Major Cardiovascular Outcomes Research Articles

Legacy Effect in the Treatment of Hypertension: Persistent Cardiovascular Protection after Conclusion of Randomized Clinical Trials in Hypertension.

Essential hypertension is the main determinant of cardiovascular morbidity and mortality worldwide. During the last decades, several antihypertensive drug therapies have been introduced and tested in clinical trials, both as monotherapies and combination therapies. The current recommended therapeutic approaches effectively reduce the lifetime risk of experiencing major cardiovascular outcomes and disabling comorbidities, such as myocardial infarction, stroke, and congestive heart failure. On the basis of multiple proofs, antihypertensive therapy is currently recommended for improving event-free survival rate and quality of life in different clinical settings and conditions. At the same time, other cardiovascular drugs, including novel lipid-lowering, anti-platelet, and anti-coagulation agents, have been made available and also contribute to reduce the incidence of atherothrombotic diseases. Beyond the beneficial aspects obtained by pharmacological treatment of major cardiovascular risk factors and comorbidities, including hypertension, several aspects remain to be defined. One major limitation linked to randomized, controlled clinical trials is represented by the relatively short duration of the studies, which usually ranges between 1 and 5years. Whether antihypertensive therapy should be maintained for a longer time (after 5years) and whether this is supported by sufficient evidence of a persisting benefit is supported by limited post-trial observations but mostly by findings derived from large clinical registries. The so-called legacy effect in the treatment of hypertension, in which patients who are treated with a given antihypertensive therapy may derive a long-term benefit after discontinuation of therapy, has been recently proposed on the basis of accumulating evidence and, in particular, on the availability of long-term post-trial observations in randomized controlled clinical trials. In this review, we discuss the evidence witnessing a legacy effect of antihypertensive therapy and whether this supports sufficiently lifetime drug treatment of hypertension.

P1818Descending aortic thoracic diameter: a risk marker for major adverse cardiovascular outcomes in women

Abstract Background Thoracic aortic diameters have been associated with cardiovascular risk factors and atherosclerosis. However, limited evidence regarding the role of thoracic aortic diameters as risk markers for major cardiovascular outcomes among women and men exist. Purpose To evaluate the independent associations between crude and indexed ascending and descending aortic (AA and DA) diameters with major cardiovascular outcomes among women and men and to provide optimal cutoff values associated with increased cardiovascular risk. Methods and results 2178 women and men ≥55 years from the prospective population-based Rotterdam Study underwent multi-detector CT scan of thorax. Crude diameters of the AA and DA were measured and indexed by height, weight, body surface area (BSA) and body mass index (BMI). Incidence of stroke, coronary heart disease (CHD), heart failure (HF), cardiovascular and all-cause mortality were evaluated during 13 years of follow-up. Weight-, BSA-, or BMI-indexed AA diameters showed significant associations with total or cardiovascular mortality in both sexes and height-indexed values showed association with HF in women. Crude AA diameters were associated with stroke in men and HF in women. For DA, crude and almost all indexed diameters showed significant associations with either stroke, HF, cardiovascular or total mortality in women. Only weight-, BSA- and BMI-indexed values were associated with total mortality in men. For crude DA diameter, the risk for stroke increased significantly at the 75th percentile among men while the risks for HF and cardiovascular mortality increased at the 75th and 85th percentiles respectively in women. Conclusions Our study suggests a role for descending thoracic aortic diameter as a marker for increased cardiovascular risk, in particular for stroke, heart failure and cardiovascular mortality among women. The cut points for increased risk for several of cardiovascular outcomes were below the 95th percentile of the distribution of aortic diameters.

P639Benefits and safety of exercise training in patients with severe three coronary vessels disease

Abstract Background Coronary heart disease is the leading cause of death in the world. Nowadays, there are still patients with untreatable coronary obstructions and exercise therapy could be an option to improve their quality of life and probably diminish mortality. Cardiac rehabilitation programs are recommended worldwide due its effectiveness and safety. However very high risk patients are often not included. Purpose To evaluate the benefit and safety of exercise therapy as a part of a cardiac rehabilitation program in patients with untreatable severe coronary heart disease. Methods A cohort of patients with coronary heart disease included in a cardiac rehabilitation program were studied. Those with severe coronary heart disease (Syntax score ≥33, group A) were identified. Patients were stratified using clinical records and cardiopulmonary exercise testing. They trained for 30 minutes, five times a week of aerobic exercise (cycle ergometer) and this therapy was complemented with general strength, coordination, balance and flexibility maneuvers. After twenty exercise sessions, a second cardiopulmonary exercise test was performed. Symptom limited cardiopulmonary exercise testing was undertaken using a ramp Balke protocol and cardiopulmonary variables were recorded. These patients were compared with their counterparts without severe coronary heart disease (Control group, group B). Studied variables were presented as frequencies (%), mean (SD), median (range) as appropriate. Comparisons between groups were made using chi square or paired T test as needed. All p values <0.05 were considered stochastically significant. Results From a total of 546 patients, seventy-one had severe coronary heart disease (Syntax score ≥33). There were no significant differences between groups on change of METs value and number of sessions assisted. No major adverse cardiovascular outcome was observed. The percentage of exercise induced arrhythmias was 75% in very high risk group vs 76% in control group, (p>0.05). Results are shown in table 1. Table 1. Characteristics between groups Patients Group A (n=75) Group B (n=471) p value Assisted training sessions 15±7 14±6 ns Increment in MET (ml/kg/min) 1.32±1.34 1.35±1.56 ns Arrhythmias, n (%) 56 (75) 370 (76) ns Angor/ST depression, n (%) 11 (15) 15 (3) <0.01 Differences in workload (Watts) 20±13 22±13 ns Conclusion Exercise training could be performed in an effective and safe manner in patients with very high risk untreated coronary heart disease.

