Early Manifestations Of Cardiovascular Disease Research Articles

Pediatric hypertension as an early manifestation of cardiovascular disease in children

RESUMO Em adultos, eventos cardiovasculares associados à hipertensão arterial (HA) apresentam grande repercussão na morbimortalidade. À luz dos novos conhecimentos, a HA na criança tem sido interpretada como doença cardiovascular (DCV) precoce, enquanto a exposição da criança aos fatores de risco CV revela-se preditora de DCV subclínica em adultos. As classificações da medida de pressão arterial (PA) no adulto e na faixa pediátrica foram recentemente atualizadas pelo American College of Cardiology/American Heart Association. A HA primária na criança é em geral assintomática, e se associa com história familiar de HA, sobrepeso/obesidade e normalidade morfofuncional do sistema urinário. Quanto mais jovem a criança e mais elevada a PA, maior a chance de se tratar de HA secundário. A investigação da etiologia da HA inicia-se com anamnese detalhada, que deve incluir informações clínicas e de utilização de medicamentos, fumo e álcool, desde o período perinatal até o momento da consulta. A modificação de fatores de risco, com redução do peso, redução do consumo de álcool e aumento do consumo de vegetais, entre a infância e a idade adulta, mostrou associação com a resolução da HA na transição infância-idade adulta e com a reversão dos efeitos adversos cardiometabólicos nos indivíduos adultos não obesos. A terapêutica farmacológica deve ser iniciada para casos de HA sintomática, HA secundária a doença renal crônica ou a diabetes mellitus, presença de lesões de órgão alvo, HA estágio 2 sem causa modificável e HA persistente não responsiva à mudança de estilo de vida.

Pediatric hypertension as an early manifestation of cardiovascular disease in children.

In adults, cardiovascular events associated with arterial hypertension (AH) have a major impact on morbidity and mortality. In light of recent findings, AH in children has been interpreted as early cardiovascular disease (CVD), while exposure to CV risk factors in children proves to be a predictor of subclinical CVD in adults. The American College of Cardiology/American Heart Association has recently updated the classifications for measuring blood pressure (BP) in adults and children. Primary AH in children is generally asymptomatic, and it is associated with a family history of AH, overweight/obesity, and normal morphofunctional characteristics of the urinary system. The younger the child and the higher the BP, the greater the likelihood of secondary AH. The investigation into the etiology of AH begins with a detailed anamnesis, which should include clinical information and details on the use of medication, smoking, and alcohol consumption from the perinatal period to the time of consultation. Modifying risk factors by reducing weight, decreasing alcohol consumption and increasing vegetable intake from childhood to adulthood has been associated with the resolution of AH in the childhood-adulthood transition, and with the reversal of cardiometabolic adverse effects in non-obese adult individuals. Pharmacological therapy should be initiated in cases of symptomatic AH, AH secondary to chronic kidney disease or diabetes mellitus, presence of target organ lesions, stage 2 AH with no modifiable cause and resistant AH unresponsive to lifestyle changes.

Early vascular aging as an index of cardiovascular risk in healthy adults: confirmatory factor analysis from the EVasCu study

BackgroundThe concept of early vascular aging (EVA) represents a potentially beneficial model for future research into the pathophysiological mechanisms underlying the early manifestations of cardiovascular disease. For this reason, the aims of this study were to verify by confirmatory factor analysis the concept of EVA on a single factor based on vascular, clinical and biochemical parameters in a healthy adult population and to develop a statistical model to estimate the EVA index from variables collected in a dataset to classify patients into different cardiovascular risk groups: healthy vascular aging (HVA) and EVA.MethodsThe EVasCu study, a cross-sectional study, was based on data obtained from 390 healthy adults. To examine the construct validity of a single-factor model to measure accelerated vascular aging, different models including vascular, clinical and biochemical parameters were examined. In addition, unsupervised clustering techniques (using both K-means and hierarchical methods) were used to identify groups of patients sharing similar characteristics in terms of the analysed variables to classify patients into different cardiovascular risk groups: HVA and EVA.ResultsOur data show that a single-factor model including pulse pressure, glycated hemoglobin A1c, pulse wave velocity and advanced glycation end products shows the best construct validity for the EVA index. The optimal value of the risk groups to separate patients is K = 2 (HVA and EVA).ConclusionsThe EVA index proved to be an adequate model to classify patients into different cardiovascular risk groups, which could be valuable in guiding future preventive and therapeutic interventions.

