The author examines the ability of left atrial size and function to predict cardiovascular outcomes. Data are sufficient to recommend evaluation of left atrial volume in certain populations, and ...although analysis of atrial reservoir, conduit, and booster pump function trails in that regard, the gap is rapidly closing. In this state-of-the-art paper, the author reviews the methods used to assess left atrial size and function and discusses their role in predicting cardiovascular events in general and referral populations and in patients with atrial fibrillation, cardiomyopathy, ischemic heart disease, and valvular heart disease.
Summary
The publication of “The Sleep Apnea Syndromes” by Guilleminault et al. in the 1970s hallmarked the discovery of a new disease entity involving serious health consequences. Obstructive sleep ...apnea was shown to be the most important disorder among the sleep apnea syndromes (SAS). In the course of time, it was found that the prevalence of obstructive sleep apnea reached the proportions of a global epidemic, with a major impact on public health, safety and the economy. Early on, a metric was introduced to gauge the seriousness of obstructive sleep apnea, based on the objective measurement of respiratory events during nocturnal sleep. The apnea index and later on the apnea−hypopnea index, being the total count of overnight respiratory events divided by the total sleep time in hours, were embraced as principle measures to establish the diagnosis of obstructive sleep apnea and to rate its severity. The current review summarises the historical evolution of the apnea−hypopnea index, which has been subject to many changes, and has been criticised for not capturing relevant clinical features of obstructive sleep apnea. In fact, the application of the apnea−hypopnea index as a continuous exposure variable is based on assumptions that it represents a disease state of obstructive sleep apnea and that evocative clinical manifestations are invariably caused by obstructive sleep apnea if the apnea−hypopnea index is above diagnostic threshold. A critical appraisal of the extensive literature shows that both assumptions are invalid. This conclusion prompts a reconsideration of the role of the apnea−hypopnea index as the prime diagnostic metric of clinically relevant obstructive sleep apnea.
Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), many of whom do not report daytime sleepiness. First-line treatment for symptomatic OSA is continuous positive ...airway pressure (CPAP), but its value in patients without daytime sleepiness is uncertain.
To determine the effects of CPAP on long-term adverse cardiovascular outcome risk in patients with CAD with nonsleepy OSA.
This single-center, prospective, randomized, controlled, open-label, blinded evaluation trial was conducted between December 2005 and November 2010. Consecutive patients with newly revascularized CAD and OSA (apnea-hypopnea index ≥15/h) without daytime sleepiness (Epworth Sleepiness Scale score <10) were randomized to auto-titrating CPAP (n = 122) or no positive airway pressure (n = 122).
The primary endpoint was the first event of repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality. Median follow-up was 57 months. The incidence of the primary endpoint did not differ significantly in patients who did versus did not receive CPAP (18.1% vs. 22.1%; hazard ratio, 0.80; 95% confidence interval, 0.46-1.41; P = 0.449). Adjusted on-treatment analysis showed a significant cardiovascular risk reduction in those who used CPAP for ≥4 versus <4 hours per night or did not receive treatment (hazard ratio, 0.29; 95% confidence interval, 0.10-0.86; P = 0.026).
Routine prescription of CPAP to patients with CAD with nonsleepy OSA did not significantly reduce long-term adverse cardiovascular outcomes in the intention-to-treat population. There was a significant reduction after adjustment for baseline comorbidities and compliance with the treatment. Clinical trial registered with www.clinicaltrials.gov (NCT 00519597).
Myocardial perfusion reflects the macro- and microvascular coronary circulation. Recent quantitation developments using cardiovascular magnetic resonance perfusion permit automated measurement ...clinically. We explored the prognostic significance of stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR, the ratio of stress to rest MBF).
A 2-center study of patients with both suspected and known coronary artery disease referred clinically for perfusion assessment. Image analysis was performed automatically using a novel artificial intelligence approach deriving global and regional stress and rest MBF and MPR. Cox proportional hazard models adjusting for comorbidities and cardiovascular magnetic resonance parameters sought associations of stress MBF and MPR with death and major adverse cardiovascular events (MACE), including myocardial infarction, stroke, heart failure hospitalization, late (>90 day) revascularization, and death.