4113Glucose lowering drugs or strategies, major adverse cardiovascular events and heart failure outcomes, and association with weight loss - meta-analysis of large cardiovascular outcome trials

Abstract Background Glucose lowering drugs or strategies (GLDS) have varied effects on major adverse cardiovascular events (MACE) and heart failure (HF) in cardiovascular outcomes trials. Mechanisms driving cardiovascular risk reduction remain elusive. Methods We searched MEDLINE, PubMed, and meeting abstracts up to 11/21/2018 for large GLDS cardiovascular outcome trials (CVOTs) in patients with or at risk for type 2 diabetes. Primary endpoints of MACE and HF were evaluated with random effects risk ratios (RR) and explored by baseline CVD subgroups and meta-regression by weight change across treatment arms. Results In 27 GLDS CVOTs, a total 207,820 patients, median age 63 years, 64% male, 64% CVD and 11% with prior HF were studied over a mean 3.8 years with 20,118 (10%) patients having MACE and 7,212 (4%) a HF event. Compared with standard care, GLDS overall lowered MACE (RR 0.92, P<0.ehz745.01171) but not HF (RR 1.01, P=0.91). Across GLDS, the magnitude and directionality varied modestly for MACE RR (P-int=0.07) but markedly for HF (P-int<0.ehz745.01171). Meta-regression showed a change in HF RR by 6% (95% CI 3%-9%) per 1 kg weight gain/loss between treatment arms (P=0.0006; Figure). In 9 trials of GLDS that achieved marked weight loss (lifestyle, GLP1 agonists, SGLT2 inhibitors), MACE benefit was confined to patients with baseline CVD (RR 0.89 [0.84–0.95] versus without (RR 1.02 [0.91–1.15]; P-int=0.01) with consistent HF effect (RR 0.80 [0.72–0.88] vs RR 0.76 [0.56–1.03]; P-int=0.74). Heart Failure Risk and Changes in Weight Conclusion HF outcomes were improved with GLDS that lower weight. Among diabetes GLDS that lower weight, there was a robust risk reduction in atherothrombotic and heart failure events, with the MACE benefit confined to patients with established CVD. Acknowledgement/Funding Heart and Stroke Foundation

P796Intensive blood pressure treatment significantly increases visit-to-visit systolic blood pressure variability. A randomized clinical trial

Abstract Background Intensive blood pressure lowering is increasingly gaining attention. Besides higher baseline blood pressure, visit-to-visit variability has showed association with target organ damage and major adverse cardiovascular outcomes in multiple medical reports. Purpose Our aim was to assess the effect of intensive treatment on systolic blood pressure (SBP) visit-to-visit variability in the SPRINT trial population during follow-up. Methods We included 9068 SPRINT participants with 128139 repeated SBP measurements. Participants were randomly assigned to intensive (SBP <120 mmHg) vs standard treatment (SBP between 135–139 mmHg). The primary outcome was a composite outcome of myocardial infarction, other acute coronary syndromes, acute decompensated heart failure, stroke, and cardiovascular mortality. We calculated the coefficient of variation (CV) and standard deviation (SD), taking into account all SBP measurements prior to the SPRINT primary outcome. Comparison of CV between intensive and standard treatment in the total SPRINT population and among different subgroups was made. Results CVs in intensive treatment groups were higher in total population and in all groups under study (See table). While second and third CV quartile showed a larger tendency to increase the risk for the primary SPRINT outcome in the intensive treatment compared to the standard treatment group, fourth CV quartiles were significantly associated with increase in primary SPRINT outcome in both intensive and standard treatment groups. Coefficient of variation in SPRINT trial Group Intensive treatment Standard treatment Total population 9.80 (3.22)* 8.52 (2.96) Females 10.46 (3.29)* 9.18 (3.15) Black person 9.99 (3.38)* 8.82 (3.15) Prevalence CKD 10.14 (3.22)* 9.12 (3.06) Prevalence CVD 10.28 (3.32)* 8.93 (3.23) ≥75 year 10.40 (3.18)* 9.01 (3.07) SAEs 10.30 (3.39)* 9.08 (3.13) (CKD: chronic kidney disease; CVD: cardiovascular disease; SAEs: serious adverse events. *P<0.05). Conclusions Intensive blood pressure treatment significantly increases SBP visit-to-visit variability in total SPRINT population and in all subgroups under study. Additional longitudinal studies with long-term follow-up are warranted to evaluate the impact of increases in SBP visit-to-visit variability due to intensive treatment on risk of major cardiovascular events.

