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1.
Nat Med ; 25(11): 1753-1760, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31700174

RESUMO

Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C-statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment.

2.
Mayo Clin Proc ; 94(11): 2230-2240, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31685151

RESUMO

OBJECTIVE: To investigate the associations of objectively measured cardiorespiratory fitness (CRF) and grip strength (GS) with incident heart failure (HF), a clinical syndrome that results in substantial social and economic burden, using UK Biobank data. PATIENTS AND METHODS: Of the 502,628 participants recruited into the UK Biobank between April 1, 2007, and December 31, 2010, a total of 374,493 were included in our GS analysis and 57,053 were included in CRF analysis. Associations between CRF and GS and incident HF were investigated using Cox proportional hazard models, with adjustment for known measured confounders. RESULTS: During a mean of 4.1 (range, 2.4-7.1) years, 631 HF events occurred in those with GS data, and 66 HF events occurred in those with CRF data. Higher CRF was associated with 18% lower risk for HF (hazard ratio [HR], 0.82; 95% CI, 0.76-0.88) per 1-metabolic equivalent increment increase and GS was associated with 19% lower incidence of HF risk (HR, 0.81; 95% CI, 0.77-0.86) per 5-kg increment increase. When CRF and GS were standardized, the HR for CRF was 0.50 per 1-SD increment (95% CI, 0.38-0.65), and for GS was 0.65 per 1-SD increment (95% CI, 0.58-0.72). CONCLUSION: Our data indicate that objective measurements of physical function (GS and CRF) are strongly and independently associated with lower HF incidence. Future studies targeting improving CRF and muscle strength should include HF as an outcome to assess whether these results are causal.

3.
BMJ Open ; 9(11): e030119, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31685500

RESUMO

OBJECTIVE: To determine the effects of yoga practice on subclinical cardiovascular measures, risk factors and neuro-endocrine pathways in patients undergoing cardiac rehabilitation (CR) following acute coronary events. DESIGN: 3-month, two-arm (yoga +usual care vs usual care alone) parallel randomised mechanistic study. SETTING: One general hospital and two primary care CR centres in London. Assessments were conducted at Imperial College London. PARTICIPANTS: 80 participants, aged 35-80 years (68% men, 60% South Asian) referred to CR programmes 2012-2014. INTERVENTION: A certified yoga teacher conducted yoga classes which included exercises in stretching, breathing, healing imagery and deep relaxation. It was pre-specified that at least 18 yoga classes were attended for inclusion in analysis. Participants and partners in both groups were invited to attend weekly a 6- to 12-week local standard UK National Health Service CR programme. MAIN OUTCOME MEASURES: (i) Estimated left ventricular filling pressure (E/e'), (ii) distance walked, fatigue and breathlessness in a 6 min walk test, (iii) blood pressure, heart rate and estimated peak VO2 following a 3 min step-test. Effects on the hypothalamus-pituitary-adrenal axis, autonomic function, body fat, blood lipids and glucose, stress and general health were also explored. RESULTS: 25 participants in the yoga + usual care group and 35 participants in the usual care group completed the study. Following the 3-month intervention period, E/e' was not improved by yoga (E/e': between-group difference: yoga minus usual care:-0.40 (-1.38, 0.58). Exercise testing and secondary outcomes also showed no benefits of yoga. CONCLUSIONS: In this small UK-based randomised mechanistic study, with 60 completing participants (of whom 25 were in the yoga + usual care group), we found no discernible improvement associated with the addition of a structured 3-month yoga intervention to usual CR care in key cardiovascular and neuroendocrine measures shown to be responsive to yoga in previous mechanistic studies. TRIAL REGISTRATION NUMBER: NCT01597960; Pre-results.

