America, South America, Australia and Asia. Data on demographics, medical history and medication use were extracted from medical records. Prevalence and incidence of TRH were based upon estimated catchment populations. RESULTS: On thousand, five hundred and fifty-five patients from 76 centres were included, mostly from centres that specialize in hypertension (55%), cardiology (11%) or nephrology (19%). Mean age was 64, 60% were men, 62% were Caucasian, 36% had chronic kidney disease, 41% had diabetes, 12% were smokers and 31% had a previous cardiovascular event. Daytime and night-time ambulatory blood pressure (BP) was the most frequently used measurement for diagnosis (82%). Ninety-five percent of patients were prescribed diuretics, 93% an inhibitor of the renin-angiotensin system, 86% a calcium channel blocker, 74% a beta-blocker and 36% an aldosterone antagonist. The overall estimated mean incidence of TRH was 5.8 per 100 000 per year (ranging between 2.3 and 14.0 across regions) and the corresponding estimated mean prevalence of TRH was 23.9 per 100 000 (ranging between 7.6 and 90.5 across regions). CONCLUSION: Observed variation likely reflects real differences in patient characteristics and physician management practices across regions and specialities but may also reflect differences in patient selection and errors in estimation of catchment population across participating centres.
Mann I, Sasikaran T, Sandler B, et al., 2019, Ablation versus anti-arrhythmic therapy for reducing all hospital episodes from recurrent atrial fibrillation (AVATAR-AF): design and rationale, American Heart Journal, Vol: 214, Pages: 36-45, ISSN: 0002-8703
Atrial Fibrillation (AF) ablation using the cryoballoon is effective at reducing symptomatic AF episodes. The prevalence of AF is increasing with the aging population and access to such treatment would be enhanced by reducing the resource requirements. Relinquishing electrical mapping of the pulmonary veins (PV) removes the need for PV catheters, electrical recording equipment and staff trained in using this equipment. Moreover, the majority of complications are peri-procedural so overnight hospitalization maybe unnecessary. We tested this streamlined approach to AF ablation against medical therapy using the endpoint of time to all hospital episodes. METHODS: The AVATAR-AF study is a prospective, multicenter, randomized controlled trial testing the primary hypothesis that AF ablation done without PV mapping or overnight hospitalization is more effective than anti-arrhythmic drugs at reducing all hospital episodes related to recurrent atrial arrhythmias. We included a third arm to test a secondary hypothesis that confirming PV entrance block as per consensus guidelines can improve outcomes. Three hundred twenty-one patients with documented paroxysmal AF will be randomized in a 1:1:1 manner to one of three investigation arms: (1) AVATAR protocol cryoballoon ablation without assessment of acute PV isolation or overnight hospitalization; (2) medical therapy with anti-arrhythmic drugs; or (3) conventional cryoballoon ablation with assessment of acute PV isolation. The primary endpoint is defined as the time to all hospital episodes (including outpatient consultation) related to treatment for atrial arrhythmia. CONCLUSION: The AVATAR-AF study will determine whether the resource utilization for AF ablation can be reduced whilst maintaining superiority over medical therapy.