P1249Prognostic impact of sarcopenia on major adverse cardiovascular outcomes in coronary artery disease patients undergoing successful percutaneous coronary intervention

Abstract Background Sarcopenia is an emerging marker of frailty. Its prognostic impact on atherosclerotic cardiovascular disease (ASCVD) requires further investigation. Purpose We investigated the long-term prognostic impact of computed tomography (CT)-determined sarcopenia in patients with coronary artery disease (CAD). Methods Total 475 CAD patients those who underwent successful percutaneous coronary intervention (PCI) and performed CT scan within 30 days of PCI were enrolled. The cross-sectional area of skeletal muscle at the first lumbar vertebra (L1) level was measured. Sarcopenia was defined as L1 skeletal muscle index of less than 34.60 cm2/m2 for men and of less than 25.90 cm2/m2 for women. Primary outcome was 3-year all-cause mortality and secondary outcome was 3-year major adverse cardiovascular event (MACE), a composite of all-cause mortality, any myocardial infarction, and repeat revascularization. Results Sarcopenia was present in 214 (45.1%) of 475 patients. The incidence of 3-year all-cause mortality and MACE was significantly higher in patients with sarcopenia than in those without sarcopenia (17.7% vs. 5.7%, p<0.001; and 35.0% vs. 11.2%, p<0.001, respectively). In the fully adjusted multivariable analysis, sarcopenia was an independent predictor of higher risk of 3-year all-cause mortality (odds ratio [OR]: 2.98; 95% confidence interval [CI]: 1.35 to 6.58, p=0.007) and MACE (OR: 4.39; 95% CI: 2.49 to 7.73, p<0.001). The results were consistent after propensity-score matched analysis with 100 pairs of study population (C-statistics = 0.868). Kaplan–Meier analysis of 3-year outcomes Overall population PSM population Sarcopenia (n=214) No sarcopenia (n=261) Log-rank p-value Sarcopenia (n=100) No sarcopenia (n=100) Log-rank p-value All-cause mortality 36 (17.7) 14 (5.7) <0.001 19 (20.0) 7 (7.7) 0.013 Non-fatal MI 12 (6.6) 5 (2.0) 0.021 6 (7.0) 2 (2.3) 0.134 Repeat revascularization 32 (20.3) 14 (6.2) <0.001 17 (23.3) 8 (8.0) 0.027 Total MACEs 68 (35.0) 27 (11.2) <0.001 36 (39.3) 14 (15.4) 0.001 Data are expressed as n (%). MACE = major adverse cardiovascular event; MI = myocardial infarction; PSM = propensity-score matched. Clinical impact of sarcopenia on CAD Conclusion Sarcopenia is a useful predictor of adverse clinical outcomes in patients with CAD undergoing PCI. CT-determined sarcopenia may further aid in risk stratification and decision-making for patients with established ASCVD. Acknowledgement/Funding National Research Foundation of Korea (NRF-2016R1A2B3013825), Ministry of Future Creation and Science of Korea (2018K000255)

P1584The prognostic significance of the blood pressure-pulse wave velocity association for cardiovascular outcomes and mortality in hemodialysis patients

