Cardiovascular disease (CVD) is a global health concern, causing significant morbidity and mortality. Both lifestyle and genetics influence the development of CVD. It is often diagnosed late, when ...the treatment options are limited. Early diagnosis of CVD with help of biomarkers is necessary to prevent adverse outcomes. SARS-CoV-2 infection can cause cardiovascular complications even in patients with no prior history of CVD. This review highlights cardiovascular biomarkers, including novel ones, and their applications as diagnostic and prognostic markers of cardiovascular complications related to SARS-CoV-2 infection. Patients with severe SARS-CoV-2 infection were shown to have elevated levels of cardiac biomarkers, namely N-terminal pro-brain natriuretic peptide (NT-pro-BNP), creatine kinase-myocardial band (CK-MB), and troponins, indicating acute myocardial damage. These biomarkers were also associated with higher mortality rates and therefore should be used throughout COVID-19 patient care to identify high-risk patients promptly to optimize their outcomes. Additionally, microRNAs (miRNAs) are also considered as potential biomarkers and predictors of cardiac and vascular damage in SARS-CoV-2 infection. Identifying molecular pathways contributing to cardiovascular manifestations in COVID-19 is essential for development of early biomarkers, identification of new therapeutic targets, and better prediction and management of cardiovascular outcomes.
Cardiovascular diseases are among the leading causes of morbidity and mortality, particularly in individuals with type 2 diabetes. There is a need for new biomarkers to improve the prediction of ...cardiovascular events and overall mortality. We investigated the association of selected atherosclerosis related biomarkers, specifically osteoprotegerin (OPG), 25-hydroxy-vitamin D (25(OH)D), C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), and asymmetric dimethylarginine (ADMA), with the occurrence of any cardiovascular event or all-cause mortality (primary outcome) during a 5.6-year follow-up of 190 patients with type 2 diabetes. Data were analyzed using logistic regression to adjust for baseline cardiovascular status and cardiovascular risk factors. The primary outcome occurred in 89 participants (46.8%) during the study. When analyzed individually, 25(OH)D, CRP, and LBP significantly predicted the primary outcome in multivariable models. However, in a model that included all biomarkers, only a decreased level of 25(OH)D remained a significant predictor of the primary outcome. Moreover, the level of 25(OH)D significantly predicted all-cause mortality: a reduction of 10 ng/mL was associated with a two-fold increase in all-cause mortality. Our study thus demonstrates that vitamin D deficiency was the strongest factor associated with the primary outcome and all-cause mortality after a 5.6-year follow-up in patients with type 2 diabetes at high cardiovascular risk.
Aims/hypothesis
The aim of this work was to investigate the mechanisms underlying the risk of type 2 diabetes associated with statin treatment in the population-based Metabolic Syndrome in Men ...(METSIM) cohort.
Methods
A total of 8,749 non-diabetic participants, aged 45–73 years, were followed up for 5.9 years. New diabetes was diagnosed in 625 men by means of an OGTT, HbA
1c
≥6.5% (48 mmol/mol) or glucose-lowering medication started during the follow-up. Insulin sensitivity and secretion were evaluated with OGTT-derived indices.
Results
Participants on statin treatment (
N
= 2,142) had a 46% increased risk of type 2 diabetes (adjusted HR 1.46 95% CI 1.22, 1.74). The risk was dose dependent for simvastatin and atorvastatin. Statin treatment significantly increased 2 h glucose (2hPG) and glucose AUC of an OGTT at follow-up, with a nominally significant increase in fasting plasma glucose (FPG). Insulin sensitivity was decreased by 24% and insulin secretion by 12% in individuals on statin treatment (at FPG and 2hPG <5.0 mmol/l) compared with individuals without statin treatment (
p
< 0.01). Decreases in insulin sensitivity and insulin secretion were dose dependent for simvastatin and atorvastatin.
Conclusions/interpretation
Statin treatment increased the risk of type 2 diabetes by 46%, attributable to decreases in insulin sensitivity and insulin secretion.
Statins are widely used in the treatment of hypercholesterolemia and are efficient in the prevention of cardiovascular disease. Molecular mechanisms explaining statin-induced impairment in insulin ...secretion remain largely unknown. In the current study, we show that simvastatin decreased glucose-stimulated insulin secretion in mouse pancreatic MIN6 β-cells by 59% and 79% (p<0.01) at glucose concentration of 5.5 mmol/l and 16.7 mmol/l, respectively, compared to control, whereas pravastatin did not impair insulin secretion. Simvastatin induced decrease in insulin secretion occurred through multiple targets. In addition to its established effects on ATP-sensitive potassium channels (p = 0.004) and voltage-gated calcium channels (p = 0.004), simvastatin suppressed insulin secretion stimulated by muscarinic M3 or GPR40 receptor agonists (Tak875 by 33%, p = 0.002; GW9508 by 77%, p = 0.01) at glucose level of 5.5 mmol/l, and inhibited calcium release from the endoplasmic reticulum. Impaired insulin secretion caused by simvastatin treatment were efficiently restored by GPR119 or GLP-1 receptor stimulation and by direct activation of cAMP-dependent signaling pathways with forskolin. The effects of simvastatin treatment on insulin secretion were not affected by the presence of hyperglycemia. Our observation of the opposite effects of simvastatin and pravastatin on glucose-stimulated insulin secretion is in agreement with previous reports showing that simvastatin, but not pravastatin, was associated with increased risk of incident diabetes.
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