Association of circulating MtDNA with CVD in hemodialysis patients and in vitro effect of exogenous MtDNA on cardiac microvascular inflammation

BackgroundChronic kidney disease (CKD) patients sustain a fairly high prevalence of cardiovascular disease (CVD). Microvascular inflammation is an early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been proposed to be a crucial integrator of inflammatory signals. Herein, the aim of this study was to determine the relationship between CVD, microvessel, and circulating MtDNA in the settings of uremia.MethodsForty-two maintenance hemodialysis (MHD) patients and 36 health controls were enrolled in this study. Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), fibrinogen, and erythrocyte sedimentation rate (ESR) were measured by standard assays. Ten-year CVD risk was calculated from the Framingham risk score (FRS) model. In vitro study, human cardiac microvascular endothelial cells (HCMECs) were incubated with normal or uremic serum, with or without exogenous MtDNA. Intracellular toll-like receptor 9 (TLR9), adhesion molecule 1 (ICAM-1), MCP-1 and tumor necrosis factor-α (TNF-α) and cytosolic MtDNA were detected by qPCR.ResultsPlasma MtDNA in MHD patients was significantly higher than healthy controls (4.74 vs. 2.41 × 105 copies/mL; p = 0.000). Subsequently, the MHD patients were classified into two groups based on the MtDNA median (4.34 × 105 copies/mL). In stratified analyses, the levels of Hs-CRP (5.02 vs. 3.73 mg/L; p = 0.042) and MCP-l (99.97 vs. 64.72 pg/mL; p = 0.008) and FRS (21.80 vs. 16.52; p = 0.016) in the high plasma MtDNA group were higher than those in the low plasma MtDNA group. In vitro study, we found that exogenous MtDNA aggravated uremic serum-induced microvascular inflammation (ICAM-1 and TNF-α) in HCMECs (all p < 0.05). Besides, the addition of MtDNA to the medium resulted in a further increase in cytosolic MtDNA and TLR9 levels in uremic serum-treated cells (all p < 0.05). In patients with MHD, MtDNA levels in plasma were significantly reduced after a single routine hemodialysis (pre 4.47 vs. post 3.45 × 105 copies/mL; p = 0.001) or hemodiafiltration (pre 4.85 vs. post 4.09 × 105 copies/mL; p = 0.001). These two approaches seem similar in terms of MtDNA clearance rate (21.26% vs. 11.94%; p = 0.172).ConclusionsOverall, the present study suggests that MtDNA released into the circulation under the uremic toxin environment may adversely affect the cardiovascular system by exacerbating microvascular inflammation, and that reducing circulating MtDNA might be a future therapeutic strategy for the prevention of MHD-related CVD.

Effects of microsomal prostaglandin E synthase-1 inhibition on resistance artery tone in patients with end stage kidney disease.

The microvasculature is a target organ for the early manifestations of cardiovascular disease. Therefore, a better understanding of the prostaglandin system and characterising the effects of mPGES-1 inhibition and concomitant reduction of PGE2 in vascular beds are of interest. The effects of mPGES-1 inhibition on constriction and relaxation of resistance arteries (diameter: 100-400 μm) from patients with end stage kidney disease (ESKD) and controls (Non-ESKD) were studied using wire-myography in combination with immunological and mass-spectrometry based analyses. Inhibition of mPGES-1 in arteries from ESKD patients and Non-ESKD controls significantly reduced adrenergic vasoconstriction, which was unaffected by the COX-2 inhibitors NS-398 and Etoricoxib, or by the COX-1/COX-2 inhibitor Indomethacin tested in Non-ESKD controls. However, a significant increase of acetylcholine-induced dilatation was observed for mPGES-1 inhibition. In IL-1β treated arteries, inhibition of mPGES-1 significantly reduced PGE2 levels while PGI2 levels remained unchanged. In contrast, COX-2 inhibition blocked the formation of both prostaglandins. Blockade of PGI2 signalling with an IP receptor antagonist did not restore the reduced adrenergic constriction, neither did blocking PGE2 -EP4 or signalling through PPARγ. A biphasic effect was observed for PGE2 , inducing dilatation at nanomolar and constriction at micromolar concentrations. Immunohistochemistry demonstrated expression of mPGES-1, COX-1, PGIS, weak expression for COX-2, as well as receptor expression for PGE2 (EP1-4), thromboxane (TP) and PGI2 (IP) in ESKD and Non-ESKD. Our study demonstrates vasodilating effects following mPGES-1 inhibition in human microvasculature and suggests that several pathways besides shunting to PGI2 are involved.