Abstract Introduction and purpose Hemodialysis patients have premature arterial stiffness, and the relationship between pulse wave velocity (PWV) and blood pressure (BP) may be different than in other hypertensives. Previous studies showed that when BP decrease is accompanied by PWV decrease the survival is improved. The aim of this study is to examine the prognostic significance of BP sensitivity of PWV for major cardiovascular outcomes and all-cause mortality in hemodialysis patients. Methods This is a prospective cohort study including 242 hemodialysis patients [age, 62.6±14.2 years; female, 91 (37.6%); hemodialysis vintage, 41.53±43.46]. All subjects underwent 48-hour-ABPM with Mobil-O-Graph-NG and followed-up for 33.17±19.68 months. The within-individual MBP-PWV association (MBP, dependent and PWV independent variable) was evaluated using the beta-coefficient value from simple linear regression analysis for each patient. The primary end-point was first occurrence of all-cause death, non-fatal myocardial infarction or non-fatal stroke. Secondary end-points were: (i) all-cause mortality; (ii) cardiovascular mortality; (iii) a combination of cardiovascular events. Results Patients who experienced the primary end-point during follow-up had significantly lower beta-coefficient levels (primary end-point: 19.877±3.975 vs 18.483±3.550, p=0.008). Higher quartiles of beta-coefficients (indicating dependency of PWV on MBP) were associated with higher cumulative freedom from the primary end-point (50.8%, 60.0%, 70.0% and 80.3% for quartiles 1 to 4 respectively; logrank-p=0.001), higher overall survival (60.7%, 61.7%, 73.3%, 86.9%; logrank-p=0.002) and higher cardiovascular survival (78.7%, 75.0%, 81.7%, 91.8% for quartiles 1 to 4; logrank-p=0.044). The future risk for the primary end-point, all-cause and cardiovascular mortality and the combined outcome was progressively increasing for lower quartiles of beta-coefficients (HR for all-cause mortality 3.395; 95% CI: 1.524–7.563, p=0.003 for quartile 1 vs quartile 4). Age (OR: 1.046, 95% CI: 1.016–1.077 per year increase, p=0.003) and 48h heart rate (OR: 0.949, 95% CI: 0.916–0.982 per bpm increase, p=0.003) were independently associated with weaker relationship between 48h-MBP and 48h-PWV. Conclusions Lower within-individual MBP-PWV association, based on AMBP recordings, is associated with higher risk of death and cardiovascular events in hemodialysis. These findings support that BP-independent arterial stiffness may be the underlying factor for adverse outcomes in these individuals.

Impact of Dual versus Single Antiplatelet Therapy on Major Cardiovascular Outcomes in Patients with Acute Coronary Syndrome in the Arabian Gulf

Objective: To evaluate the association of dual versus single antiplatelet therapy with major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) in the Arabian Gulf. Subjects and Methods: Data were analyzed from 3,559 patients with a diagnosis of ACS admitted to 29 hospitals in 4 Arabian Gulf countries (Bahrain, Kuwait, Oman, and United Arab Emirates) from January 2012 to January 2013. Dual antiplatelet therapy (DAPT), consisting of aspirin and clopidogrel, was compared to aspirin alone. MACE included 12-months cumulative stroke/transient ischemic attack (TIA), myocardial infarction (MI), all-cause mortality, and readmissions for cardiac reasons, post discharge. Analyses were performed using multivariable logistic regression. Results: A total of 74% (n = 2,634) of the patients were on DAPT. At 12-month follow-up, patients on DAPT were significantly less likely to experience MACE events (adjusted OR [aOR] 0.73; 95% CI: 0.61–0.86; p < 0.001). Lower cardiovascular (CV) event rates were also consistent across the following MACE components; MI (aOR 0.66; 95% CI: 0.49–0.88; p = 0.005), all-cause mortality (aOR 0.69; 95% CI: 0.51–0.94; p = 0.018), and readmissions for cardiac reasons (aOR 0.79; 95% CI: 0.66–0.95; p = 0.011). Conversely, DAPT was adversely associated with increased risk of stroke/TIA (aOR 1.68; 95% CI: 1.05–2.69; p = 0.030). Conclusions: DAPT, compared to aspirin therapy alone, was generally associated with better CV outcomes after an ACS event. However, DAPT was adversely associated with increased risk of stroke/TIA in ACS patients in the Arabian Gulf.

Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes

Type 2 diabetes is associated with increased cardiovascular risk. In placebo-controlled cardiovascular safety trials, the dipeptidyl peptidase-4 inhibitor linagliptin demonstrated noninferiority, but it has not been tested against an active comparator. This trial assessed cardiovascular outcomes of linagliptin vs glimepiride (sulfonylurea) in patients with relatively early type 2 diabetes and risk factors for or established atherosclerotic cardiovascular disease. Randomized, double-blind, active-controlled, noninferiority trial, with participant screening from November 2010 to December 2012, conducted at 607 hospital and primary care sites in 43 countries involving 6042 participants. Adults with type 2 diabetes, glycated hemoglobin of 6.5% to 8.5%, and elevated cardiovascular risk were eligible for inclusion. Elevated cardiovascular risk was defined as documented atherosclerotic cardiovascular disease, multiple cardiovascular risk factors, aged at least 70 years, and evidence of microvascular complications. Follow-up ended in August 2018. Patients were randomized to receive 5 mg of linagliptin once daily (n = 3023) or 1 to 4 mg of glimepiride once daily (n = 3010) in addition to usual care. Investigators were encouraged to intensify glycemic treatment, primarily by adding or adjusting metformin, α-glucosidase inhibitors, thiazolidinediones, or insulin, according to clinical need. The primary outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke with the aim to establish noninferiority of linagliptin vs glimepiride, defined by the upper limit of the 2-sided 95.47% CI for the hazard ratio (HR) of linagliptin relative to glimepiride of less than 1.3. Of 6042 participants randomized, 6033 (mean age, 64.0 years; 2414 [39.9%] women; mean glycated hemoglobin, 7.2%; median duration of diabetes, 6.3 years; 42% with macrovascular disease; 59% had undergone metformin monotherapy) were treated and analyzed. The median duration of follow-up was 6.3 years. The primary outcome occurred in 356 of 3023 participants (11.8%) in the linagliptin group and 362 of 3010 (12.0%) in the glimepiride group (HR, 0.98 [95.47% CI, 0.84-1.14]; P < .001 for noninferiority), meeting the noninferiority criterion but not superiority (P = .76). Adverse events occurred in 2822 participants (93.4%) in the linagliptin group and 2856 (94.9%) in the glimepiride group, with 15 participants (0.5%) in the linagliptin group vs 16 (0.5%) in the glimepiride group with adjudicated-confirmed acute pancreatitis. At least 1 episode of hypoglycemic adverse events occurred in 320 (10.6%) participants in the linagliptin group and 1132 (37.7%) in the glimepiride group (HR, 0.23 [95% CI, 0.21-0.26]). Among adults with relatively early type 2 diabetes and elevated cardiovascular risk, the use of linagliptin compared with glimepiride over a median 6.3 years resulted in a noninferior risk of a composite cardiovascular outcome. ClinicalTrials.gov Identifier: NCT01243424.