Sharma A, Jose AP, Pandey N, et al., 2019, A collaborative model for capacity building of primary care physicians in the management of Hypertension in India, JOURNAL OF HUMAN HYPERTENSION, Vol: 33, Pages: 562-565, ISSN: 0950-9240
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McDonnell B, Keitley J, Beaney T, et al., 2019, May measurement month 2017 and 2018: an analysis of blood pressure screening results from the UK and Republic of Ireland, 29th European Meeting of Hypertension and Cardiovascular Protection of the European-Society-of-Hypertension (ESH), Publisher: Lippincott, Williams & Wilkins, Pages: E44-E44, ISSN: 0263-6352
Objective: Elevated blood pressure (BP), or hypertension, is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and acting as a stimulus to improving screening programs worldwide. In the United Kingdom (UK) nearly 1 in 5 people, and in the Republic of Ireland (RoI) 3 out of 10, have hypertension, of which a large proportion remains undiagnosed.Design and method: An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017 and 2018. BP measurement, definition of hypertension and statistical analysis followed a standardized protocol. Screenings sites in hospitals, universities, shopping centres, workplaces, sports clubs, community centres, GP practices, and pharmacies were set up across the UK and RoI as part of this initiative.Results: 12,714 individuals were screened during MMM17&18. After multiple imputation, 4,815 (37.9%) had hypertension. Of individuals not receiving antihypertensive medication, 2,388 (23.3%) were hypertensive. Of individuals receiving antihypertensive medication, 1,038 (42.9%) had uncontrolled BP.Conclusions: MMM17&18 were the largest BP screening campaigns ever undertaken in the UK and RoI. These data prove for the first time that a relatively inexpensive, volunteer based, convenience sampling of screening blood pressure in the community identified 2 out of 5 individuals as hypertensive, with 1 in 4 not receiving treatment. Of major concern is that these data demonstrate that of those individuals receiving treatment, 2 out of 5 still did not have controlled BP.
Beaney T, Burrell LM, Castillo RR, et al., 2019, May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension, European Heart Journal, Vol: 40, Pages: 2006-2017, ISSN: 1522-9645
AIMS: Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. METHODS AND RESULTS: Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. CONCLUSION: May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk.
Poulter NR, Dolan E, Gupta AK, et al., 2019, Efficacy and safety of incremental dosing of a new single-pill formulation of perindopril and amlodipine in the management of hypertension, American Journal of Cardiovascular Drugs, Vol: 19, Pages: 313-323, ISSN: 1175-3277
BACKGROUND: Angiotensin-converting enzyme inhibitors and calcium channel blockers in combination are widely recommended in hypertension guidelines. The advantages of single-pill combinations (SPCs) are increasingly recognized, so a dosage-adapted combination of perindopril and amlodipine was developed for the initial management of hypertension. OBJECTIVE: This randomized trial evaluated the blood pressure (BP)-lowering efficacy of four incremental doses of perindopril/amlodipine SPC in adults with mild-to-severe hypertension. METHODS: Eligible patients (N = 1617) were randomized to SPC perindopril 3.5 mg/amlodipine 2.5 mg (i.e., 3.5/2.5 mg) daily, uptitrating as required on a monthly basis up to 14/10 mg until BP < 140/90 mmHg (< 130/80 mmHg in patients with diabetes). The primary endpoint (proportion with controlled BP at each uptitrated dose) was evaluated at 6 months, and safety was evaluated at 9 months; 24-h ambulatory BP measurement and BP variability were also investigated. Control-arm participants (n = 1653) were randomized to irbesartan 150 mg daily, uptitrating over 3 months to irbesartan/hydrochlorothiazide 300/25 mg. RESULTS: Significant increases in BP control were observed with each dosage increment of perindopril/amlodipine, which was well tolerated, rising from 21% (3.5/2.5 mg) to 30% (7/5 mg), 37% (14/5 mg), and 42% (14/10 mg) after 1, 2, 3, and 6 months, respectively. Reductions in mean systolic and diastolic BP occurred with each incremental dose of perindopril/amlodipine. After 6 months, mean BP had fallen by 24.8/10.8 mmHg. Irbesartan-based therapy reduced clinic and 24-h BP similarly to perindopril/amlodipine, but perindopril/amlodipine reduced BP variability more in comparison. CONCLUSIONS: Incremental uptitration with dosage-adapted perindopril/amlodipine SPC is a safe and effective strategy for mana
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, Vol: 85, Pages: 946-955, ISSN: 0006-3223
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.
de Vries PS, Brown MR, Bentley AR, et al., 2019, Multi-ancestry genome-wide association study of lipid levels incorporating gene-alcohol interactions, American Journal of Epidemiology, Vol: 188, Pages: 1033-1054, ISSN: 1476-6256
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.