Relationship between the state coagulation system, protein and fat metabolism, and Brain iron deposition in patients with cerebral small vessel disease

Brain iron deposition correlates with clinical manifestations of cerebral small vessel disease. Excessive iron load leads to the formation of free radicals, and nervous tissue damage. The main damaging effect of hydroxyl radicals is due to conversion of soluble fibrinogen to insoluble fibrin. There is also a possible relationship between the functional state of the liver and the early manifestations of cardiovascular disease. Objective: to investigate the relationship between the parameters of coagulation system, liver functional state, fat and protein metabolism, and brain iron deposition in patients with cerebral small vessel disease in the presence of hypertension and cerebral atherosclerosis. Materials and methods: 80 patients with diagnosed cerebral small vessel disease were selected. Patients were divided into two groups, depending on the severity of brain iron deposition. All patients underwent MRI in the T1-WI, T2-WI, TIRM, DWI, and SWI sequences. Determination of the coagulation system parameters and the biochemical analysis were carried out during routine blood test. Results: using a double-sample t test, it was determined that patients with severe brain iron deposition had higher levels of urea, triglycerides, and prolonged thrombin time. With the logistic regression analysis adjusted by the age and sex, levels of urea and the length of thrombin time were determined as the independent risk factors for severe brain iron deposition. For urea OR 1.87, CI 95% 1.31-2.65 (p = 0.02), for thrombin time OR 1.55, CI 95% 1.06-2.26 (p = 0.02). For these parameters, the risk increased when assessing only patients with ALT levels&gt; 15 U / l. For such patients, the relationship between thrombin time and brain iron deposition increased significantly: OR 2.11, CI 95% 1.20-3.71 (p = 0.01). In this study no relationship was found between the indicators of fat metabolism, levels of fibrin and iron deposition. There is a probable relationship between the brain iron deposition and the state of coagulation system, protein metabolism and liver functional state in patients with cerebral small vessel disease.

Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis

Chronic kidney disease (CKD) is associated with excessive mortality from cardiovascular disease (CVD). Endothelial dysfunction, an early manifestation of CVD, is consistently observed in CKD patients and might be linked to structural defects of the microcirculation including microvascular rarefaction. However, patterns of microvascular rarefaction in CKD and their relation to functional deficits in perfusion and oxygen delivery are currently unknown. In this in-vivo microscopy study of the cremaster muscle microcirculation in BALB/c mice with moderate to severe uremia, we show in two experimental models (adenine feeding or subtotal nephrectomy), that serum urea levels associate incrementally with a distinct microangiopathy. Structural changes were characterized by a heterogeneous pattern of focal microvascular rarefaction with loss of coherent microvascular networks resulting in large avascular areas. Corresponding microvascular dysfunction was evident by significantly diminished blood flow velocity, vascular tone, and oxygen uptake. Microvascular rarefaction in the cremaster muscle paralleled rarefaction in the myocardium, which was accompanied by a decrease in transcription levels not only of the transcriptional regulator HIF-1α, but also of its target genes Angpt-2, TIE-1 and TIE-2, Flkt-1 and MMP-9, indicating an impaired hypoxia-driven angiogenesis. Thus, experimental uremia in mice associates with systemic microvascular disease with rarefaction, tissue hypoxia and dysfunctional angiogenesis.

Deterioration of Chronotropic Responses and Heart Rate Recovery Indices in Men With Erectile Dysfunction.