4.
Circ Cardiovasc Imaging ; 12(11): e009172, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31707792

RESUMO

BACKGROUND: Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular disease, including heart failure. Although linked to obesity and hypertension, its pathogenesis is multifactorial. Blunted postprandial sympathetic regulation of gut blood flow has been observed in overweight animals and suggested as a promotor of hypertension and LVH. We hypothesized that blunted postprandial superior mesenteric blood flow responses would be more common in overweight humans and associated with increased blood pressure and LVH. METHODS: Left ventricular dimensions and hemodynamic responses to a standardized high-calorie liquid meal were measured in healthy adolescents (n=82; 39 overweight/obese) by magnetic resonance imaging. Covariates such as body mass index, blood pressure, Tanner score, and an index of insulin resistance were included in multiple regression models to examine the independent associations of mesenteric flow response with blood pressure status and LVH. RESULTS: Food ingestion increased cardiac output (Δmean, 0.45 [SD, 0.62] L·min-1; P=3.8×10-8) and superior mesenteric artery flow (Δmean, 0.76 [SD, 0.35] L·min-1; P=4.2×10-31). A blunted mesenteric flow response was associated with increased left ventricular mass (B=-12.7 g·m-2.7 per L·min-1·m-0.92; P=6×10-5) and concentric LVH (log likelihood, -9.9; P=0.001), independently of known determinants of LVH, including body mass index. It was also associated with elevated systolic blood pressure (B=-18.0 mm Hg per L·min-1·m-0.92; P=0.001), but this link did not explain the association with left ventricular mass. CONCLUSIONS: Postprandial mesenteric vascular dysfunction is associated with LVH and hypertension, independently of common risk factors for those conditions. These findings highlight a new, independent marker of cardiovascular risk in the young.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31709984

RESUMO

BACKGROUND: Medical therapy for angina guided by invasive coronary vascular function testing holds promise but the longer-term effects on quality of life and clinical events are unknown among patients without obstructive disease. METHODS: 151 angina patients with symptoms and/or signs of ischemia and no obstructive coronary artery disease (INOCA) were randomized to stratified medical therapy guided by an interventional diagnostic procedure (IDP) versus standard care (control group with blinded IDP results). The IDP-facilitated diagnosis (microvascular angina, vasospastic angina, both, neither) was linked to guideline-based management. Prespecified endpoints included 1-year patient reported outcome measures (Seattle Angina Questionnaire [SAQ], quality of life [EQ5D]) and major adverse cardiovascular events (all- cause mortality, myocardial infarction, unstable angina hospitalization/revascularization, heart failure hospitalization, cerebrovascular event) at subsequent follow-up. RESULTS: Between 11/2016-12/2017 151 INOCA patients were randomized (n=75 intervention group; n=76 control group). At 1 year, overall angina (SAQ summary score) improved in the intervention group by 27% (difference 13.6 units; 95% CI 7.3 to 19.9,P<0.001). Quality of life (EQ5D index) improved in the intervention group relative to the control group (mean difference 0.11 units [18%]; 0.03 to 0.19;p=0.010). After a median follow-up of 19 months (IQR 16, 22), MACE was similar between the groups occuring in 9 (12%) subjects in the intervention group and 8 (11%) in the control group (p=0.803). CONCLUSION: Stratified medical therapy in INOCA patients leads to marked and sustained angina improvement and better quality of life at 1 year following invasive coronary angiography.

6.
8.
PLoS Med ; 16(10): e1002945, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31622334

