Cardiovascular Disease in Patients with Chronic Obstructive Pulmonary Disease, Obstructive Sleep Apnoea Syndrome and Overlap Syndrome.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea syndrome (OSAS) are among the most prevalent chronic respiratory disorders. Accumulating data suggest that there is a significant burden of cardiovascular disease (CVD) in patients with COPD and OSAS, affecting negatively patients' quality of life and survival. Overlap syndrome (OS), i.e. the co-existence of both COPD and OSAS in the same patient, has an additional impact on the cardiovascular system multiplying the risk of morbidity and mortality. The underlying mechanisms for the development of CVD in patients with either OSAS or COPD and OS are not entirely elucidated. Several mechanisms, in addition to smoking and obesity, may be implicated, including systemic inflammation, increased sympathetic activity, oxidative stress and endothelial dysfunction. Early diagnosis and proper management of these patients might reduce cardiovascular risk and improve patients' survival. In this review, we summarize the current knowledge regarding epidemiological aspects, pathophysiological mechanisms and present point-to-point specific associations between COPD, OSAS, OS and components of CVD, namely, pulmonary hypertension, coronary artery disease, peripheral arterial disease and stroke.

Peripheral vascular changes in the lower limbs following cocaine abuse.

Background: Worldwide, substance use disorder is on the rise, especially amongst the young generation. Although cocaine-induced cardiovascular and cerebrovascular events are well documented, knowledge about the relationship of cocaine use and its effect on arterial perfusion in the lower limbs is scarce.Objective: This study sought to investigate the relationship between cocaine use and peripheral arterial disease.Methods: The study population comprised 30 subjects' dependent on cocaine, smoking and alcohol [Group A] and another 30 subjects dependent on smoking and alcohol only [Group B]. A comprehensive lower limb vascular assessment was conducted utilizing pulse palpation, Doppler spectral waveform analysis, Ankle brachial pressure index (ABPI) and Toe brachial pressure index (TBPI) to determine the arterial perfusion status in the lower limbs.Results: Group A had lower ABPIs and TBPIs than Group B suggesting poorer vascular perfusion in lower limbs. Furthermore, a larger percentage of Group A had monophasic/continuous waveforms of all three pedal pulses compared to Group B. Conversely there was a higher percentage in Group B with biphasic/triphasic waveforms compared to Group A implying better vascular perfusion.Conclusion: In this study, cocaine use was associated with diminished arterial perfusion of the lower limbs suggesting that cocaine use has the potential to increase the risk of peripheral arterial disease. Regular vascular foot screening is warranted if foot complications are to be avoided.

Correlation of cardiac autonomic neuropathy with small and large peripheral nerve function in type 2 diabetes mellitus.

AIMS: To analyse the correlation of cardiac autonomic neuropathy (CAN), sympathetic and parasympathetic dysfunction with the different diagnostic tools for large and small peripheral nerve fibres in type 2 diabetes mellitus (T2DM). METHODS: We included 153 T2DM subjects (92 men) with mean age of 64.4 years. CAN, as well as sympathetic and parasympathetic dysfunction were diagnosed by the Ewing's cardiovascular reflex tests. Vibration perception threshold (VPT), monofilament, Ipswich Touch test, automated sural nerve conduction study and neuropathy disability score (NDS) evaluated large and small peripheral nerve fibre function. RESULTS: CAN (adjusted odds ratio [aOR]: 44.57), parasympathetic (aOR: 18.40) and sympathetic dysfunction (aOR: 5.50) correlated with measures of small fibre function evaluated by pinprick sensation and temperature perception. Among tools for large nerve fibres, positive correlation was shown between: (1) CAN and abnormal VPT (aOR: 16.78), (2) parasympathetic dysfunction and abnormal VPT (aOR: 39.47). CONCLUSIONS: CAN and parasympathetic dysfunction correlate with peripheral neuropathy, especially when the latter is assessed through VPT and measures of small fibre function as evaluated by pinprick sensation and temperature perception. The latter additionally correlate with sympathetic nervous system impairment.

Vitamin D Levels in Middle-Aged Patients with Obstructive Sleep Apnoea Syndrome.