Mann JFE, Fonseca V, Mosenzon O, et al., 2019, Response by Mann et al to Letter Regarding Article, "Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease: Results From the LEADER Trial", Circulation, Vol: 139, Pages: e1017-e1018, ISSN: 0009-7322
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, Obesity and Metabolism, Vol: 21, Pages: 1506-1512, ISSN: 1462-8902
In this post hoc analysis we investigated the effects of insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus comparators on cardiovascular (CV) risk markers in participants in the DUAL II (vs. insulin degludec), DUAL V (vs. insulin glargine 100 units/mL) and DUAL VII (vs. basal-bolus therapy) trials, 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 glycated haemoblogin (DUAL II, DUAL V), body weight (all three trials), systolic blood pressure (BP; all three trials), HDL cholesterol (DUAL VII) and LDL cholesterol (DUAL II, DUAL V). Higher heart rates were seen with IDegLira versus comparators (all three trials) plus significantly higher diastolic BP in men (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 cholesterol (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.
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, Obesity and Metabolism, Vol: 21, Pages: 1437-1444, ISSN: 1462-8902
AIM: To compare the associations between concomitant liraglutide use versus no liraglutide use and the risk of major adverse cardiovascular events (MACE) and all-cause mortality among patients receiving basal insulin (either insulin degludec [degludec] or insulin glargine 100 units/mL [glargine U100]) 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). MATERIALS AND METHODS: Patients with type 2 diabetes 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 were 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 type 2 diabetes and high cardiovascular risk using basal insulin.
Rahimi K, Canoy D, Nazarzadeh M, et al., 2019, Investigating the stratified efficacy and safety of pharmacological blood pressure-lowering: an overall protocol for individual patient-level data meta-analyses of over 300 000 randomised participants in the new phase of the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), BMJ Open, Vol: 9, Pages: 1-7, ISSN: 2044-6055
Introduction Previous research from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) and others has shown that pharmacological blood pressure (BP)- lowering substantially reduces the risk of major cardiovascular events, including ischaemic heart disease, heart failure and stroke. In this new phase, the aim is to conduct individual patient-level data (IPD) meta-analyses involving eligible BP-lowering randomised controlled trials (RCTs) to address uncertainties relating to efficacy and safety of BP-lowering treatment.Methods and analysis RCTs investigating the effect of pharmacological BP-lowering, with a minimum of 1000 patient-years of follow-up in each trial arm, are eligible. Our systematic review identified 100 potentially eligible trials. We requested their investigators/sponsors to contribute baseline, follow-up and outcomes data. As of June 2018, the collaboration has obtained data from 49 trials (n=315 046 participants), with additional data currently in the process of being transferred from four RCTs (n=34 642 participants). In addition, data harmonisation has commenced. Scientific activities of the collaboration are overseen by the Steering Committee with input from all collaborators. Detailed protocols for individual meta-analyses will be developed and registered on public platforms.Ethics and dissemination Ethics approval has been obtained for this new and extended phase of the BPLTTC, the largest collaboration of de-identified IPD from RCTs. It offers an efficient and ethical manner of re-purposing existing data to answer clinically important questions relating to BP treatment as well as methodological questions relating to IPD meta-analyses. Among the immediate impacts will include reliable quantification of effects of treatment modifiers, such as baseline BP, age and prior disease, on both vascular and non-vascular outcomes. Analyses will further assess the impact of BP-lowering on important, but less well und
Hernández-Hernández R, Octavio-Seijas JA, Morr I, et al., 2019, Results of the May measurement month 2017: blood pressure campaign in Venezuela-Americas., European Heart Journal Supplements, Vol: 21, Pages: D124-D126, ISSN: 1520-765X
Cardiovascular diseases, mainly coronary heart disease and stroke, are the first cause of death in Venezuela; and hypertension is the main risk factor. May Measurement Month (MMM) is a global initiative aimed at raising awareness of elevated blood pressure (BP) and to act as a temporary solution to the lack of regular screening programmes. Some representative studies indicate prevalence of hypertension in Venezuela between 24 and 39%, and control rate around 20%. Sixty-four sites were included to participate in MMM, mainly in pharmacies. Physical measurements included height, weight, and abdominal circumference. Blood pressure was measured in the sitting position three times after resting for 5 min, 1 min apart, using validated oscillometric devices. 21 644 individuals were screened. After multiple imputation, 10 584 individuals [48.9% (50.7% male; 47.7% female)] had hypertension. Of individuals not receiving antihypertensive medication, 1538 (12.2%) were hypertensive. Of individuals receiving antihypertensive medication, 2974 (32.9%) had uncontrolled BP. About 16% had obesity calculated by body mass index; 43.8% of women and 20.7% of men had abdominal obesity. This was the largest BP screening carried out in Venezuela, in which 48.9% of the individuals had elevated BP, untreated hypertension was 12.2%, and one-third of subjects taking treatment were not controlled. About 16% had obesity by body mass index, and abdominal obesity is more common in women. These results suggest that repeated screening like MMM17 can identify hypertension in important numbers and can also evaluate programmes of hypertension treatment and control in Venezuela.