RESUMO

BACKGROUND: National guidelines in most countries set screening intervals for diabetic retinopathy (DR) that are insufficiently informed by contemporary incidence rates. This has unspecified implications for interval disease risks (IDs) of referable DR, disparities in ID between groups or individuals, time spent in referable state before screening (sojourn time), and workload. We explored the effect of various screening schedules on these outcomes and developed an open-access interactive policy tool informed by contemporary DR incidence rates. METHODS AND FINDINGS: Scottish Diabetic Retinopathy Screening Programme data from 1 January 2007 to 31 December 2016 were linked to diabetes registry data. This yielded 128,606 screening examinations in people with type 1 diabetes (T1D) and 1,384,360 examinations in people with type 2 diabetes (T2D). Among those with T1D, 47% of those without and 44% of those with referable DR were female, mean diabetes duration was 21 and 23 years, respectively, and mean age was 26 and 24 years, respectively. Among those with T2D, 44% of those without and 42% of those with referable DR were female, mean diabetes duration was 9 and 14 years, respectively, and mean age was 58 and 52 years, respectively. Individual probability of developing referable DR was estimated using a generalised linear model and was used to calculate the intervals needed to achieve various IDs across prior grade strata, or at the individual level, and the resultant workload and sojourn time. The current policy in Scotland-screening people with no or mild disease annually and moderate disease every 6 months-yielded large differences in ID by prior grade (13.2%, 3.6%, and 0.6% annually for moderate, mild, and no prior DR strata, respectively, in T1D) and diabetes type (2.4% in T1D and 0.6% in T2D overall). Maintaining these overall risks but equalising risk across prior grade strata would require extremely short intervals in those with moderate DR (1-2 months) and very long intervals in those with no prior DR (35-47 months), with little change in workload or average sojourn time. Changing to intervals of 12, 9, and 3 months in T1D and to 24, 9, and 3 months in T2D for no, mild, and moderate DR strata, respectively, would substantially reduce disparity in ID across strata and between diabetes types whilst reducing workload by 26% and increasing sojourn time by 2.3 months. Including clinical risk factor data gave a small but significant increment in prediction of referable DR beyond grade (increase in C-statistic of 0.013 in T1D and 0.016 in T2D, both p < 0.001). However, using this model to derive personalised intervals did not have substantial workload or sojourn time benefits over stratum-specific intervals. The main limitation is that the results are pertinent only to countries that share broadly similar rates of retinal disease and risk factor distributions to Scotland. CONCLUSIONS: Changing current policies could reduce disparities in ID and achieve substantial reductions in workload within the range of IDs likely to be deemed acceptable. Our tool should facilitate more rational policy setting for screening.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31607674

RESUMO

OBJECTIVES: This study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years. BACKGROUND: Greater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood. METHODS: Associations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences. RESULTS: Fat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p < 0.001), whereas fat mass was negatively associated with cIMT (difference: -0.0032; 95% CI: 0.004 to -0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor-associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor. CONCLUSIONS: Subtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures might be more appropriate for the identification of arterial disease before adulthood.

10.
BMJ ; 367: l5367, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594780

RESUMO

OBJECTIVE: To estimate the risk of acute myocardial infarction (AMI) or stroke in adults with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). DESIGN: Matched cohort study. SETTING: Population based, electronic primary healthcare databases before 31 December 2015 from four European countries: Italy (n=1 542 672), Netherlands (n=2 225 925), Spain (n=5 488 397), and UK (n=12 695 046). PARTICIPANTS: 120 795 adults with a recorded diagnosis of NAFLD or NASH and no other liver diseases, matched at time of NAFLD diagnosis (index date) by age, sex, practice site, and visit, recorded at six months before or after the date of diagnosis, with up to 100 patients without NAFLD or NASH in the same database. MAIN OUTCOME MEASURES: Primary outcome was incident fatal or non-fatal AMI and ischaemic or unspecified stroke. Hazard ratios were estimated using Cox models and pooled across databases by random effect meta-analyses. RESULTS: 120 795 patients with recorded NAFLD or NASH diagnoses were identified with mean follow-up 2.1-5.5 years. After adjustment for age and smoking the pooled hazard ratio for AMI was 1.17 (95% confidence interval 1.05 to 1.30; 1035 events in participants with NAFLD or NASH, 67 823 in matched controls). In a group with more complete data on risk factors (86 098 NAFLD and 4 664 988 matched controls), the hazard ratio for AMI after adjustment for systolic blood pressure, type 2 diabetes, total cholesterol level, statin use, and hypertension was 1.01 (0.91 to 1.12; 747 events in participants with NAFLD or NASH, 37 462 in matched controls). After adjustment for age and smoking status the pooled hazard ratio for stroke was 1.18 (1.11 to 1.24; 2187 events in participants with NAFLD or NASH, 134 001 in matched controls). In the group with more complete data on risk factors, the hazard ratio for stroke was 1.04 (0.99 to 1.09; 1666 events in participants with NAFLD, 83 882 in matched controls) after further adjustment for type 2 diabetes, systolic blood pressure, total cholesterol level, statin use, and hypertension. CONCLUSIONS: The diagnosis of NAFLD in current routine care of 17.7 million patient appears not to be associated with AMI or stroke risk after adjustment for established cardiovascular risk factors. Cardiovascular risk assessment in adults with a diagnosis of NAFLD is important but should be done in the same way as for the general population.


