Executive summary of the Hellenic Atherosclerosis Society guidelines for the diagnosis and treatment of dyslipidemias - 2023.

Atherosclerotic cardiovascular disease (ASCVD) remains the main cause of death worldwide, and thus its prevention, early diagnosis and treatment is of paramount importance. Dyslipidemia represents a major ASCVD risk factor that should be adequately managed at different clinical settings. 2023 guidelines of the Hellenic Atherosclerosis Society focus on the assessment of ASCVD risk, laboratory evaluation of dyslipidemias, new and emerging lipid-lowering drugs, as well as diagnosis and treatment of lipid disorders in women, the elderly and in patients with familial hypercholesterolemia, acute coronary syndromes, heart failure, stroke, chronic kidney disease, diabetes, autoimmune diseases, and non-alcoholic fatty liver disease. Statin intolerance is also discussed.

Daylight saving time and myocardial infarction: should we be worried? A review of the evidence.

Transitions into and out of Daylight Saving Time (DST) may disrupt circadian rhythms and lead to sleep disturbance and deprivation. A first report observed an association between DST and acute myocardial infarction (AMI), especially after the spring shift and in women. We tried to identify and evaluate the possible association between DST and AMI, using the MEDLINE, EMBASE and Google Scholar electronic database (years 2009-2016), with regards to the searching terms 'daylight saving time', 'daylight saving time' plus 'gender', and 'daylight saving time' plus 'acute myocardial infarction'. In total, 72, 10, and 6 studies were found, respectively. Overall, 6 studies, including a total of 87,994 cases, resulted to satisfy the searching request, and were included in the present analysis. All studies confirmed a higher occurrence of AMI in the spring shift, ranging from 4 to 29%, whereas only 1 study showed a higher occurrence of AMI in the autumn shift. By the way, in 5 studies providing separate analysis, the results by sex were not univocal. In fact, as for the spring shift, 2 studies did not show differences between men and women, 2 reported a higher frequency in men, and 1 in women. Regarding the autumn shift, only 1 study reported a higher occurrence of AMI in women. These results support the presence of an association between DST and a modest increase of AMI occurrence, especially for the spring shift, and with no definite gender specific differences.

Emerging Vascular Risk Factors in Women: Any Differences from Men?

Gender differences have been reported for traditional vascular risk factors such as smoking, obesity, diabetes, hypertension, dyslipidemia, age and family history of premature coronary heart disease. The prevalence, severity, associations and response to treatment of several emerging cardiovascular disease (CVD) risk factors may also differ between men and women. Such CVD risk factors include certain inflammatory and hemostatic markers, endothelial dysfunction, homocysteine, lipid disorders, microalbuminuria/proteinuria, coronary artery calcium score, arterial stiffness, periodontitis, inflammatory bowel syndrome, obstructive sleep apnea, impaired glucose metabolism, metabolic syndrome and non-alcoholic fatty liver disease. Further larger prospective studies are needed to establish these relationships. Hormone replacement therapy may also affect vascular risk. These data should be taken into consideration when assessing and treating CVD risk in women.

Chronic Venous Disease and Comorbidities.

We report the relations between comorbidities and chronic venous disease. In this cross-sectional study, information was gathered from 1679 Serbian patients. The majority (65.0%) of patients were women. Mild forms of chronic venous disease (clinical, etiologic, anatomic and pathophysiologic [CEAP] classification; C0s-C1) were more frequent in women (11.6%), while severe forms (CEAP C4-C6) were more commonly encountered in men (42.1%). The most frequent comorbidity was emphysema/chronic obstructive pulmonary disease in both groups (74.3% in males and 70.6% in females). For females, diabetes mellitus (P < .005), arterial hypertension (P < .000), and skeletal/joint diseases (P < .042) were more commonly found in the C4 to C6 category. Both males and females, with severe form of chronic venous disease, may benefit from additional screening for comorbidities. Further studies are needed to clarify the nature of association among comorbidities and chronic venous disease.

High-density lipoprotein, vascular risk, cancer and infection: a case of quantity and quality?