SGLT2 inhibitor or GLP-1 receptor agonist in type 2 diabetes?

Among the newest glucose-lowering agents for the treatment of type 2 diabetes, two classes raise much interest: glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Indeed, both showed a cardiovascular protection in dedicated outcome studies in patients with type 2 diabetes at high cardiovascular risk. 1 Scheen AJ Cardiovascular outcome studies in type 2 diabetes: comparison between SGLT2 inhibitors and GLP-1 receptor agonists. Diabetes Res Clin Pract. 2018; 143: 88-100 Summary Full Text Full Text PDF PubMed Scopus (35) Google Scholar , 2 Zelniker TA Wiviott SD Raz I et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019; 139: 2022-2031 Crossref PubMed Scopus (273) Google Scholar These findings had a major effect on the newer guidelines for the management of type 2 diabetes. In patients with atherosclerotic cardiovascular disease, guidelines now recommend, after failure of metformin monotherapy, the addition of a GLP-1 receptor agonist or an SGLT2 inhibitor that was shown to reduce the risk of major cardiovascular events. 3 Davies MJ D'Alessio DA Fradkin J et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018; 61: 2461-2498 Crossref PubMed Scopus (604) Google Scholar In the absence of heart failure or renal disease, two conditions in which SGLT2 inhibitors appear more protective, 2 Zelniker TA Wiviott SD Raz I et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019; 139: 2022-2031 Crossref PubMed Scopus (273) Google Scholar the clinician can choose between these two pharmacological options without specific guidance in the absence of comparative trials. 3 Davies MJ D'Alessio DA Fradkin J et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018; 61: 2461-2498 Crossref PubMed Scopus (604) Google Scholar Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trialOnce-weekly semaglutide 1·0 mg was superior to daily canagliflozin 300 mg in reducing HbA1c and bodyweight in patients with type 2 diabetes uncontrolled on metformin therapy. These outcomes might guide treatment intensification choices. Full-Text PDF

Impact of Discrepancies in General and Abdominal Obesity on Major Adverse Cardiac Events.

BackgroundBody mass index and waist circumference (WC) are commonly used metrics that reflect general obesity and abdominal obesity. However, the impact of general and abdominal obesity discrepancies on the risk for major adverse cardiac events (MACE) is less explored.Methods and ResultsThe study population was derived from the Korean National Health Insurance Service‐Health Screening Cohort. Among 315 982 participants aged 40 years or older who underwent health examinations between 2008 and 2009, body mass index and WC were used to determine the obesity status. The participants were followed from January 1, 2010 for MACE until December 31, 2015. Cox proportional hazards models were used to evaluate the association of obesity and the risk of MACE. Compared with men who were not obese, those with abdominal obesity without general obesity (adjusted hazard ratio (aHR) 1.29, 95% CI 1.16–1.43), and general and abdominal obesity (aHR 1.20, 95% CI 1.12–1.29) had elevated risk of MACE, while those with general obesity without abdominal obesity (aHR 1.06, 95% CI 0.98–1.16) did not. Similarly, women with abdominal obesity without general obesity (aHR 1.13, 95% CI 1.03–1.24) and those with general and abdominal obesity (aHR 1.15, 95% CI 1.06–1.25) had increased risk of MACE, while those with general obesity without abdominal obesity (aHR 1.07, 95% CI 0.88–1.30) did not.ConclusionsAbdominal obesity without general obesity was associated with an elevated risk of major cardiovascular outcomes while general obesity without abdominal obesity did not. Concurrent determination of body mass index and WC may be beneficial for the accurate determination of future cardiovascular risk.

Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity

Although metabolic surgery (defined as procedures that influence metabolism by inducing weight loss and altering gastrointestinal physiology) significantly improves cardiometabolic risk factors, the effect on cardiovascular outcomes has been less well characterized. To investigate the relationship between metabolic surgery and incident major adverse cardiovascular events (MACE) in patients with type 2 diabetes and obesity. Of 287 438 adult patients with diabetes in the Cleveland Clinic Health System in the United States between 1998 and 2017, 2287 patients underwent metabolic surgery. In this retrospective cohort study, these patients were matched 1:5 to nonsurgical patients with diabetes and obesity (body mass index [BMI] ≥30), resulting in 11 435 control patients, with follow-up through December 2018. Metabolic gastrointestinal surgical procedures vs usual care for type 2 diabetes and obesity. The primary outcome was the incidence of extended MACE (composite of 6 outcomes), defined as first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation. Secondary end points included 3-component MACE (myocardial infarction, ischemic stroke, and mortality) and the 6 individual components of the primary end point. Among the 13 722 study participants, the distribution of baseline covariates was balanced between the surgical group and the nonsurgical group, including female sex (65.5% vs 64.2%), median age (52.5 vs 54.8 years), BMI (45.1 vs 42.6), and glycated hemoglobin level (7.1% vs 7.1%). The overall median follow-up duration was 3.9 years (interquartile range, 1.9-6.1 years). At the end of the study period, 385 patients in the surgical group and 3243 patients in the nonsurgical group experienced a primary end point (cumulative incidence at 8-years, 30.8% [95% CI, 27.6%-34.0%] in the surgical group and 47.7% [95% CI, 46.1%-49.2%] in the nonsurgical group [P < .001]; absolute 8-year risk difference [ARD], 16.9% [95% CI, 13.1%-20.4%]; adjusted hazard ratio [HR], 0.61 [95% CI, 0.55-0.69]). All 7 prespecified secondary outcomes showed statistically significant differences in favor of metabolic surgery, including mortality. All-cause mortality occurred in 112 patients in the metabolic surgery group and 1111 patients in the nonsurgical group (cumulative incidence at 8 years, 10.0% [95% CI, 7.8%-12.2%] and 17.8% [95% CI, 16.6%-19.0%]; ARD, 7.8% [95% CI, 5.1%-10.2%]; adjusted HR, 0.59 [95% CI, 0.48-0.72]). Among patients with type 2 diabetes and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MACE. The findings from this observational study must be confirmed in randomized clinical trials. ClinicalTrials.gov Identifier: NCT03955952.

Neutrophil-to-Lymphocyte Ratio Predicts Contrast-Induced Acute Kidney Injury in Patients with ST-Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention

Background: Development of contrast-induced acute kidney injury (CI-AKI) in patients with ST-elevation myocardial infarction (STEMI) treated via primary percutaneous coronary intervention (PCI) is a major cause of morbidity and mortality worldwide. The neutrophil-to-lymphocyte ratio (NLR), which is a marker of inflammation, has been demonstrated to be associated with the development of major adverse cardiovascular outcomes in many studies. From this point of view, in this study, we aimed to evaluate the predictive value of the NLR as regards the occurrence of CI-AKI in patients with STEMI undergoing primary PCI. Methods: This study was conducted at Dr. Siyami Ersek Training and Research Hospital from May 2008 to June 2016. A total of 2000 patients with STEMI treated via primary PCI were enrolled in the study. The NLR was calculated as the ratio of the number of neutrophils to the number of lymphocytes. All venous blood samples were obtained within 8 hours after admission. CI-AKI was the primary end point of the study. Then, the relationship between CI-AKI and the NLR was assessed. Results: CI-AKI was detected in 148 (7.4%) patients. The patients who developed CI-AKI had a significantly higher NLR than those who did not (7.08±4.43 vs. 6.18±3.98; P=0.011). In the multivariate logistic regression analyses, the NLR remained a significant independent predictor of CI-AKI (OR: 1.78, 95% CI: 1.21-2.61, and P=0.003). Conclusion: The NLR may be a significant independent predictor of CI-AKI in patients with STEMI treated via primary PCI and higher NLR values could be independently associated with a greater risk for CI-AKI.

Dexmedetomidine for the prevention of postoperative delirium in elderly patients undergoing noncardiac surgery: A meta-analysis of randomized controlled trials.