Assuntos
Hipertensão/epidemiologia , Fígado/patologia , Infarto do Miocárdio/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Fumar/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/fisiopatologia , Países Baixos/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Espanha/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia
11.
Am J Nephrol ; : 1-9, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31665726

RESUMO

BACKGROUND: Evidence is limited on ethnic differences in associations between kidney function markers and mortality or cardiovascular disease (CVD). METHODS: Baseline cross-sectional analysis and longitudinal follow-up study of a UK population-based cohort of 1,116 Europeans and 1,104 South Asians of predominantly Indian descent, age 52 ± 7 years at baseline (1988-1991). Kidney function was estimated using Cystatin C and creatinine-based chronic kidney disease (CKD) Epidemiology Collaboration estimated glomerular filtration rate (eGFR) equations, and urinary albumin-creatinine ratio (ACR). Mortality was captured at 27 years, and incident CVD at 22 years, from death certification, medical records and participant report. Longitudinal associations between eGFR/ACR and mortality/incident CVD were examined using Cox models. RESULTS: eGFRcys was lower and ACR higher in South Asians than Europeans. eGFRcys and -eGFRcreat were more strongly associated with outcomes in Europeans than South Asians. Conversely, associations between ACR and outcomes were greater in South Asians than Europeans, for example, for CVD mortality: HRs (95% CI) adjusted for CVD risk factors and ACR/eGFRcys as appropriate, p for ethnicity interaction: eGFRcys: Europeans: 0.76 (0.62-0.92), South Asians: 0.92 (0.78-1.07), p = 0.05, eGFRcreat: Europeans 0.81 (0.67-0.99), South Asians 1.18 (0.97-1.41), p = 0.002, ACR: -Europeans: 1.24 (1.08-1.42), South Asians: 1.39 (1.25-1.57), p= 0.23. Addition of all CKD measures to a standard CVD risk factor model modestly improved prediction capability in -Europeans; in South Asians only ACR contributed to improvement. CONCLUSIONS: Strong associations between ACR and outcomes in South Asians of predominantly Indian origin, and null associations for eGFRcys and eGFRcreat, suggest that ACR may have greater utility in CVD risk prediction in South Asians. Further work is needed to validate these -findings.

13.
CMAJ ; 191(35): E955-E961, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481423

RESUMO

BACKGROUND: The evolving clinical burden of limb loss secondary to diabetes and peripheral artery disease remains poorly characterized. We sought to examine secular trends in the rate of lower-extremity amputations related to diabetes, peripheral artery disease or both. METHODS: We included all individuals aged 40 years and older who underwent lower-extremity amputations related to diabetes or peripheral artery disease in Ontario, Canada (2005-2016). We identified patients and amputations through deterministic linkage of administrative health databases. Quarterly rates (per 100 000 individuals aged ≥ 40 yr) of any (major or minor) amputation and of major amputations alone were calculated. We used time-series analyses with exponential smoothing models to characterize secular trends and forecast 2 years forward in time. RESULTS: A total of 20 062 patients underwent any lower-extremity amputation, of which 12 786 (63.7%) underwent a major (above ankle) amputation. Diabetes was present in 81.8%, peripheral artery disease in 93.8%, and both diabetes and peripheral artery disease in 75.6%. The rate of any amputation initially declined from 9.88 to 8.62 per 100 000 between Q2 of 2005 and Q4 of 2010, but increased again by Q1 of 2016 to 10.0 per 100 000 (p = 0.003). We observed a significant increase in the rate of any amputation among patients with diabetes, peripheral artery disease, and both diabetes and peripheral artery disease. Major amputations did not significantly change among patients with diabetes, peripheral artery disease or both. INTERPRETATION: Lower-extremity amputations related to diabetes, peripheral artery disease or both have increased over the last decade. These data support renewed efforts to prevent and decrease the burden of limb loss.

