Fotios Barkas

Diabetes mellitus and electrolyte disorders

Diabetic patients frequently develop a constellation of electrolyte disorders. These disturbances are particularly common in decompensated diabetics, especially in the context of diabetic ketoacidosis or nonketotic hyperglycemic hyperosmolar syndrome. These patients are markedly potassium-, magnesium- and phosphate-depleted. Diabetes mellitus (DM) is linked to both hypo- and hyper-natremia reflecting the coexistence of hyperglycemia-related mechanisms, which tend to change serum sodium to opposite directions. The most important causal factor of chronic hyperkalemia in diabetic individuals is the syndrome of hyporeninemic hypoaldosteronism. Impaired renal function, potassium-sparing drugs, hypertonicity and insulin deficiency are also involved in the development of hyperkalemia. This article provides an overview of the electrolyte disturbances occurring in DM and describes the underlying mechanisms. This insight should pave the way for pathophysiology-directed therapy, thus contributing to the avoidance of the several deleterious effects associated with electrolyte disorders and their treatment.

Lipid Target Achievement Among Patients With Very High and High Cardiovascular Risk in a Lipid Clinic

This was a retrospective study that assessed achievement of lipid-lowering treatment targets in the setting of a University Hospital Lipid Clinic. Low-density lipoprotein cholesterol (LDL-C) goal attainment according to National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines was recorded in 1000 consecutive adult patients followed for ≥3 years (mean 8 years). The LDL-C targets according to the NCEP ATP III were attained by 66% and 86% of patients with “very high” (n = 477) and “high” (n = 408) cardiovascular risk, respectively. Fewer patients were within LDL-C goals according to the ESC/EAS guidelines: 25% and 42%. Overall, 92% of the patients were on statins: 67% were on statin monotherapy, while 33% were on combinations with ezetimibe (25%), ω-3 fatty acids (5%), fibrates (4%), or colesevelam (2%). Even in a specialist lipid clinic, a large proportion of patients are not at goal according to the recent ESC/EAS guidelines.

Statins decrease the risk of stroke in individuals with heterozygous familial hypercholesterolemia: A systematic review and meta-analysis

BACKGROUND Familial hypercholesterolemia (FH) is undoubtedly associated with premature coronary heart disease, but it is debatable whether FH increases the risk for stroke. OBJECTIVE To meta-analyze available evidence regarding the incidence of stroke in individuals with heterozygous (He) FH. METHODS We conducted a systematic review and a meta-analysis of epidemiological studies, including English-language publications until June 2015; four observational studies, with 3374 participants with HeFH, were included in the analysis. Cerebrovascular disease comprised of ischemic stroke or transient ischemic attack. Since studies did not include any control subjects, the corresponding general population of the same reference area and period of time for each HeFH study served as control group. Analyses were performed according to the period of time during which the studies were conducted: prestatin and statin era (before and after 1987 when lovastatin was launched). RESULTS In the prestatin era, individuals with HeFH exhibited a higher risk for stroke compared with the general population [odds ratio (OR) = 7.658, 95% confidence interval (CI): 6.059-9.678, p < 0.01]. In contrast, FH subjects had a lower odds for stroke following the generalization of statin therapy (OR = 0.251, 95% CI: 0.176-0.358, p < 0.01). CONCLUSIONS Taking into account the small number of studies and methodological issues, HeFH was associated with a higher risk of cerebrovascular disease compared with the general population in the prestatin era, which was significantly reduced after the introduction of statin therapy.

How effective are the ESC/EAS and 2013 ACC/AHA guidelines in treating dyslipidemia? Lessons from a lipid clinic

Abstract Objective: There is a paucity of data regarding the attainment of lipid-lowering treatment goals according to the recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines. The aim of the present study was to assess how applicable these 2013 recommendations are in the setting of an Outpatient University Hospital Lipid Clinic. Methods: This was a retrospective (from 1999 to 2013) observational study including 1000 consecutive adults treated for hyperlipidemia and followed up for ≥3 years. Comparisons for the applicability of current European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) and recent ACC/AHA guidelines were performed. Results: Achievement rates of low density lipoprotein cholesterol (LDL-C) targets set by ESC/EAS were 21%, 44% and 62% among patients at very high, high and moderate cardiovascular risk, respectively, receiving statin monotherapy. Among individuals on high-intensity statins only 47% achieved the anticipated ≥50% LDL-C reduction, i.e. the ACC/AHA target. The corresponding rate was significantly greater among those on statin + ezetimibe (76%, p < 0.05). Likewise, higher rates of LDL-C target attainment according to ESC/EAS guidelines were observed in patients on statin + ezetimibe compared with statin monotherapy (37, 50 and 71% for the three risk groups, p < 0.05 for the very high risk group). Conclusion: The application of the ACC/AHA guidelines may be associated with undertreatment of high risk patients due to suboptimal LDL-C response to high-intensity statins in clinical practice. Adding ezetimibe substantially increases the rate of the ESC/EAS LDL-C target achievement together with the rate of LDL-C lowering response suggested by the ACC/AHA.