A total of 1049 patients were included with a median follow-up of 605 (interquartile range, 464-814) days. There were 42 (4.0%) deaths and 188 MACE in 174 (16.6%) patients. Stress MBF and MPR were independently associated with both death and MACE. For each 1 mL·g
·min
decrease in stress MBF, the adjusted hazard ratios for death and MACE were 1.93 (95% CI, 1.08-3.48,
=0.028) and 2.14 (95% CI, 1.58-2.90,
<0.0001), respectively, even after adjusting for age and comorbidity. For each 1 U decrease in MPR, the adjusted hazard ratios for death and MACE were 2.45 (95% CI, 1.42-4.24,
=0.001) and 1.74 (95% CI, 1.36-2.22,
<0.0001), respectively. In patients without regional perfusion defects on clinical read and no known macrovascular coronary artery disease (n=783), MPR remained independently associated with death and MACE, with stress MBF remaining associated with MACE only.
In patients with known or suspected coronary artery disease, reduced MBF and MPR measured automatically inline using artificial intelligence quantification of cardiovascular magnetic resonance perfusion mapping provides a strong, independent predictor of adverse cardiovascular outcomes.
Given the intersection between diabetes mellitus and cardiovascular disease (CVD), pharmacologic agents used to treat type 2 diabetes mellitus must show cardiovascular safety. Comorbid conditions, ...including heart failure and chronic kidney disease, are increasingly prevalent in patients with diabetes; therefore, they also play a large role in drug safety. Although biguanides, sulfonylurea, glitazones, and dipeptidyl peptidase 4 inhibitors have variable effects on cardiovascular events, sodium glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists have consistently shown safety and reduction in cardiovascular events in patients with established CVD. These medications are becoming essential tools for cardioprotection for patients with diabetes and CVD. They may also have roles in primary prevention and renal protection. This paper will review the cardiovascular impact, adverse effects, and possible mechanisms of action of pharmacologic agents used to treat patients with type 2 diabetes.
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•Historically, glycemic control was the primary focus in reducing cardiovascular risk in patients with diabetes mellitus.•Although historic agents effectively lower blood sugar, evidence for cardiovascular benefit was lacking.•Newer glucose-lowering medications target numerous novel pathways to reduce cardiovascular and renal events in patients with type 2 diabetes.•These medications should be considered in patients with diabetes and CVD and may play a role in primary prevention of cardiovascular and renal disease.
Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear.
This ...study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI.
In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(−) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI.
A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(−) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment.
Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment.
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•Recently, the REDUCE-IT study has reopened the debate about the CV benefit of omega-3 fatty acids.•n-3 PUFA supplementation significantly reduced cardiac mortality, major adverse ...cardiovascular events, and myocardial infarction.•These effects are seen only with dose >1 g/day and in patients at higher CV risk.•n-3 PUFA significantly reduced cardiac mortality, major adverse cardiovascular events, and myocardial infarction.
The recent publication of the REDUCE-IT study has reopened the debate about the efficacy of omega-3 fatty acids in reducing the risk of cardiovascular (CV) events. This meta-analysis aims at investigating the effect of omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA) administration on CV outcomes in published randomized clinical trials (RCTs), with a focus on the role of dose, type of n-3 PUFA, and different CV risk at baseline.
This meta-analysis was conducted according to the PRISMA reporting guidelines. PubMed, Cochrane and EMBASE were searched since inception to March 2020. Inclusion criteria were: (1) RCTs; (2) including subjects with previous CV events; (3) administration of n-3 PUFA ≥ 1 g/day dosage for ≥1 year; (4) effects on all-cause mortality, cardiac death, major adverse cardiovascular events (MACE), fatal/nonfatal myocardial infarction (MI), or fatal/nonfatal stroke reported. Odds ratios (ORs) with 95 % confident intervals (95 %CI) were estimated.
16 RCTs were included in the meta-analysis accounting for 81,073 participants. Supplementation of n-3 PUFA was associated with a significant risk reduction of cardiac mortality (OR 0.91 95 % CI, 0.85−0.98), MACE (OR 0.90 95 % CI, 0.82−0.99), and MI (OR 0.83 95 % CI, 0.71−0.98). In subgroup analyses, the risk reduction of cardiac mortality and MI was confirmed only in RCTs that enrolled patients in secondary prevention (-21 % and -31 %, respectively). Moreover, only the administration of more than 1 g per day of n-3 PUFA was effective in reducing the risk of cardiac death (-35 %), MACE (-24 %), and MI (-33 %). Finally, EPA + DHA supplementation was only associated with a significant risk reduction of cardiac death compared with EPA administered alone (-8 %). Conversely, the efficacy of EPA administered alone seemed to be greater in terms of risk reduction of MACE (-25 %) or MI (-30 %) than the combined EPA + DHA supplementation.