IntroductionErectile dysfunction (ED) and cardiovascular (CV) diseases share common risk factors and ED has been accepted as an early manifestation of CV disease. Exercise stress testing (EST) is used to evaluate CV functions in men with ED. Low exercise workload, a slower heart rate recovery (HRR) after exercise, and inability to increase heart rate during EST (chronotropic incompetence) are independent negative predictors of adverse CV outcomes.AimTo assess the association among EST parameters, ED, and testosterone levels.MethodsThe study population consisted of 41 patients with ED and 40 controls. All participants underwent treadmill EST to assess cardiac autonomic functions. HRR indices were calculated by subtracting 1st (HRR1), 2nd (HRR2), and 3rd (HRR3) minute heart rates during the recovery period from maximal heart rate. Total exercise duration, exercise capacity and chronotropic response, and plasma testosterone levels were evaluated. Erectile functions were evaluated with the Sexual Health Inventory for Men. Patients were divided into subgroups according to severity and duration of ED.Main Outcome MeasuresMean HRR1 (30.6 ± 11.9 vs 36.9 ± 9.9; P = .01), HRR2 (44.9 ± 12.4 vs 54.9 ± 7.8; P < .001), and HRR3 (50.1 ± 11.7 vs 63.0 ± 7.9; P < .001) were significantly lower in the ED than in the control group. Total exercise duration (9.4 ± 1.9 vs 10.9 ± 1.7 minutes; P < .001), exercise capacity (12.5 ± 1.9 vs 13.6 ± 1.4 metabolic equivalents; P = .004), and chronotropic response (0.88 ± 0.1 vs 1.0 ± 0.1; P < .001) were worse in the ED group. However, we found no association between severity and duration of ED and EST parameters. In addition, serum testosterone levels were significantly correlated with HRR1 (r = 0.36, P = .02) in men with ED.ConclusionOur data suggested that cardiac autonomic functions are impaired in patients with ED. A weak correlation between cardiac autonomic dysfunction and low testosterone levels in patients with ED was noted. However, further studies are needed to elucidate the prognostic significance and clinical implications of impaired autonomic functions and testosterone replacement therapy in patients with ED.Kucukdurmaz F, Agar G, Resim S. Deterioration of Chronotropic Responses and Heart Rate Recovery Indices in Men With Erectile Dysfunction. Sex Med 2018;6:8–14.

255 - Deterioration of chronotropic responses and heart rate recovery indices in men with erectile dysfunction

Abstract Introduction Erectile dysfunction (ED) and cardiovascular (CV) diseases share common risk factors and ED has been accepted as an early manifestation of CV disease. Exercise stress testing (EST) is used to evaluate CV functions in men with ED. Low exercise workload, a slower heart rate recovery (HRR) after exercise, and inability to increase heart rate during EST (chronotropic incompetence) are independent negative predictors of adverse CV outcomes. Aim To assess the association among EST parameters, ED, and testosterone levels. Methods The study population consisted of 41 patients with ED and 40 controls. All participants underwent treadmill EST to assess cardiac autonomic functions. HRR indices were calculated by subtracting 1st (HRR1), 2nd (HRR2), and 3rd (HRR3) minute heart rates during the recovery period from maximal heart rate. Total exercise duration, exercise capacity and chronotropic response, and plasma testosterone levels were evaluated. Erectile functions were evaluated with the Sexual Health Inventory for Men. Patients were divided into subgroups according to severity and duration of ED. Main Outcome Measures Mean HRR1 (30.6 ± 11.9 vs 36.9 ± 9.9; P = .01), HRR2 (44.9 ± 12.4 vs 54.9 ± 7.8; P P P P = .004), and chronotropic response (0.88 ± 0.1 vs 1.0 ± 0.1; P P = .02) in men with ED. Conclusion Our data suggested that cardiac autonomic functions are impaired in patients with ED. A weak correlation between cardiac autonomic dysfunction and low testosterone levels in patients with ED was noted. However, further studies are needed to elucidate the prognostic significance and clinical implications of impaired autonomic functions and testosterone replacement therapy in patients with ED. Kucukdurmaz F, Agar G, Resim S. Deterioration of Chronotropic Responses and Heart Rate Recovery Indices in Men With Erectile Dysfunction. Sex Med 2018;6:8–14.