Statin therapy with or without ezetimibe and the progression to diabetes

OBJECTIVE To assess the risk of progression from normoglycemia or prediabetes to overt diabetes among individuals treated with statins alone or in combination with ezetimibe. METHODS This was a retrospective study conducted in Greece including 877 subjects treated for dyslipidemia. We included individuals without overt diabetes at baseline and divided them in 2 subgroups according to their baseline fasting glucose: <100 (normal glucose) and 100 to 125 mg/dL (prediabetes). High and moderate-intensity statin therapy was defined according to the expected low-density lipoprotein cholesterol reduction (≥50% and 30 to <50%, respectively). We identified the predictors of incident diabetes and assessed the risk of new-onset diabetes among subgroups on various intensity statin or no statin treatment at all. Similar analyses were performed across different potency of statin monotherapy or combination of statin plus ezetimibe treatment. RESULTS A total of 877 subjects were eligible and followed-up for a median of 7 years. There were no differences between statins regarding diabetes development. However, a higher risk of incident diabetes was observed in prediabetic individuals receiving high-intensity statin therapy compared with those on moderate intensity (adjusted odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.06-4.24, P < .05) and those not taking a statin (adjusted OR = 4.90; 95% CI = 1.16-20.66, P < .05). The addition of ezetimibe to statin treatment did not increase the risk of incident diabetes in prediabetic individuals (adjusted OR = 0.89; 95% CI = 0.36-2.22, P > .05). Baseline fasting glucose, presence of metabolic syndrome, family history of diabetes, and follow-up duration were independent predictors of new-onset diabetes. CONCLUSION High-intensity statin treatment is associated with a higher risk of incident diabetes in prediabetic individuals, whereas the addition of ezetimibe to statin therapy has a neutral effect on glucose metabolism.

Reaching low density lipoprotein cholesterol targets

Abstract Cardiovascular disease is a major health problem and within the leading causes of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is strongly associated with the development and progression of cardiovascular disease and is among the main targets of lipid lowering therapy. Despite the various lipid lowering agents for the management of hyperlipidemia, a significant number of patients do not reach their LDL-C target goals. Data from studies in various world regions identify an often poor achievement of LDL-C goals, especially in high risk patient groups. The causes of this suboptimal management of hyperlipidemia are multifactorial and measures should be taken in order to identify and address these shortcomings in dyslipidemia therapy.

Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors to treat hypercholesterolemia: Effect on stroke risk

BACKGROUND/PURPOSE A reduction of cardiovascular events has been reported in phase 2 and 3 trials of the proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors alirocumab and evolocumab. We aimed to investigate the effect PCSK9 inhibition on stroke risk in a meta-analysis involving data from randomized studies with alirocumab and evolocumab. METHODS Data from pre-specified combined analysis of 4465 patients who completed phase 2 or 3 studies of evolocumab over a period of 1year and a randomized trial on alirocumab including 2341 patients with hyperlipidemia on maximally tolerated statin who were at high risk for coronary heart disease over a period of 1.5years were used. RESULTS The number of patients having an ischemic stroke was small in both trials. PCSK9 inhibition showed no significant effect on stroke rate (risk ratio 1.43; 95% CI, 0.45-4.57, p=0.55). No significant differences in stroke risk were evident when transient ischemic attacks were included in the analysis (risk ratio 0.65; 95% CI, 0.25-1.68, p=0.37). No hemorrhagic strokes were reported in either study. CONCLUSION Although a benefit towards reduction of cardiovascular events in the overall has been documented, longer exposure is warranted to be able to evaluate the effect on stroke risk.

High triglyceride levels alter the correlation of apolipoprotein B with low- and non-high-density lipoprotein cholesterol mostly in individuals with diabetes or metabolic syndrome