BackgroundPostoperative delirium (POD) among the elderly population that undergoes noncardiac surgery is significantly associated with adverse clinical outcomes. We conducted this meta-analysis to evaluate the effectiveness and safety of dexmedetomidine for the prophylaxis of POD among the elderly population after noncardiac surgery.MethodsWe searched Embase, PubMed, and the Cochrane Library from inception date to March 2019 for randomized controlled trials (RCTs) that compared dexmedetomidine and placebo for the prevention of POD and evaluated the major cardiovascular outcomes among elderly people after noncardiac surgery. Two authors independently screened the studies and extracted data from the published articles. The main outcome was the incidence of POD. The secondary outcomes included the occurrence of bradycardia, hypotension, hypertension, tachycardia, myocardial infarction, stroke, hypoxaemia, and all-cause mortality.ResultsA total of 6 RCTs with 2102 participants were included. Compared with placebo, dexmedetomidine significantly reduced the prevalence of POD (RR = 0.61, 95% CI 0.34–0.76, P = 0.001, I2 = 66%), and the risk of tachycardia (RR = 0.48, 95% CI 0.30–0.76, P = 0.002, I2 = 0%), hypertension (RR = 0.59, 95% CI 0.44–0.79, P < 0.001, I2 = 20%), stroke (RR = 0.22, 95% CI 0.06–0.76, P = 0.02, I2 = 0%), and hypoxaemia (RR = 0.50, 95% CI 0.32–0.78, P = 0.002, I2 = 0%) in elderly patients who underwent noncardiac surgery. However, dexmedetomidine accelerated the occurrence of bradycardia (RR = 1.36, 95% CI 1.11–1.67, P = 0.003, I2 = 0%). Furthermore, no significant differences were observed in the incidence of hypotension, myocardial infarction, and all-cause mortality between the dexmedetomidine and placebo groups.ConclusionsAmong elderly patients after noncardiac surgery, the prophylactic use of dexmedetomidine, compared with the use of placebo, was related to a decline in the incidence of POD.

Minireview: are SGLT2 inhibitors heart savers in diabetes?

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a class of drugs that promote urinary glucose excretion in the treatment of diabetes, have provoked large interest of scientific and professional community due to their positive and, somehow, unexpected results in the three major cardiovascular outcome trials (EMPA-REG OUTCOME trial with empagliflozin, CANVAS Program with canagliflozin, and DECLARE-TIMI 58 with dapagliflozin). In fact, along with the reduction of major adverse cardiovascular events, SGLT2 inhibitors reduced significantly hospitalization for heart failure regardless of existing atherosclerotic cardiovascular disease or a history of heart failure. The latter have reminded us of the frequent but neglected entity of diabetic cardiomyopathy which is currently poorly understood despite its great clinical importance. Physiological mechanisms responsible for the benefits of SGLT2 inhibitors are complex and multifactorial and still not well defined. Interestingly, the time frame of their effect excludes a glucose- and antiatherosclerotic-mediated effect. It would be of great importance to better understand SGLT2 inhibitor mechanisms of action since they could have a potential to be used in early stages of diabetes as cardioprotective agents. There are widely available biomarkers as well as echocardiography that are used in everyday clinical practice and could elucidate physiological mechanisms in the heart protection with SGLT2 inhibitors treatment but studies are still lacking. The purpose of this minireview is to summarize the latest concepts about SGLT2 inhibitors and its benefits regarding diabetic cardiomyopathy especially on its early stage development and to discuss controversies and potential future developments in the field.

Cardiovascular safety of tocilizumab: A systematic review and network meta-analysis.

ObjectivesOur objective was to compare the cardiovascular safety of tocilizumab and other biological disease-modifying antirheumatic drugs (bDMARD) in rheumatoid arthritis using a network meta-analysis (NMA).MethodsA systematic literature search through May 2018 identified randomized controlled trials (RCT) or observational studies (cohort only) reporting cardiovascular outcomes of tocilizumab (TCZ) and/or abatacept (ABA) and/or rituximab (RTX) and/or tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis patients. The composite primary outcome was the rate of major adverse cardiovascular outcomes (MACE, myocardial infarction (MI), peripheral artery disease (PAD) and cardiac heart failure (CHF)).Results19 studies were included in the NMA, including 11 RCTs and 8 cohort studies. We found less events with RTX (5.41 [1.70;17.26]. We found no difference between TCZ and other treatments. Concerning MI, we found no difference between TCZ and csDMARD (4.23 [0.22;80.64]), no difference between TCZ and TNFi (2.00 [0.18;21.84]). There was no difference between TCZ and csDMARD (1.51[0.02;103.50] and between TCZ and TNFi (1.00 [0.06;15.85]) for stroke event.With cohorts and RCT NMA, we found no difference between TCZ and other treatments for MACE (0.66 [0.42;1.03] with ABA, 1.04 [0.60;1.81] with RTX, 0.78[0.53;1.16] and 0.91 [0.54;1.51] with csDMARD), but the risk of myocardial infarction was lower with TCZ compared to ABA (0.67 [0.47;0.97]).We lacked data to compare TCZ and other bDMARD for stoke and MI. Not enough data was available to perform a NMA for CHF and PAD.ConclusionsDespite an increase in cholesterol levels, TCZ has safe cardiovascular outcomes compared to other bDMARD.