Reduced Microvascular Density in Omental Biopsies of Children with Chronic Kidney Disease.

BackgroundEndothelial dysfunction is an early manifestation of cardiovascular disease (CVD) and consistently observed in patients with chronic kidney disease (CKD). We hypothesized that CKD is associated with systemic damage to the microcirculation, preceding macrovascular pathology. To assess the degree of “uremic microangiopathy”, we have measured microvascular density in biopsies of the omentum of children with CKD.Patients and MethodsOmental tissue was collected from 32 healthy children (0–18 years) undergoing elective abdominal surgery and from 23 age-matched cases with stage 5 CKD at the time of catheter insertion for initiation of peritoneal dialysis. Biopsies were analyzed by independent observers using either a manual or an automated imaging system for the assessment of microvascular density. Quantitative immunohistochemistry was performed for markers of autophagy and apoptosis, and for the abundance of the angiogenesis-regulating proteins VEGF-A, VEGF-R2, Angpt1 and Angpt2.ResultsMicrovascular density was significantly reduced in uremic children compared to healthy controls, both by manual imaging with a digital microscope (median surface area 0.61% vs. 0.95%, p<0.0021 and by automated quantification (total microvascular surface area 0.89% vs. 1.17% p = 0.01). Density measured by manual imaging was significantly associated with age, height, weight and body surface area in CKD patients and healthy controls. In multivariate analysis, age and serum creatinine level were the only independent, significant predictors of microvascular density (r2 = 0.73). There was no immunohistochemical evidence for apoptosis or autophagy. Quantitative staining showed similar expression levels of the angiogenesis regulators VEGF-A, VEGF-receptor 2 and Angpt1 (p = 0.11), but Angpt2 was significantly lower in CKD children (p = 0.01).ConclusionsMicrovascular density is profoundly reduced in omental biopsies of children with stage 5 CKD and associated with diminished Angpt2 signaling. Microvascular rarefaction could be an early systemic manifestation of CKD-induced cardiovascular disease.

CARDIOVASCULAR LESIONS IN CHILDREN WITH OBESITY

The dominance of cardiovascular diseases in the structure of mortality and disability in developed countries as well as the increasing incidence of cardiovascular disorders led to development of conception of cardiovascular continuum based on the clinical evaluation of the risk factors for cardiovascular complications. In this regard studying of the initial stages of this process, i. e. childhood and adolescence, is of great interest. It is now apparent that childhood obesity may be regarded as a cardiovascular risk factor in adulthood. This fact also corresponds to the accumulated information on the cardiovascular disease in children and adolescents with obesity and its similarity with the changes found in adults. What also facilitates the importance of this issue is a steady worldwide increase of the percentage of infants with excess body weight, which may lead to possible increase in cardiovascular disease in the near future. The review covers early manifestations of cardiovascular disease in children with obesity, the development of endothelial dysfunction, remodeling of the artery wall and the progression of atherosclerotic lesions in the aorta and peripheral vessels. The review addresses the distinction of the hypertension development and course as well as the indication of cardiac remodeling and diagnostic criteria of left ventricular hypertrophy. The review provides directions in prevention and treatment of cardiovascular changes in children and adolescents with obesity.

School burnout and cardiovascular functioning in young adult males: a hemodynamic perspective

This study investigated aortic and brachial hemodynamic functioning that may link school burnout to cardiovascular risk factors. Methodological improvements from previous research were implemented including (1) statistical control of depressive and anxiety symptoms (2) resting, stress-induced and cardiac recovery condition comparisons and (3) use of pulse wave analysis. Forty undergraduate young adult males completed self-report measures of school burnout, trait anxiety and depressive symptoms. Participants then completed a protocol consisting of a 10-min seated rest, 5-min baseline (BASE), 3-min cold pressor test (CPT) and a 3-min recovery period (REC). Indices of brachial and aortic hemodynamics were obtained by means of pulse wave analysis via applanation tonometry. Controlling for anxiety and depressive symptoms, planned contrasts identified no differences in cardiovascular parameters at BASE between participants in burnout and non-burnout groups. However, negative changes in hemodynamic indices occurred in burnout participants at CPT and REC as evidenced by increased aortic and brachial systolic and diastolic blood pressures, increased left ventricular work and increased myocardial oxygen consumption. Findings suggest that school burnout symptoms are associated with cardiac hyperactivity during conditions of cardiac stress and recovery and therefore may be associated with the early manifestations of cardiovascular disease. Future studies are suggested to reveal underlying autonomic mechanisms explaining hemodynamics functioning in individuals with school burnout symptomatology.

