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High levels of lipoprotein(a) [Lp(a)] are considered causal risk factor of cardiovascular disease (CVD), including aortic stenosis. The 2019 ESC/EAC guidelines for the management of dyslipidaemias recommend to measure Lp(a) at least once in each adult person’s lifetime to identify those with inherited Lp(a) levels > 180 mg/dL (> 430 nmol/L) who may have a cardiovascular risk similar to heterozygous familial hypercholesterolaemia or in selected patients with a family history of premature CVD and for reclassification in people who are borderline between moderate- and high-risk. Some lipid-lowering agents not specific for Lp(a) have shown to reduce Lp(a) levels (niacin, PCSK9 inhibitors and CETP inhibitors). Prespecified analyses from the FOURIER trial have shown that participants who had reduction in Lp(a) levels with PCSK9 levels had a decreased risk of cardiovascular events. To lower Lp(a), two antisense oligonucleotides are under development targeting apolipoprotein B and apolipoprotein (a). Mipomersen is an oligonucleotide that targets apolipoprotein B, with a potential benefit in reducing Lp(a) by 20–50%. AKCEA-APO(a)- L RX is another antisense oligonucleotide targeting Lp(a) and reducing Lp(a) by 50–80%. A Phase III study with AKCEA-APO(a)- L RX will start in order to evaluate the effect on cardiovascular outcomes.

The cardiovascular (CV) benefit and safety of treating low testosterone conditions is a matter of debate. Although testosterone deficiency has been linked to a rise in major adverse CV events, most of the studies on testosterone replacement therapy were not designed to assess CV risk and thus excluded men with advanced heart failure or recent history of myocardial infarction or stroke. Besides considering observational, interventional and prospective studies, this review article evaluates the impact of testosterone on atherosclerosis process, including lipoprotein functionality, progression of carotid intima media thickness, inflammation, coagulation and thromboembolism, quantification of plaque volume and vascular calcification. Until adequately powered studies evaluating testosterone effects in hypogonadal men at increased CV risk are available (TRAVERSE trial), clinicians should ponder the use of testosterone in men with atherosclerotic cardiovascular disease and discuss benefit and harms with the patients.

We provide an update regarding the differences between men and women in short-term postoperative mortality after coronary artery bypass grafting (CABG) and highlight the differences in postoperative risk of stroke, myocardial infarction, and new onset atrial fibrillation. We included 23 studies, with a total of 3,971,267 patients (70.7% men, 29.3% women), and provided results for groups of unbalanced studies and propensity matched studies. For short-term mortality, the pooled odds ratio (OR) from unbalanced studies was 1.71 (with 95% CI 1.69–1.74, I 2  = 0%, p  = 0.7), and from propensity matched studies was 1.32 (95% CI 1.14–1.52, I 2  = 76%, p  < 0.01). For postoperative stroke, the pooled effects were OR = 1.50 (95% CI 1.35–1.66, I 2  = 83%, p  < 0.01) and OR = 1.31 (95% CI 1.02–1.67, I 2  = 81%, p  < 0.01). For myocardial infarction, the pooled effects were OR = 1.09 (95% CI = 0.78–1.53, I 2  = 70%, p  < 0.01) and OR = 1.03 (95% CI = 0.86–1.24, I 2  = 43%, p  = 0.18). For postoperative atrial fibrillation, the pooled effect from unbalanced studies was OR = 0.89 (95% CI = 0.82–0.96, I 2  = 34%, p  = 0.18). The short-term mortality risk after CABG is higher in women, compared to men. Women are at higher risk of postoperative stroke. There is no significant difference in the likelihood of postoperative myocardial infarction in women compared to men. Men are at higher risk of postoperative atrial fibrillation after CABG.

Osteoporosis is a major public health burden that is expected to further increase as the global population ages. In the last twenty years, advanced glycation end products (AGEs) have been shown to be critical mediators both in the pathogenesis and development of osteoporosis and other chronic degenerative diseases related to aging. The accumulation of AGEs within the bone induces the formation of covalent cross-links with collagen and other bone proteins which affects the mechanical properties of tissue and disturbs bone remodelling and deterioration, underlying osteoporosis. On the other hand, the gradual deterioration of the immune system during aging (defined as immunosenescence) is also characterized by the generation of a high level of oxidants and AGEs. The synthesis and accumulation of AGEs (both localized within the bone or in the systemic circulation) might trigger a vicious circle (in which inflammation and aging merged in the word “Inflammaging”) which can establish and sustain the development of osteoporosis. This narrative review will update the molecular mechanisms/pathways by which AGEs induce the functional and structural bone impairment typical of osteoporosis.