BACKGROUND: Vitamin D (Vit D) insufficiency has been implicated in the pathophysiology of numerous diseases. Obstructive sleep apnoea syndrome (OSAS), a disorder associated with increased cardiovascular and cerebrovascular morbidity, has been associated with decreased Vit D levels, but reports are inconclusive. AIM: To evaluate the association between serum 25-hydroxyvitamin D [25(OH)D], a marker of Vit D status, with anthropometric and sleep characteristics of OSAS patients and to compare those levels between OSAS patients and non-apnoeic controls. METHOD: Consecutive subjects who had undergone polysomnography and pulmonary function testing were divided into controls (apnoea-hypopnea index, AHI <5/h) and OSAS group (AHI ≥5/h). RESULTS: A total of 169 subjects (135 men) were included. OSAS patients (n=139) significantly differed from non-apnoeic controls in terms of age (53.9±12.8 vs. 44.9±12.8 years, p=0.002) and body mass index (BMI) (35.9±6.9 vs. 29.9±6.8 kg/m2, p<0.001). Serum 25(OH)D levels were lower in OSAS patients (17.8±7.8 vs. 23.9±12.4 ng/ml, p=0.019). In OSAS patients, levels of serum 25(OH)D were negatively correlated with sleep stage transitions (r=-0.205, p=0.028), AHI (r=-0.187, p=0.045), oxygen desaturation index (r=-0.234, p=0.011) and percentage of time with oxyhaemoglobin saturation <90% (r=-0.172, p=0.041). In contrast, they were positively correlated with average oxyhaemoglobin saturation during sleep (r=0.179, p=0.033), forced expiratory volume in 1 sec (r=0.207, p=0.037) and oxygen partial pressure (r=0.197, p=0.029). CONCLUSION: Vit D levels were lower in OSAS patients compared with non-apnoeic controls. Several indices of OSAS severity also correlated with Vit D levels.

Oral Glucose-lowering Drugs and Cardiovascular Outcomes: From the Negative RECORD and ACCORD to Neutral TECOS and Promising EMPA-REG.

BACKGROUND: Cardiovascular (CV) morbidity and mortality are higher among patients with diabetes mellitus type 2 (T2DM), particularly those with concomitant CV diseases, compared with other populations. In patients with T2DM, intensive glucose lowering reduces microvascular disease, but has a smaller and debated effect on CV events or mortality. In this setting, the US Food and Drug Administration (FDA) required in 2008 that all new agents for the treatment of T2DM should be evaluated in terms of CV safety. Metformin has long been established as first-line pharmacological therapy in patients with T2DM, due to its proven beneficial CV effects. Despite the controversies about the issue of the CV safety of other oral antidiabetic agents such as sulfonylureas (SUs) and thiazolidinediones (TZDs), long-term randomized trials suggested neutral effects of these agents on macrovascular disease. Moreover, there are a number of CV outcome trials designed to determine the long-term CV safety of new glucose-lowering agents, like dipeptidyl peptidase 4 (DPP-4) inhibitors, and sodium glucose cotransporter 2 (SGLT2) inhibitors. Although the results of these trials indicate the CV safety of oral new antidiabetic agents, only one of them (with empagliflozin) has so far reported reduction of CV events. Recently, LEADER (Liraglutide Effect And Action in Diabetes: Evaluation of Cardiovascular Outcome Results - A Long-term Evaluation), a CV outcome trial in diabetic patients by using an injectable glucose-lowering agent (liraglutide) has also reported a reduction in CV outcomes. CONCLUSION: The present review considers the long-term CV effects of anti-diabetic drugs and updates the relevant randomized CV outcome studies of oral glucose-lowering agents.

Family History of Type 2 Diabetes: Does Having a Diabetic Parent Increase the Risk?

BACKGROUND: It is well established that there is an important genetic predisposition for type 2 diabetes mellitus (T2DM). OBJECTIVE: To summarise available epidemiological data regarding T2DM transmission in various populations. METHOD: Narrative review. RESULTS: The estimated risk for the diagnosis of T2DM increases approximately by 2-4 times, when father, mother or both have this condition. Conversely, many T2DM patients have family members with DM. Studies have suggested that the likelihood of T2DM in the next generation is higher in the event of a diabetic mother than father. Both genetic factors, such as mitochondrial DNA mutations, and environmental components, such as intra-uterine environment, have been implicated in the higher maternal transmission of T2DM. Despite the above findings, some studies in populations with high frequency of T2DM have not corroborated the predominantly maternal transmission. Such works have shown either an excess paternal or an equal transmission of T2DM. CONCLUSION: It appears that potential biases in reporting family history data, especially between the various racial groups, have contributed to the controversy over the existence of excess maternal transmission of DM.