Goma FM, Mwewa B, Tembo GK, et al., 2019, May measurement month 2017: Blood pressure screening results from Zambia-Sub-Saharan Africa., European Heart Journal Supplements, Vol: 21, Pages: D130-D132, ISSN: 1520-765X
Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. Prevalence of hypertension is reported to reach 34% in some areas of Zambia but public awareness is reportedly low. A majority of individuals do not know that they have high BP and others do not take any medication. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. Measurement sites were set-up at shopping malls, markets, sports facilities, churches, higher institutions of learning, and urban clinics. A total of 9607 individuals were screened during MMM17. After multiple imputation, 2438 (25.9%) had hypertension. Of individuals not receiving anti-hypertensive medication, 1706 (19.6%) were hypertensive. Of individuals receiving anti-hypertensive medication, 438 (62%) had uncontrolled BP. The MMM for 2017 was the largest BP screening campaign undertaken in Zambia. The campaign identified 2438 individuals with hypertension who were given heart health advice and/or referred to the local clinic for treatment. These results suggest that a large BP screening campaign based on convenience sampling could be a useful and reasonably inexpensive tool to help raise awareness in the general population and thereby help address the burden of disease caused by hypertension.
Ndhlovu HLL, Masiye JK, Chinula G, et al., 2019, May Measurement Month 2017: results of a blood pressure screening campaign in Malawi-Sub-Saharan Africa, European Heart Journal Supplements, Vol: 21, Pages: D74-D76, ISSN: 1520-765X
Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programs worldwide. A World Health Organization and Ministry of Health STEPS Survey conducted in 2009 in Malawi found that 32.9% tested positive for age-standardized hypertension. The survey further showed that three-quarters (75%) of the participants never had their BP measured before and 94.9% with high BP were unaware of the hypertensive condition. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. BP measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. The screening took place in cities of Lilongwe and Blantyre mostly in hospitals, clinics, marketplaces, workplaces, and churches. About 4009 individuals were screened during MMM17. After multiple imputations, 849 (22.3%) had hypertension. Of individuals not receiving antihypertensive medication, 697 (19.1%) were found to have hypertension. Only 152 individuals were receiving antihypertensive medication, and of these 78 (51.4%) had uncontrolled BP. MMM17 was the largest BP screening campaign ever undertaken in Malawi. The results identified a large number with hypertension who were not on treatment and over half of those on antihypertensive treatment who were uncontrolled, indicating the need for better management of cases. These results suggest that opportunistic screening can identify significant numbers with raised BP.