Classical cardiovascular disease risk factors associate with vascular function and morphology in rheumatoid arthritis: a six-year prospective study

IntroductionPatients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease (CVD). An early manifestation of CVD is endothelial dysfunction which can lead to functional and morphological vascular abnormalities. Classical CVD risk factors and inflammation are both implicated in causing endothelial dysfunction in RA. The objective of the present study was to examine the effect of baseline inflammation, cumulative inflammation, and classical CVD risk factors on the vasculature following a six-year follow-up period.MethodsA total of 201 RA patients (155 females, median age (25th to 75th percentile): 61 years (53 to 67)) were examined at baseline (2006) for presence of classical CVD risk factors and determination of inflammation using C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). At follow-up (2012) patients underwent assessments of microvascular and macrovascular endothelium-dependent and endothelium-independent function, along with assessment of carotid atherosclerosis. The CRP and ESR were recorded from the baseline study visit to the follow-up visit for each patient to calculate cumulative inflammatory burden.ResultsClassical CVD risk factors, but not RA disease-related inflammation, predicted microvascular endothelium-dependent and endothelium-independent function, macrovascular endothelium-independent function and carotid atherosclerosis. These findings were similar in a sub-group of patients free from CVD, and not receiving non-steroidal anti-inflammatory drugs, cyclooxygenase 2 inhibitors or biologics. Cumulative inflammation was not associated with microvascular and macrovascular endothelial function, but a weak association was apparent between area under the curve for CRP and carotid atherosclerosis.ConclusionsClassical CVD risk factors may be better long-term predictors of vascular function and morphology than systemic disease-related inflammation in patients with RA. Further studies are needed to confirm if assessments of vascular function and morphology are predictive of long-term CV outcomes in RA.

The Growing Epidemic of Hypertension Among Children and Adolescents: A Challenging Road Ahead

Currently, it is clear that primary hypertension begins in childhood and that it contributes to the early development of chronic kidney disease (CKD). Hypertension also increases the risk of cardiovascular morbidity and mortality, and that risk rises as blood pressure levels escalate. As among adult patients, overweight and obesity rates are on the rise among children and adolescents with primary hypertension and can develop target organ damage including left ventricular hypertrophy. An elevated level of C-reactive protein (CRP) and microalbuminuria are early manifestations of cardiovascular disease and CKD in hypertensive patients. Lifestyle interventions are recommended for all children with hypertension. Pharmacologic therapy should be added for symptomatic children, those with stage 2 hypertension, and children with prehypertension and stage 1 hypertension who exhibit an insufficient response to lifestyle modifications. Although the recommendations for choice of drugs generally are similar for children and adults, dosages for children should be lower, based on weight, and adjusted very carefully. Medications that are effective and safe for children and adolescents include thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and calcium channel-blockers. Hypertension is not being detected early enough for initiation of a treatment regimen to reduce death and disability. Initiatives should be undertaken to make health care providers and the general population more aware of the seriousness of hypertension in children and adolescents. This review focuses on the principles underlying the importance of a team approach for hypertension control, especially one that incorporates increased data sharing using enhanced health information technology for early detection and intervention.

Early Origins of Cardiovascular Disease in Pediatric Chronic Kidney Disease

The importance of cardiovascular disease in adults with chronic kidney disease is now well recognized. For children who develop chronic kidney disease, cardiovascular disease is also a leading cause of eventual morbidity and mortality. Although the clinical manifestations of cardiovascular disease may not be apparent until later, early subclinical findings can be observed even during childhood. This review updates the reader on the epidemiology of cardiovascular disease in pediatric chronic kidney disease, discusses risk factors and potential mechanisms of accelerated cardiovascular disease, reviews evidence of early manifestations of cardiovascular disease in pediatric chronic kidney disease, and briefly discusses prevention and treatment strategies.