15.
Lancet Diabetes Endocrinol ; 7(10): 776-785, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31422062

RESUMO

BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists differ in their structure and duration of action and have been studied in trials of varying sizes and with different patient populations, with inconsistent effects on cardiovascular outcomes reported. We aimed to synthesise the available evidence by doing a systematic review and meta-analysis of cardiovascular outcome trials of these drugs. METHODS: We searched MEDLINE (via PubMed) and the Cochrane Central Register of Controlled Trials for eligible placebo-controlled trials reporting major adverse cardiovascular events (MACE; ie, cardiovascular death, stroke, or myocardial infarction) up to June 15, 2019. We did a meta-analysis using a random-effects model to estimate overall hazard ratios (HRs) for MACE, its components, death from any cause, hospital admission for heart failure, kidney outcomes, and key safety outcomes (severe hypoglycaemia, pancreatitis, and pancreatic cancer). We also examined MACE in several subgroups based on patient characteristics (history of cardiovascular disease, BMI, age, baseline HbA1c, and baseline estimated glomerular filtration rate), trial duration, treatment dosing interval, and structural homology. FINDINGS: Of 27 publications screened, seven trials, with a combined total of 56 004 participants, were included: ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN-6 (semaglutide), EXSCEL (exenatide), Harmony Outcomes (albiglutide), REWIND (dulaglutide), and PIONEER 6 (oral semaglutide). Overall, GLP-1 receptor agonist treatment reduced MACE by 12% (HR 0·88, 95% CI 0·82-0·94; p<0·0001). There was no statistically significant heterogeneity across the subgroups examined. HRs were 0·88 (95% CI 0·81-0·96; p=0·003) for death from cardiovascular causes, 0·84 (0·76-0·93; p<0·0001) for fatal or non-fatal stroke, and 0·91 (0·84-1·00; p=0·043) for fatal or non-fatal myocardial infarction. GLP-1 receptor agonist treatment reduced all-cause mortality by 12% (0·88, 0·83-0·95; p=0·001), hospital admission for heart failure by 9% (0·91, 0·83-0·99; p=0·028), and a broad composite kidney outcome (development of new-onset macroalbuminuria, decline in estimated glomerular filtration rate [or increase in creatinine], progression to end-stage kidney disease, or death attributable to kidney causes) by 17% (0·83, 0·78-0·89; p<0·0001), mainly due to a reduction in urinary albumin excretion. There was no increase in risk of severe hypoglycaemia, pancreatitis, or pancreatic cancer. INTERPRETATION: Treatment with GLP-1 receptor agonists has beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes. FUNDING: None.

16.
Heart ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366573

RESUMO

BACKGROUND: There are known risk factors associated with the development of heart failure (HF), but it is not fully understood whether these differ by sex. OBJECTIVES: To investigate sex differences in risk factors for HF incidence and mortality. METHODS: 468 941 participants (55.9% women, age range 37-73 years) were included. Established CVD risk factors (hypertension, hypercholesterolaemia, diabetes type 1 and 2, adiposity, smoking, physical activity and poor diet) and novel risk factors (grip strength, fitness, TV viewing and sleep duration) were the exposures of interest. HF incidence and mortality were the outcomes. RESULTS: Over a mean follow-up of 9.0 years, 1812 participants developed HF and 763 died due to HF. Women with type 1 diabetes (T1DM), type 2 diabetes (T2DM), hypertension, hypercholesterolaemia, low levels of physical activity and fitness, low strength, high levels of TV viewing, sleep duration <7 hours/day, smokers; those who were underweight and who were obese, had high body surface area and those who drink >14 units of alcohol were at higher risk of HF incidence. However, in women T2DM, hypercholesterolaemia, >3 hours/day of TV and sleep <7 hours/day, low level of physical activity and high level of TV viewing were more strongly associated with HF incidence compared with men. CONCLUSION: Several modifiable risk factors (in particular diabetes) appear more strongly associated with HF in women compared with men. The relevance of these findings to HF characteristics and future outcomes needs to be established.