In this clinical trial, rosuvastatin was compared with placebo in elderly patients with systolic, ischemic heart failure. Although rosuvastatin significantly lowered levels of both low-density lipoprotein cholesterol and high-sensitivity C-reactive protein, it did not significantly reduce cardiovascular outcomes. However, it did reduce the number of hospitalizations. On the basis of these data, the role of statin therapy in heart failure appears to be limited. Although rosuvastatin significantly lowered levels of both low-density lipoprotein cholesterol and high-sensitivity C-reactive protein, it did not significantly reduce cardiovascular outcomes. Although a high proportion of patients with heart failure caused by left ventricular systolic dysfunction have coronary artery disease, reported rates of myocardial infarction have been low in previous clinical trials. 1 – 4 Therefore, the potential value of statins has been questioned because their benefit is largely due to the prevention of myocardial infarction. In addition, in this population of patients, low levels of total cholesterol are common and are associated with worse outcomes. 1 – 6 Lipoproteins may remove endotoxins that enter the circulation through the intestinal wall, which may be edematous and leaky in patients with heart failure. 7 Statins could also . . .

Aims: The HEYMANS study observed patients receiving evolocumab as part of routine clinical hyperlipidemia management. It was designed to capture data on clinical parameters relevant to health authorities and physicians. Methods: This was a European multi-country observational cohort serial chart review study; data on the Swiss cohort are reported here. Patients were prescribed evolocumab as per the Swiss reimbursement criteria in force at the time and were invited chronologically. The study consisted of a 6-month period prior to initiation of evolocumab, a 12-month core observation period (entered by 75 patients, completed by 74 patients), and an 18-month extended observation period (entered by 40 patients, completed by 34 patients). The primary objective was to describe the clinical characteristics of patients receiving evolocumab. Secondary objectives included to describe lipid levels, evolocumab use, and patterns of use of other lipid-lowering therapies (LLT, that is, statins and/or ezetimibe) over time. The study was conducted in the Swiss cohort between May 2017 and June 2021. Results: Patients who received evolocumab in Swiss routine practice mostly were in secondary prevention (93%) and had a history of statin intolerance (85%) with 53% receiving no background LLT. One-third had familial hypercholesterolemia. Patients initiated evolocumab at a median low-density lipoprotein cholesterol (LDL-C) of 3.6 mmol/L, which decreased by 54% within 3 months to 1.6 mmol/L and was stable thereafter. Overall, 61% achieved the LDL-C goal of <1.4 mmol/L with more patients attaining this goal when they received evolocumab with a statin and/or ezetimibe (84%) compared to 41% when receiving evolocumab alone. An LDL-C reduction of ⩾50% was achieved by 85% of patients. Persistence with evolocumab at 12 months was 85%. Conclusion: In Swiss clinical practice, evolocumab was mainly prescribed to patients with very high cardiovascular risk, who had very high LDL-C levels. Most patients continued to use evolocumab throughout the study period. In these patients, LDL-C was reduced by >50% within 3 months and LDL-C reductions were maintained over time. Guideline-recommended LDL-C goals for this very high-risk cohort were more frequently attained in patients receiving a combination of statin and/or ezetimibe and evolocumab. Trial registration: ClinicalTrials.gov Identifier: NCT02770131.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, or statins, are effective lipid-lowering agents, extensively used in medical practice 1 , 2 , 3 . Statins have never been shown to be involved in the immune response, although a report has indicated a better outcome of cardiac transplantation in patients under Pravastatin therapy 4 . Major histocompatibility complex class II (MHC-II) molecules are directly involved in the activation of T lymphocytes and in the control of the immune response. Whereas only a limited number of specialized cell types express MHC-II constitutively, numerous other cells become MHC-II positive upon induction by interferon γ (IFN-γ) 5 . This complex regulation is under the control of the transactivator CIITA (refs 6 , 7 ). Here we show that statins act as direct inhibitors of induction of MHC-II expression by IFN-γ and thus as repressors of MHC-II-mediated T-cell activation. This effect of statins is due to inhibition of the inducible promoter IV of the transactivator CIITA and is observed in several cell types, including primary human endothelial cells (ECs) and monocyte-macrophages (Mφ). It is of note that this inhibition is specific for inducible MHC-II expression and does not concern constitutive expression of CIITA and MHC-II. In repressing induction of MHC-II, and subsequent T-lymphocyte activation, statins therefore provide a new type of immunomodulation. This unexpected effect provides a scientific rationale for using statins as immunosuppressors, not only in organ transplantation but in numerous other pathologies as well.