The pharmacological approach with n-3 PUFA significantly improves cardiovascular outcomes, with higher benefit achieved by patients in secondary CV prevention, using more than 1 g/day, and taking EPA administered alone.
Abstract
Aims
Clinical trials have demonstrated that a reduction in low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular (CV) events. This has, however, not yet been shown in a ...real-world setting. We aimed to investigate the association between LDL-C changes and statin intensity with prognosis after a myocardial infarction (MI).
Methods and results
Patients admitted with MI were followed for mortality and major CV events. Changes in LDL-C between the MI and a 6- to 10-week follow-up visit were analysed. The associations between quartiles of LDL-C change and statin intensity with outcomes were assessed using adjusted Cox regression analyses. A total of 40 607 patients were followed for a median of 3.78 years. The median change in LDL-C was a 1.20 mmol/L reduction. Patients with larger LDL-C reduction (1.85 mmol/L, 75th percentile) compared with a smaller reduction (0.36 mmol/L, 25th percentile) had lower hazard ratios (HR) for all outcomes (95% confidence interval): composite of CV mortality, MI, and ischaemic stroke 0.77 (0.70–0.84); all-cause mortality 0.71 (0.63–0.80); CV mortality 0.68 (0.57–0.81); MI 0.81 (0.73–0.91); ischaemic stroke 0.76 (0.62–0.93); heart failure hospitalization 0.73 (0.63–0.85), and coronary artery revascularization 0.86 (0.79–0.94). Patients with ≥50% LDL-C reduction using high-intensity statins at discharge had a lower incidence of all outcomes compared with those using a lower intensity statin.
Conclusions
Larger early LDL-C reduction and more intensive statin therapy after MI were associated with a reduced hazard of all CV outcomes and all-cause mortality. This supports clinical trial data suggesting that earlier lowering of LDL-C after an MI confers the greatest benefit.
Graphical Abstract
Potentiation of glucagon-like peptide-1 (GLP-1) action through selective GLP-1 receptor (GLP-1R) agonism or by prevention of enzymatic degradation by inhibition of dipeptidyl peptidase-4 (DPP-4) ...promotes glycemic reduction for the treatment of type 2 diabetes mellitus by glucose-dependent control of insulin and glucagon secretion. GLP-1R agonists also decelerate gastric emptying, reduce body weight by reduction of food intake and lower circulating lipoproteins, inflammation, and systolic blood pressure. Preclinical studies demonstrate that both GLP-1R agonists and DPP-4 inhibitors exhibit cardioprotective actions in animal models of myocardial ischemia and ventricular dysfunction through incompletely characterized mechanisms. The results of cardiovascular outcome trials in human subjects with type 2 diabetes mellitus and increased cardiovascular risk have demonstrated a cardiovascular benefit (significant reduction in time to first major adverse cardiovascular event) with the GLP-1R agonists liraglutide (LEADER trial Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Ourcome Results, -13%) and semaglutide (SUSTAIN-6 trial Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide, -24%). In contrast, cardiovascular outcome trials examining the safety of the shorter-acting GLP-1R agonist lixisenatide (ELIXA trial Evaluation of Lixisenatide in Acute Coronary Syndrom) and the DPP-4 inhibitors saxagliptin (SAVOR-TIMI 53 trial Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53), alogliptin (EXAMINE trial Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care in Patients With Type 2 Diabetes Mellitus and Acute Coronary Syndrome), and sitagliptin (TECOS Trial Evaluating Cardiovascular Outcomes With Sitagliptin) found that these agents neither increased nor decreased cardiovascular events. Here we review the cardiovascular actions of GLP-1R agonists and DPP-4 inhibitors, with a focus on the translation of mechanisms derived from preclinical studies to complementary findings in clinical studies. We highlight areas of uncertainty requiring more careful scrutiny in ongoing basic science and clinical studies. As newer more potent GLP-1R agonists and coagonists are being developed for the treatment of type 2 diabetes mellitus, obesity, and nonalcoholic steatohepatitis, the delineation of the potential mechanisms that underlie the cardiovascular benefit and safety of these agents have immediate relevance for the prevention and treatment of cardiovascular disease.
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