17.
Diabetes Obes Metab ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31379119

RESUMO

People with diabetes mellitus are at higher risk of ischaemic stroke and worse outcomes thereafter. However, whether it is better to prescribe intensive glucose-lowering treatment compared with conventional treatment in people with diabetes to prevent recurrent stroke is debated. It is also crucial to consider whether specific antidiabetic agents are more efficacious and safer than others for prevention of stroke. In this review, we provide an overview of the efficacy of intensive and conventional glucose-lowering treatment in post-stroke management. Our conclusion is that the overall evidence for a beneficial effect of intensive glycaemic control on risk of stroke is limited. We also discuss evidence from recent large clinical trials of thiazolidinediones and new antidiabetic medications, including dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose co-transporter-2 inhibitors. On the basis of the findings of these trials, our conclusion is that pioglitazone and the GLP-1RA class (other than short-acting lixisenatide) are likely to lessen the occurrence of cerebrovascular disease (by mechanisms not dependent on glucose-lowering per se), whereas there is no consistent evidence for other drug classes.

19.
Menopause ; 26(9): 1002-1009, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31453962

RESUMO

OBJECTIVE: We sought to examine the association of menopausal hot flashing with vascular reactivity in two different vascular beds in the same cohort of postmenopausal women and explore the relationship between hot flashing and cardiovascular disease (CVD) risk profile. METHODS: A cross-sectional study of 79 healthy postmenopausal women, 23 of whom have never had menopausal hot flashes and 56 of whom have reported hot flashes. Endothelial function at a microvascular level was measured with Laser Doppler Imaging with Iontophoresis which assesses the response to both acetylcholine (Ach, endothelium dependent) and sodium-nitroprusside (SNP, endothelium independent). Reactive Hyperemia Index (RHI) was measured with peripheral arterial tonometry as a marker of endothelial function mainly at a macrovascular level. Metabolic biomarkers including insulin sensitivity were assessed. RESULTS: Women with hot flashes had enhanced microvascular response to Ach by ∼30% (P = 0.04) and to SNP by ∼31% (P = 0.02), but lower RHI by ∼13% (P = 0.05) compared with women without flashes. Hot flashing was associated with enhanced response to SNP and lower RHI after adjustment for confounders and conventional CVD risk factors. Women with hot flashes were more insulin resistant than nonflashers (HOMAIR: 1.9 (1.2-2.6) vs 1.4 (0.8-1.9), P = 0.03). CONCLUSIONS: Our data support the association of hot flashing with greater insulin resistance and lower macrovascular response. The paradoxical enhanced microvascular response in hot flashers could be the result of the net effect of thermoregulatory and nonnitric oxide-related pathways rather than of endothelial integrity.

20.
Nat Commun ; 10(1): 3346, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431621

RESUMO

Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors of long-term mortality in the circulation of 44,168 individuals (age at baseline 18-109), of whom 5512 died during follow-up. We apply a stepwise (forward-backward) procedure based on meta-analysis results and identify 14 circulating biomarkers independently associating with all-cause mortality. Overall, these associations are similar in men and women and across different age strata. We subsequently show that the prediction accuracy of 5- and 10-year mortality based on a model containing the identified biomarkers and sex (C-statistic = 0.837 and 0.830, respectively) is better than that of a model containing conventional risk factors for mortality (C-statistic = 0.772 and 0.790, respectively). The use of the identified metabolic profile as a predictor of mortality or surrogate endpoint in clinical studies needs further investigation.

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