Insulin Sensitivity and Insulin Resistance in Non-Diabetic Middle-Aged Patients with Obstructive Sleep Apnoea Syndrome.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) has been linked with abnormal glucose metabolism, insulin resistance (IR) and development of diabetes mellitus. METHODS: Non-diabetic patients (n=69) with OSAS, diagnosed by polysomnography, were prospectively recruited. To evaluate IR among OSAS patients, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Insulin sensitivity by Quantitative Insulin sensitivity Check Index (QUICKI) were used. RESULTS: HOMA-IR was positively associated with body-mass index (BMI) (ρ=0.364, p=0.002), time with oxyhaemoglobin saturation <90% (ρ=0.291, p=0.015), arousal index (ρ=0.268, p=0.027), Epworth sleepiness scale (ESS) score (ρ=0.293, p=0.019) and negatively with average oxyhaemoglobin saturation (ρ=-0.398, p=0.001) and minimum oxyhaemoglobin saturation (ρ=-0.327, p=0.006). QUICKI was positively associated with forced vital capacity (r=0.301, p=0.014), average oxyhaemoglobin saturation (r=0.443, p<0.001), minimum oxyhaemoglobin saturation (ρ=0.318, p=0.008), and negatively associated with sleep stage transitions (r=-0.266, p=0.032), oxygen desaturation index (r=-0.404, p=0.005), time with oxyhaemoglobin saturation <90% (r=-0.311, p=0.019), arousal index (r=-0.344, p=0.004) and ESS score (r=-0.299, p=0.016). After adjustment for age and BMI, HOMA-IR was associated with sleep stage transitions, time with oxyhaemoglobin saturation <90%, average oxyhaemoglobin saturation, minimum oxyhaemoglobin saturation and arousal index. QUICKI was associated with oxygen desaturation index, sleep stage transitions, ESS score, minimum oxyhaemoglobin saturation and arousal index. CONCLUSIONS: An independent association between OSAS and IR in patients without pre-existing diabetes mellitus was observed. Recurrent hypoxia and sleep fragmentation in OSAS are associated with IR in these patients.

The potential of SGLT2 inhibitors in phase II clinical development for treating type 2 diabetes.

INTRODUCTION: There is now an abundance of anti-diabetic agents. However, only few patients achieve glycemic targets. Moreover, current glucose-lowering agents mainly depend upon insulin secretion or function. Sodium glucose co-transporter type 2 (SGLT2) inhibitors present a novel glucose-lowering therapy, inducing glycosuria in an insulin-independent fashion. AREAS COVERED: In this review, the authors discuss the key efficacy and safety data from phase II clinical trials in type 2 diabetes mellitus (T2DM) of the main SGLT2 inhibitors approved or currently in development, and provide a rationale for their use in T2DM. EXPERT OPINION: Despite the very promising characteristics of this new therapeutic class, a number of issues await consideration. One important question is what to expect from head-to-head comparison data. We also need to know if dual inhibition of SGLT1/SGLT2 is more efficacious in reducing HbA1c and how this therapy affects metabolic and cardiovascular parameters. Additionally, several SGLT2 agents that have not yet come to market have hitherto been evaluated in Asian populations, whereas approved SGLT2 inhibitors have been frequently studied in other populations, including Caucasian subjects. Thus, we need more information on the potential role of ethnicity on their efficacy and safety.