Poulter NR, Borghi C, Castillo RR, et al., 2019, May Measurement Month 2017: Results of 39 national blood pressure screening programmes, European Heart Journal Supplements, Vol: 21, Pages: D1-D4, ISSN: 1520-765X
Raised blood pressure is the biggest single risk factor responsible for mortality worldwide. Despite this, the majority of people with hypertension are unaware of having it, are untreated, or are on treatment but uncontrolled. May Measurement Month is a global campaign initiated by the International Society of Hypertension with the aim of raising awareness of high blood pressure. In the first year of the campaign in 2017, over 1.2 million people were screened in 80 countries across the world, finding over 100 000 people with hypertension who were not on treatment and over 150 000 people on anti-hypertensive treatment who were not controlled. The individual national results from 39 countries are presented in this supplement. In this article, we discuss the background to the campaign, along with some of the logistical and methodological challenges that were faced in setting up the campaign, and in collecting and analysing the data from such a large cross-sectional study. With the lessons learned from the 2017 campaign, the campaign was repeated in 2018 and is to be repeated again in 2019.
Victória Pereira S, Valentim M, Feijão A, et al., 2019, May Measurement Month 2017: an analysis of blood pressure screening in Angola-Sub-Saharan Africa, European Heart Journal Supplements, Vol: 21, Pages: D5-D7, ISSN: 1520-765X
Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. There is increasing prevalence of hypertension in developing countries leading to increased risk of adverse outcomes. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. In Angola, 17 481 individuals were screened in six provinces with an average BP of 126/78 mmHg. After multiple imputation, 6022 (34.5%) had hypertension. Of individuals not receiving antihypertensive medication, 4080 (26.3%) were hypertensive. Of those receiving antihypertensive medication, 1159 (59.7%) had uncontrolled BP. MMM17 was the largest BP screening campaign undertaken in Angola. These results suggest that there is still a significant percentage of patients who are not medicated and possibly require medication, and more than half of the hypertensive patients do not have controlled BP demonstrating the need for a more targeted and comprehensive screening of BP and more effective treatment.
Marin MJ, Garcia Vasquez F, Martinez Marissi E, et al., 2019, May Measurement Month 2017: analysis of the blood pressure screening results in Argentina-Americas, European Heart Journal Supplements, Vol: 21, Pages: D8-D10, ISSN: 1520-765X
Hypertension is a growing concern worldwide, causing over 10 million deaths each year. The prevalence of high blood pressure (BP) in Argentina is 36.3% and 38% of these are unaware of their disease. Half of the hypertensive patients are on pharmacological treatment and only a quarter of them are controlled. The International Society of Hypertension initiated the May Measurement Month (MMM) as a global campaign to raise awareness on high BP that may also serve as a temporary solution to the lack of global screening programs worldwide. A volunteer cross-sectional survey was carried out in May 2017 across 56 health centres. Blood pressure measurement, definition of hypertension and statistical analysis followed the MMM protocol. For this awareness campaign, the Argentine Society of Hypertension coined the slogan: 'Know and control your blood pressure'. A total of 32 346 individuals aged at least 18 years were screened during MMM17. After imputation, 16 263 (50.4%) were hypertensive. Of the 12 156 receiving antihypertensive medication 5400 (44.4%) still had uncontrolled BP. MMM17, called in our country 'Know and control your blood pressure', was the largest BP screening campaign done in Argentina. Almost 6 out of 10 hypertensive patients were either not on treatment or were not controlled to the BP goal. These results suggest that appropriate screening can help to identify a significant number of people with high BP.
Zelveian P, Avagyan A, Minasyan A, et al., 2019, May Measurement Month 2017: an analysis of blood pressure screening results in Armenia-Europe, European Heart Journal Supplements, Vol: 21, Pages: D11-D13, ISSN: 1520-765X
Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. The study was conducted in public areas (14 sites in Yerevan and 18 in regions), both indoor and outdoor, as well as in 42 primary care centres. A total of 9199 individuals were screened during MMM17 of which 9186 had three BP measurements available. The mean age of screened individuals was 50 ± 16.7 years, 57.3% was female. At the time of screening 17.9% were on antihypertensive medication. After imputation, a percentage of participants with hypertension was 33.9%, and 52.9% of them were on treatment. Of those treated, 77.0% had uncontrolled BP. MMM17 was the largest BP screening campaign undertaken in Armenia. We found that in Armenia, untreated hypertension is common, as is not adequately treated hypertension.
