Despite improvements in interventional and pharmacological therapy of atherosclerotic disease, it is still the leading cause of death in the developed world. Hence, there is a need for further development of effective therapeutic approaches. This requires better understanding of the molecular mechanisms and pathophysiology of the disease. Atherosclerosis has long been identified as having an inflammatory component contributing to its pathogenesis, whereas the available therapy primarily targets hyperlipidemia and prevention of thrombosis. Notwithstanding a pleotropic anti-inflammatory effect to some therapies, such as acetyl salicylic acid and the statins, none of the currently approved medicines for management of either stable or complicated atherosclerosis has inflammation as a primary target. Monocytes, as representatives of the innate immune system, play a major role in the initiation, propagation, and progression of atherosclerosis from a stable to an unstable state. Experimental data support a role of monocytes in acute coronary syndromes and in outcome post-infarction; however, limited research has been done in humans. Analysis of expression of various cell surface receptors allows characterization of the different monocyte subsets phenotypically, whereas downstream assessment of inflammatory pathways provides an insight into their activity. In this review we discuss the functional role of monocytes and their different subpopulations in atherosclerosis, acute coronary syndromes, cardiac healing, and recovery with an aim of critical evaluation of potential future therapeutic targets in atherosclerosis and its complications. We will also discuss technical difficulties of delineating different monocyte subpopulations, understanding their differentiation potential and function.

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Monocyte subset Mon2 and monocyte phagocytic activity undergo significant diurnal variation. A single bout of exercise causes a temporal increase in monocytes and a reduction in MPAs. Monocyte subset counts should be analysed within 2 h of blood sampling, whereas measurement of MPAs and monocyte CD14 and CD16 expression should be performed within 1 h.

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Aims There are limited data on the role of human monocyte subsets in ST‐elevation myocardial infarction (STEMI). The study aimed to establish the relationship between monocyte subsets, their phagocytic and nuclear factor κB (NFκB) activity and outcomes in STEMI. Methods Monocyte subsets and their phagocytic activity and intracellular levels of inhibitory κB kinase β (IKKβ, marker of NFκB activity) were measured by flow cytometry in 245 patients with STEMI, median follow‐up of 46 months. Results Mon2 (CD14++CD16+CCR2+) counts were independently predictive of major adverse cardiovascular events (MACE) [4th quartile HR 3.42 (95% CI 1.43–8.16), P = 0.006 and 3rd quartile HR 2.88 (95% CI 1.19–7.00), P = 0.02 vs. 1st quartile]. Mon2 subset was the only subset associated with higher occurrence of heart failure (4th quartile vs. 1st quartile, sevenfold, P = 0.001 on univariate analysis; fivefold, P = 0.04 on multivariable analysis). On receiver operating characteristic, analysis including of Mon2 improved prognostic value of troponin T and creatine kinase for MACE and heart failure (HF). Higher intracellular Mon2 IKKβ levels were associated with 10‐fold lower occurrence of HF on multivariable analysis (4th vs. 1st quartiles, P = 0.03). Abnormal Mon1 and Mon2 phagocytic capacities were related to HF development, but the association was dependent on the infarct size and other prognosticators. High Mon2 levels were associated with lower ejection fraction after STEMI onset (P = 0.001) and at 6‐month follow‐up (P < 0.001). Conclusions Abnormal Mon2 characteristics have a unique association with poor outcome in patients with STEMI. The relation of Mon2 with occurrence of HF is strongly and independently related to their functional status, which may have potential therapeutic implications.

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Objective: This study sought to investigate the effect of body mass index on outcomes in patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation.Methods: A total of 12,381 patients undergoing transfemoral transcatheter aortic valve implantation were divided into body mass index categories: underweight (<18.5 kg/m 2 ), normal weight (18.5-24.9 kg/m 2 ), overweight (25.0-29.9 kg/m 2 ), and obesity (>30 kg/m 2 ). Primary endpoints were differences in 30-day and 1-year allcause mortality. Secondary endpoints included all other clinical endpoints such as stroke. Univariate and multivariate odds ratios were calculated using logistic and cox regression analyses.Results: Two percent (n ¼ 205) of patients were underweight, 29% (n ¼ 3564) were normal weight, 44% (n ¼ 5460) were overweight, and 25% (n ¼ 3152) were obese. Thirty-day mortality was lower in overweight (5.3%, odds ratio, 0.73; 95% confidence interval, 0.61-0.88; P ¼ .001) and obese patients (5.2%, odds ratio, 0.74; 95% confidence interval, 0.60-0.92; P ¼ .006), but higher in underweight (9.8%, odds ratio, 1.51; 95% confidence interval, 0.92-2.47; P ¼ .010) as compared to normal weight patients (6.9%). After multivariate adjustment, 30-day mortality was not significantly different across body mass index categories. However, 1-year mortality was higher in underweight patients (hazard ratio, 1.52; 95% confidence interval, 1.10-2.09; P ¼ .011). Stroke rates were comparable between body mass index groups.Conclusions: For overweight and obese patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation, there was no 30-day difference in mortality compared with patients with normal weight. However, underweight patients showed higher rates of 1-year mortality after transcatheter aortic valve implantation.