Anti-inflammatory activities of statins in atherosclerosis have been well documented by both basic research and clinical studies. Statins have been introduced in the 1980s as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors to block cholesterol synthesis and lower cholesterol serum levels. In the last three decades, statins have been shown to possess several anti-inflammatory and antioxidant activities resulting in the beneficial reduction of atherosclerotic processes and cardiovascular risk in both humans and animal models. Inflammatory intracellular pathways involving kinase phosphorylation and protein prenylation are modulated by statins. The same intracellular mechanisms might also cause statin-induced myotoxicity. In the present review, we will update evidence on statin-mediated regulation of inflammatory pathways in atherogenesis.

To examine the prognosis of patients with cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome compared to patients without prior multimorbidity. This multicenter prospective cohort study in Switzerland included 5,635 patients hospitalized with acute coronary syndrome between 2009 and 2014, with a one-year follow-up period. We defined cardiovascular and non-cardiovascular multimorbidity as having at least two prior comorbidities before the index hospitalization. Multivariable adjusted Cox proportional models were built to assess the one-year risk of recurrent cardiovascular events, defined as cardiovascular mortality and non-fatal myocardial infarction or stroke. The final model was adjusted for age, gender, body mass index, tobacco consumption, education, and family history of cardiovascular disease, prescription of high-dose statinsat discharge and use of cardiac rehabilitation after discharge. Overall, 3,664 patients (65%) had no multimorbidity, 1,839 (33%) had cardiovascular multimorbidity, 62 (1%) had non-cardiovascular multimorbidity, and 70 (1%) had both cardiovascular and non-cardiovascular multimorbidity. The multivariate risk of recurrent cardiovascular events was increased among patients with cardiovascular multimorbidity (hazard ratio (HR) 2.05, 95% CI: 1.54-2.73, p<0.001) and patients with non-cardiovascular multimorbidity (HR 2.57, 95% CI: 1.04-6.35, p = 0.04) compared to patients without multimorbidity. Patients with cardiovascular and non-cardiovascular multimorbidity had the highest risk of recurrence with a HR of 5.19, 95% CI: 2.79-9.64, p<0.001, compared to patients without multimorbidity. Multimorbidity increased by two-fold the risk of cardiovascular events over the year after an acute coronary syndrome. The magnitude of this increased risk was similar for patients with cardiovascular or non-cardiovascular multimorbidity.

Studies showing that the management of dyslipidemia is suboptimal are hampered by their cross-sectional design or short follow-up. Using recent data from a population-based cohort with a 10-year follow-up, we assessed the use of statins, including their intensity. We used data from the CoLaus|PsyColaus study, involving 4,655 participants at baseline (2003 to 2006) and 3,587 at 10-year follow-up (2014 to 2017). We assessed the cardiovascular risk of participants according to established guidelines from the European Society of Cardiology (ESC) and from the American Heart Association/American College of Cardiology and estimated 10-year cardiovascular risk using corresponding risk scores, Systemic Coronary Risk Evaluation risk prediction model and Pooled Cohort Equations. We first determined eligibility for statins and adherence to recommendations at 2 time periods. Additionally, we assessed the prevalence of statin users from 2014 to 2017 in persons without atherosclerotic cardiovascular disease at baseline and who developed it during the follow-up (secondary prevention). A total of 219 participants developed a first atherosclerotic cardiovascular disease during follow-up. Statin use in eligible subjects was 25.9% and 24.0% from 2003 to 2006 and 35.9% and 26.3% from 2014 to 2017, according to ESC and American Heart Association/American College of Cardiology guidelines, respectively. Per ESC guidelines, only 28.2% of treated persons achieved low-density lipoproteins cholesterol target levels from 2014 to 2017 (15.8% from 2003 to 2006), and women less frequently attained goals. Only 18% of subjects used high-intensity statins from 2014 to 2017, with women less often receiving them (14% vs 22%). In secondary prevention, only 74% of eligible subjects were using statins. In conclusion, based on contemporaneous data, management of dyslipidemia is suboptimal, including in secondary prevention, especially in women who are less frequently treated and, if treated, less frequently receive high-intensity treatment.