Long-term follow-up of intensive glycaemic control in type 2 diabetes

In a 15-year follow-up of the VADT study, no differences in major cardiovascular outcomes were found among individuals with type 2 diabetes mellitus who underwent either intensive or standard glucose control. These results indicate that intensification of glycaemic control might not be expected to mitigate the risk of cardiovascular events.

Glucagon-Like Peptide-1 Receptor Analogues in Type 2 Diabetes: Their Use and Differential Features.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are well established as effective adjuncts to lifestyle modification in the treatment of type 2 diabetes (T2D) as monotherapy or in combination with oral glucose-lowering drugs ± insulin. The six subcutaneous GLP-1RA formulations (i.e. twice-daily exenatide, once-daily liraglutide and lixisenatide, and once-weekly dulaglutide, exenatide and semaglutide) currently available in the EU and USA have many similarities, but also some unique features and properties. By stimulating GLP-1 receptors, GLP-1RAs increase insulin secretion and suppress glucagon release in a glucose-dependent manner, thereby improving clinical and patient-reported outcomes related to glycaemic control and weight. They also have been shown to reduce, or at least not increase, the risk of major cardiovascular outcomes. GLP-1RAs are generally well tolerated, with gastrointestinal and injection-site reactions being the most troublesome drug-related adverse events, and are associated with a very low intrinsic risk of hypoglycaemia. Treatment with GLP-1RAs should be customized to meet the clinical needs and personal preferences of the individual.

Microvascular Complications Burden Affects Risk of Major Vascular Events and All-Cause Mortality in Type 1 Diabetes: A 10-Year Follow-Up Study

Background: To which extent the presence of one or more microvascular complication (MC) affects cardiovascular (CV) outcomes and mortality in diabetes is still debated. We evaluated the relationship between MC and incidence of major CV events and all-cause mortality in type 1 diabetes. Methods: We recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10*8±2*5 years. Hazard Ratios (HR) for outcomes were determined by unadjusted and adjusted Cox regressions. Findings: Out of 774 individuals, 54·9% had no-MC, 32·3% 1 MC, 9·7% 2 MC and 3·1% 3 MC. A total of 54 deaths occurred. Death rate increased from no-MC 2·1% (Ref) to 1-MC 7·2% (HR 3·54 [95% CI 1·59–7·87]), 2-MC 14·7% (6·41 [2·65–15·49]) and 3-MC 66·7% (41·73 [18·42–94·57]; p<0·0001). After adjustments, HRs were: 1-MC 2·05 (0·88–4·76), 2-MC 1·98 (0·75–5·21), 3-MC 7·02 (2·44–20·20; p=0·002). Forty-nine subjects had at least one CV event, and cumulative incidence went from no-MC 2·2% (Ref) to 1-MC 5·0%; (2·27 [0·95–5·38]), 2-MC 26·8% (12·88 [5·82–28·50]) and 3-MC 40·9% (29·34 [11·59–74·25]; p<0·0001). Upon adjustments, HRs were: 1-MC 1·59 (0·65–3·88), 2-MC 4·33 (1·75–10·74), 3-MC 9·31 (3·18–27·25; p<0·0001). Thirty-five individuals had at least one coronary event, which cumulative incidence increased with MC burden (p<0·0001). Interpretation: In type 1 diabetes, MC burden increases in an independent dose-dependent manner the risk of major CV outcomes and all-cause mortality. The presence and number of MC should be considered in stratifying overall CV risk in type 1 diabetes. Funding Statement: This work was supported by a grant from the Regione Toscana, Italy. (December 19, 2011), ID number D55E11002680005. Declaration of Interests: MG has received travel grants from AstraZeneca and Novo Nordisk. MA has received speaker/advisory honoraria from Abbott Laboratories. FC has received travel grants from Novo Nordisk. GD reports past participation in advisory boards from AstraZeneca, Eli Lilly and Co and Novartis Pharmaceuticals. SDP reports past participation in advisory boards and/or receiving research grants from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Co, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk, Sanofi, Servier, and Takeda Pharmaceuticals. GP has received travel grants and speaker/advisory honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Co, Merck Sharp & Dohme, Mundipharma Pharmaceuticals, Novo Nordisk, and Takeda Pharmaceuticals. All other authors (EG, RG, DL, MR, and PF) declare no competing interests. Ethics Approval Statement: The Ethics Committee of the University of Pisa approved the study protocol, consent procedures and data analysis plan.

Association between diabetes mellitus and the risk for major cardiovascular outcomes and all-cause mortality in women compared with men: a meta-analysis of prospective cohort studies

ObjectivePrevious studies have reported sex differences in associations between diabetes mellitus (DM) and the risk of developing coronary heart disease (CHD) and stroke; however, the risk for cardiac death and...