OBJECTIVE To assess the correlation of Apolipoprotein B (Apo-B) with low-density (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) in untreated individuals attending a lipid clinic. METHODS This was a retrospective study conducted in Greece and including 1000 dyslipidemic subjects. We included individuals not taking lipid-lowering therapy at baseline visit and divided them in 2 groups: subjects diagnosed with diabetes or fulfilling the criteria of metabolic syndrome (MetS) and hyperlipidemic subjects without diabetes or MetS. The correlations (r(2)) of Apo-B with LDL-C and non-HDL-C were assessed in these 2 groups. Further analyses were performed according to the baseline triglyceride (TG) levels (<and ≥200 mg/dL). RESULTS From 821 eligible subjects, 51% were diagnosed with diabetes or MetS. The correlations between Apo-B and LDL-C or non-HDL-C were similar for the individuals with TG < 200 mg/dL. Specifically, Apo-B was significantly correlated with LDL-C (r(2) = 0.755, p < 0.01, for those with diabetes or MetS; r(2) = 0.848, p < 0.01, for non-diabetic and no MetS hyperlipidemic subjects). The corresponding correlations between Apo-B and non-HDL-C for the 2 groups were 0.743 and 0.838, respectively (p < 0.01). Although these correlations remained significant for the individuals with high TG levels (≥200 mg/dL), the correlation factor was markedly decreased mostly in those with diabetes or MetS (r(2) = 0.600, p < 0.01, for the correlation between Apo-B and LDL-C; r(2) = 0.604, p < 0.01, for the correlation between Apo-B and non-HDL-C); in contrast, the corresponding correlations were stronger in the non-diabetic and no MetS hyperlipidemic individuals (r(2) = 0.710 and 0.714, respectively, p < 0.01). CONCLUSION Apo-B correlation with both LDL-C and non-HDL-C is reduced in individuals with high TG levels and in particular for those with diabetes or MetS.

The CHADS2 and CHA2DS2-VASc scores predict atrial fibrillation in dyslipidemic individuals: Role of incorporating low high-density lipoprotein cholesterol levels

AIM To investigate the value of CHADS2 and CHA2DS2-VASc scores in predicting atrial fibrillation (AF) among dyslipidemic individuals and assess the additional value of incorporating low levels of high-density lipoprotein cholesterol (HDL-C). METHODS This observational study included 1241 individuals attending a lipid clinic. Models including clinical and laboratory parameters were constructed to test the predictive value of CHADS2 and CHA2DS2-VASc scores as well as low HDL-C levels for incident AF. Low HDL-C levels were defined as <40 and <50mg/dL for male and female subjects, respectively. RESULTS After excluding 18 patients with AF at baseline, 1223 subjects were followed-up for a median period of 6years (IQR: 4-10), and 34 (2.8%) developed AF. Baseline CHADS2 (OR: 1.71; 95% CI: 1.28-2.29, p<0.001) and CHA2DS2-VASc scores (OR: 1.56; 95% CI: 1.26-1.92, p<0.001) as well as low HDL-C levels (OR: 3.79; 95% CI: 1.85-7.75, p<0.001) were significantly associated with new-onset AF. ROC curve analyses showed that both CHADS2 and CHA2DS2-VASc scores were significant predictors for new-onset AF (C-Statistic: CHADS2 0.679, p<0.001; CHA2DS2-VASc 0.698, p<0.001). Higher CHADS2 scores were associated with reduced event-free survival from AF (log-rank=10.62, p=0.001) with differences potentiated if stratified by CHA2DS2-VASc score (log-rank=22.29, p<0.001). After incorporating low HDL-C levels, both scores achieved slightly higher C-Statistic for AF prediction (0.690 and 0.707, respectively, p<0.001). CONCLUSIONS CHADS2 and CHA2DS2-VASc scores predict new AF in dyslipidemic patients. Risk prediction improved modestly when low HDL-C levels were included.

Attainment of multifactorial treatment targets among the elderly in a lipid clinic.

Objective To examine target attainment of lipid-lowering, antihypertensive and antidiabetic treatment in the elderly in a specialist setting of a University Hospital in Greece. Methods This was a retrospective study including consecutive subjects ≥ 65 years old (n = 465) with a follow-up ≥ 3 years. Low-density lipoprotein cholesterol (LDL-C), blood pressure (BP) and glycated hemoglobin (HbA1c) goal achievement were recorded according to European Society of Cardiology/European Atherosclerosis Society (ESC/EAS), European Society of Hypertension (ESH)/ESC and European Association for the Study of Diabetes (EASD) guidelines. Results The LDL-C targets were attained by 27%, 48% and 62% of very high, high and moderate risk patients, respectively. Those receiving statin + ezetimibe achieved higher rates of LDL-C goal achievement compared with those receiving statin monotherapy (48% vs. 33%, P < 0.05). Of the diabetic subjects, 71% had BP < 140/85 mmHg, while 78% of those without diabetes had BP < 140/90 mmHg. A higher proportion of the non-diabetic individuals (86%) had BP < 150/90 mmHg. Also, a higher proportion of those with diabetes had HbA1c < 8% rather than < 7% (88% and 47%, respectively). Of note, almost one out of three non-diabetic individuals and one out of ten diabetic individuals had achieved all three treatment targets. Conclusions Even in a specialist setting of a University Hospital, a high proportion of the elderly remain at suboptimal LDL-C, BP and HbA1c levels. The use of drug combinations could improve multifactorial treatment target attainment, while less strict targets could be more easily achieved in this population.