Carnagarin R, Fonseca R, Brockman D, et al., 2019, May Measurement Month 2017: an analysis of blood pressure screening results from Australia-South-East Asia and Australasia, European Heart Journal Supplements, Vol: 21, Pages: D14-D16, ISSN: 1520-765X
Increased blood pressure (BP) is the single biggest contributing risk factor to the global disease burden. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension aimed at raising awareness of high BP. In Australia, hypertension affects around six million adults and continues to remain the greatest attributable cause of cardiovascular mortality and morbidity (48.3%), stroke deaths (28%), and kidney disease (14%). An opportunistic cross-sectional survey was carried out during May 2017 predominantly in capital cities across Australia which included adult volunteers. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. Additional information obtained included anthropometric data and responses to questionnaires on demographic, lifestyle, and environmental factors. Data were collected from 3817 individuals. After multiple imputation, of the 3758 individuals for whom a mean of the second and third BP reading was available, 1188 (31.2%) had hypertension. Of 3213 individuals not receiving antihypertensive treatment, 591 (18.4%) were hypertensive, and 239 (40.1%) of the 596 individuals receiving treatment had uncontrolled BP. Adjusted BP was higher in association with antihypertensive medication, cerebrovascular disease, smoking, and alcohol consumption. Blood pressure was higher when measured on the right arm and on Tuesdays. MMM17 was one of the largest BP screening campaigns undertaken in Australia using standardized BP measurements. In line with previous surveys, around one-third of screened adults had hypertension and approximately 40% of treated individuals remained uncontrolled. These results suggest that opportunistic screening can identify significant numbers with raised BP.
Perl S, Zweiker D, Niederl E, et al., 2019, May Measurement Month 2017: an analysis of blood pressure screening results in Austria-Europe, European Heart Journal Supplements, Vol: 21, Pages: D17-D20, ISSN: 1520-765X
Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programs worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. Blood pressure measurement, the definition of hypertension (HTN), and statistical analysis followed the standard MMM protocol. In total, 2711 individuals (58.6% female) were screened during MMM17 in 56 centres. After multiple imputation, 1704 (62.9%) had HTN (≥140/90 mmHg). Of individuals not receiving antihypertensive medication, 764 (43.2%) were hypertensive. Of individuals receiving antihypertensive medication, 597 (63.5%) had uncontrolled BP. MMM17 was one of the largest BP screening campaigns undertaken in Austria. A large number of undiagnosed hypertensives was found and connected to a therapeutic strategy. An alarming number of uncontrolled but treated hypertensives should attract the attention of doctors and health care system in Austria.
Barbosa E, Eibel B, Brandão AA, et al., 2019, May Measurement Month 2017: Brazilian results-Americas, European Heart Journal Supplements, Vol: 21, Pages: D25-D27, ISSN: 1520-765X
Hypertension is a pathology of high prevalence in the world. In Brazil, it is the main risk factor for the major cause of death in the country, coronary heart disease. The May Measurement Month Campaign in 2017 (MMM17) included a population with representation from all Brazilian states and reflects some of the characteristics of hypertension in Brazil. Questionnaire data were collected and three measures of blood pressure (BP) were performed. The sample consisted of 7260 individuals, 40% were white, 56.4% were women. The average age was 52 years. Diabetes was present in 11.9%, previous myocardial infarction in 4.0% and stroke in 2.7%. About 8.4% were smokers and 26.2% were users of alcoholic drinks. The average BMI was 26.9 kg/m2. Considering the means of the last two measures of BP 47.0% were hypertensive (>140/90 mmHg). Of the individuals who did not use medication, 19.5% were hypertensive and of those who used anti-hypertensive medication 40.0% were uncontrolled. Systolic BP increased with age. The use of alcohol was related to higher BP levels, as well as diabetes and obesity. The MMM17 campaign demonstrated a large number of unknown hypertensives and a high rate of uncontrolled hypertension in Brazil.
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