Low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with increased cardiovascular (CV) risk. These beneficial effects of HDL can be, at least partly, attributed to its anti-inflammatory, antithrombotic, antioxidant and endothelial-protective properties. However, the results of some clinical trials aiming at raising HDL-C levels are conflicting in terms of CV protection suggesting that alterations in HDL quality (and not only quantity) are involved in the atherosclerotic process. In this context, inflammation, oxidation, infection, hyperglycemia and activated platelets may modify HDL components, thus transforming HDL to a dysfunctional molecule with pro-atherogenic properties. Furthermore, some recent trials with HDL-raising drugs, such as niacin and torcetrapib, reported a lack of benefit in terms of vascular risk as well as adverse events including cancer and infections. In this narrative review, the findings of recent HDL clinical studies in relation to CV events as well as the associations of HDL with cancer and infections are discussed. The possible pathogenic mechanisms of these associations are also considered. The clinical implications of HDL function in treating patients at high CV risk remains to be established in future trials.

The indicator test Neuropad in the assessment of small and overall nerve fibre dysfunction in patients with type 2 diabetes: a large multicentre study.

We examined the diagnostic utility of the indicator test Neuropad in the assessment of overall and small fibre dysfunction in 1,010 patients with type 2 diabetes mellitus (T2DM) (608 men, mean age 63.9 ± 10.3 years) from 5 diabetes clinics. Sudomotor function was diagnosed by the Neuropad® test. Overall and small nerve fibre dysfunction was diagnosed through clinical examination and symptoms. Patients were divided into Groups A (441 patients with sudomotor dysfunction) and B (569 patients without sudomotor dysfunction). The former were older (p<0.05) and had longer T2DM duration (p<0.05) than the latter. For overall nerve fibre dysfunction, abnormal Neuropad defined as patchy/blue had 94.9% sensitivity, 70.2% specificity and 98.1% negative predictive value (NPV), while for small fibre dysfunction the corresponding values were 85.6%, 71.2% and 93.3%. For overall nerve fibre dysfunction, abnormal Neuropad defined as blue had 64% sensitivity, 96% specificity and 91% NPV, while for small fibre dysfunction the corresponding values were 52%, 96% and 85%. The odds ratios (ORs) of Neuropad patchy/blue for overall and for small fibre dysfunction were 43.7 and 14.7, respectively. The ORs of Neuropad blue for overall and for small fibre dysfunction were 45.7 and 24.9, respectively. In conclusion, Neuropad patchy/blue response exhibited better diagnostic performance both for overall and small nerve fibre dysfunction. Its very high NPV renders it an excellent screening tool primarily to exclude neuropathy in T2DM.

Smoking and vascular risk: are all forms of smoking harmful to all types of vascular disease?

Smoking, both active and passive, is an established vascular risk factor. The present narrative review considers the effects of different forms of smoking (i.e. cannabis, cigar, pipe, smokeless tobacco and cigarette) on cardiovascular risk. Furthermore, the impact of smoking on several vascular risk factors [e.g. hypertension, diabetes mellitus (DM), dyslipidaemia and haemostasis] and on vascular diseases such as coronary heart disease (CHD), peripheral arterial disease (PAD), abdominal aortic aneurysms (AAA) and carotid arterial disease, is discussed. The adverse effects of all forms of smoking and the interactions between smoking and established vascular risk factors highlight the importance of smoking cessation in high-risk patients in terms of both primary and secondary vascular disease prevention. Healthcare providers should discourage people (especially the young) from becoming smokers, strongly encourage all vascular patients to stop smoking and support those who decide to quit by pharmaceutical and psychological interventions. In high-risk populations such as patients with CHD, DM and/or PAD, smoking cessation should always be a part of a multifactorial treatment to reduce vascular risk.

Diabetes, bilirubin and amputations: is there a link?