Mean Platelet Volume as a Surrogate Marker for Platelet Activation in Patients With Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with a prothrombotic state. AIM: To study mean platelet volume (MPV) and Platelet Distribution Width (PDW) as markers of platelet activation and their potential association with lung function in patients with recently diagnosed IPF. MATERIALS AND METHODS: This study included 56 patients with IPF (age 64.9±7.4 years) and 79 controls (age 64.2 ± 5.9 years). RESULTS: An inverse relation was demonstrated between platelet count and MPV in the control group but not among patients with IPF. Platelet count was significantly lower in patients with IPF compared with controls (230 ± 60 vs 256 ± 75 × 10(3)/µL, P = .038). Conversely, MPV was higher in patients versus controls (10.3 ± 1.2 vs 9.8 ± 1.2 fl, P = .024), while there was no difference between the groups in PDW. Respiratory function was, as expected, significantly impaired in patients with IPF versus controls in terms of forced expiratory volume in first second (FEV1; 67.2 ± 23.1 vs 102.6 ± 15.9% of predicted value, P < .001), forced vital capacity (FVC; 65.3 ± 21 vs 95.2 ± 16.1% of predicted value, P < .001), FEV1/FVC (83.1 ± 15 vs 87.5 ± 6.4%, P = .041) and partial pressure of oxygen in arterial blood (PaO2; 67.1 ± 10.3 vs 81.5 ± 15.2 mm Hg, P < .001). No significant correlation was seen between MPV and FVC (r = -.1497, P = .275), MPV and lung diffusion capacity for carbon monoxide (r = .035, P = .798) and total lung capacity (r = .032, P = .820). CONCLUSIONS: Patients with IPF exhibit higher MPV values and lower platelet count. Further studies are needed to assess the clinical implications of these findings.

Retinol Binding Protein-4 and Adiponectin Levels in Thyroid Overt and Subclinical Dysfunction.

Thyroid dysfunction is accompanied by numerous changes in intermediary metabolism. Retinol binding protein-4 (RBP-4) and adiponectin are 2 adipocytokines that have multiple metabolic functions. The aim of our study was to examine serum RBP4 and adiponectin levels in clinical (before and after therapy) and subclinical hyperthyroid and hypothyroid subjects as compared to controls.150 patients with thyroid dysfunction were recruited (65 hyperthyroid and 85 hypothyroid) while 28 euthyroid subjects served as a control group. We measured anthropometric, biochemical and hormonal (free T4, free T3, TSH, insulin) parameters in all participants. RBP-4 and adiponectin were measured using commercial ELISA kits.Mean baseline levels of RBP-4 were higher in patients with clinical hypothyroidism (29.0±10.2 ng/ml, 25.1±12.6 ng/ml, 38.8±16.5 ng/ml, 31.9±13.2 ng/ml, 20.4±8.2 ng/ml in patients with hyperthyroidism, subclinical hyperthryrodism, hypothyroidism, subclinical hypothyroidism and controls respectively, F=4.86, P<0.001) and decreased significantly in patients with clinical hyperthyroidism and hypothyroidism after normalization of thyroid hormones' levels (from 29.0±10.2 to 24.9±8.4 ng/ml, p=0.003 and from 38.8±16.5 to 29.0±10.8 ng/ml, p=0.001 respectively). We did not observe analogous changes in adiponectin levels in any of the studied groups.RBP-4 levels are higher in patients with clinical hypothyroidism and exhibit a marked decrease after normalization of thyroid function in both hyper and hypothyroid patients. We suggest that RBP-4 may play a role in the metabolic disturbances which accompany thyroid dysfunction.

Small-Fiber Neuropathy: A Diabetic Microvascular Complication of Special Clinical, Diagnostic, and Prognostic Importance.

Damage of small nerve fibers may lead to a large variety of clinical symptoms. Small-fiber neuropathy underlies the symptoms of painful diabetic neuropathy, which may decrease quality of life. It also contributes to the poor prognosis of diabetic neuropathy because it plays a key role in the pathogenesis of foot ulceration and autonomic neuropathy. Impairment of small nerve fibers is considered the earliest alteration in the course of diabetic neuropathy. Therefore, assessment of functional and morphological abnormalities of small nerve fibers may enable timely diagnosis. The definition, symptoms, and clinical significance of small-fiber neuropathy are considered in the present review. An apparently more complex interaction between small-fiber impairment and microcirculation is extensively discussed. Diagnostic modalities include morphometric and functional methods. Corneal confocal microscopy and punch skin biopsy are considered gold standards, but noninvasive functional tests are also diagnostically useful. However, in routine clinical practice, small-fiber neuropathy is diagnosed by its typical clinical presentation. Finally, prompt treatment should be initiated following diagnosis.