A study by Chan et al in this issue of Diabetologia (DOI: 10.1007/s00125-012-2818-4 ) reports that low plasma bilirubin levels are associated with an increased risk of amputation in patients with type 2 diabetes mellitus participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. These findings raise the interesting and clinically relevant hypothesis that bilirubin protects against risk of amputation in patients with type 2 diabetes. This commentary considers some of the limitations associated with research aiming to define any link between circulating bilirubin levels and vascular disease. Numerous confounding factors (several of which may be present in patients with type 2 diabetes) may explain why the literature regarding this potentially protective role of bilirubin remains controversial.

Increased serum levels of uric acid are associated with sudomotor dysfunction in subjects with type 2 diabetes mellitus.

The aim of this paper was to assess serum uric acid (SUA) levels in patients with type 2 diabetes mellitus (T2DM) with or without sudomotor dysfunction (evaluated by the Neuropad test). We included 36 T2DM patients with sudomotor dysfunction (group A: mean age 63.1 ± 2.6 years) and 40 age-, gender-, renal function- and T2DM duration-matched patients without sudomotor dysfunction (group B: mean age 62.1 ± 3.1 years). SUA was significantly higher in group A (P < 0.001). There was a significant correlation between SUA and Neuropad time to colour change in both groups (group A: r(s) = 0.819, P < 0.001; group B: r(s) = 0.774, P < 0.001). There was also a significant positive correlation between SUA and CRP in both groups (group A: r(s) = 0.947, P < 0.001; group B: r(s) = 0.848, P < 0.001). In conclusion, SUA levels were higher in T2DM patients with sudomotor dysfunction than those without this complication. The potential role of SUA in sudomotor dysfunction merits further study.

Peripheral neuropathy is associated with increased serum levels of uric acid in type 2 diabetes mellitus.

We assessed serum uric acid (SUA) levels in patients with type 2 diabetes mellitus (T2DM) with or without peripheral neuropathy (diagnosed by the Neuropathy Disability score [NDS]). We enrolled 64 patients with T2DM with peripheral neuropathy (group A: 31 men, mean age 63.0 ± 2.8 years) and 66 age-, gender-, renal function- and T2DM duration-matched patients without neuropathy (group B: 32 men, mean age 62.4 ± 3.1 years). Serum uric acid was significantly higher in group A (P < .001). There was a significant correlation between SUA and NDS in both groups (group A: r(s) = .93, P < .001; group B: r( s) = .95, P < .001). C-reactive protein (CRP) was also significantly higher in group A (P < .001) and correlated significantly with SUA in both groups (group A: r(s) = .93, P < .001; group B: r(s) = .87, P < .001). Serum uric acid is increased in patients with T2DM with neuropathy versus those without. Whether SUA is involved in the pathogenesis of T2DM peripheral neuropathy remains to be established.

Implementation of strategy for the management of overt dyslipidemia: the IMPROVE-dyslipidemia study.

BACKGROUND: To assess the efficacy of a strategy aimed at improving vascular risk management in patients with dyslipidemia with or without cardiovascular disease (CVD). METHODS: This is a pilot implementation enhancement program that was evaluated in 1127 patients with dyslipidemia. There was a baseline visit, followed by a concerted effort from previously trained physicians to improve adherence to lifestyle advice and optimize drug treatment for all vascular risk factors. After 6 months the patients were re-evaluated. The PROspective-Cardiovascular-Munster (PROCAM) and Framingham trials risk engines were used to estimate CVD risk in primary prevention patients (n=609). RESULTS: This strategy induced a better compliance to lifestyle measures and use of evidence-based medication, focusing on statins. This resulted in a 45% (Framingham) to 63% (PROCAM) reduction in estimated CVD risk in primary prevention (both p<0.0001). There was also a substantial increase in the proportion of secondary prevention patients (n=518) achieving CVD risk factor targets (from 29% at baseline to 76% at 6 months, p<0.0001). CONCLUSIONS: This is the first study to increase the adherence to multiple interventions in patients with dyslipidemia, and other CVD risk factors, in both primary care and teaching hospital settings. Simple measures, such as educating physicians and patients, distributing printed guidelines and brochures, and completing a 1-page form, motivated physicians and patients to achieve multiple CVD risk factor goals.