Shift Work and Arteriosclerosis Risk in Professional Bus Drivers

Professional bus drivers are at increased risk for cardiovascular disease, but the underlying causes are unclear. Professional bus drivers often follow shift schedules. Especially, an association between shift work and early manifestations of cardiovascular disease has not been elucidated. Thus we investigated the links between shift work and arteriosclerosis risk in professional bus drivers. Questionnaires were administered to 184 bus drivers on demographic characteristics, lifestyle, and occupational history from 5 transportation companies in Taiwan. Brachial-ankle pulse wave velocity (baPWV) was measured using a volume-plethysmographic apparatus. Body mass index, waist circumference, biochemical variables, and blood pressure were also measured. Arteriosclerotic risk factors (age, weekly driving hours, systolic blood pressure, diastolic blood pressure, and insulin level) differed in part among different groups of drivers. Long-term shift drivers had higher baPWV compared to regular drivers and short-term shift drivers (1594 cm/s vs. 1497 and 1432, p<0.01). Our multiple regression model showed that age (p<0.01) and diastolic blood pressure (p<0.01) were positively associated with baPWV in our professional drivers. After adjusting for all covariates, we observed that baPWV increased by 3.6 cm/s for per 1-year increment in years of shift driving. Long-term shift work could increase the risk of arteriosclerosis in professional bus drivers. Larger studies would be necessary to provide further evidence regarding this finding.

Clinical Implications of the DREAM Study

In response to an article (1) published in 2003 demonstrating that both diet and exercise as well as pioglitazone reduced insulin resistance in upper-body obese, sedentary, nondiabetic individuals, I wrote an editorial (2) discussing whether the treatment of insulin resistance independent of any effect on glycemia could be beneficial for reducing the risk of cardiovascular disease (CVD). At that time, evidence for a beneficial effect rested on surrogate end points and intermediate outcomes of CVD. The final sentence in the editorial was, “If the ongoing clinical trials demonstrate a reduction in hard clinical events, difficult decisions will need to be made.” Although thiazolidinediones (TZDs) continued to lower many of the surrogate risk factors associated with and early manifestations of CVD (e.g., endothelial dysfunction, intima medial thickness of carotid arteries) in subsequent studies, the effect on preventing hard clinical outcomes in the first clinical trial reported was less robust than many had anticipated (3). Now the Diabetes Reduction Assessment with Rampipril and Rosiglitazone Medication (DREAM) study (4) has been published, raising the question of treating nondiabetic individuals with a TZD, to reduce the risk of developing type 2 diabetes rather than CVD. The DREAM study (4) randomized over 5,000 individuals with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) to receive either 8 mg rosiglitazone or placebo over a median of 3 years. There was an ∼60% less chance of those receiving the TZD to develop diabetes compared with those receiving the placebo. For every 1,000 subjects with IFG and/or IGT given rosiglitazone, 144 would be prevented from developing diabetes. There would be, however, four to five excess cases (i.e., over what would have occurred if a TZD had not been given) of heart failure. In addition to the small increase in heart failure, the cost of the TZD …

Patient characteristics rather than the type of dialyser predict the variability of endothelial derived surface molecules in chronic haemodialysis patients

Cardiovascular disease (CVD) is a frequent complication in chronic haemodialysis (HD) patients. Endothelial dysfunction, as measured by soluble cellular adhesion molecules (sCAM) and von Willebrand factor (vWf) in plasma, is an early manifestation of CVD. Today, it is unknown if, and to what extent, their levels are influenced by the type of dialyser. Four dialysers, low-flux cuprammonium (CU); high-flux and low-flux polysulfone and super-flux polyethersulfone, were compared in 15 chronic HD patients in a randomized cross-over fashion. sCAM and vWf were measured at baseline as well as after 4 weeks, and both intra-dialytical and after 24 h (t24 h). Twenty healthy subjects served as controls. Baseline levels were considerably higher in chronic HD patients than in controls (soluble intercellular adhesion molecule-1: sICAM-1 732+/-216 vs 572+/-259 ng/ml, P = 0.06; soluble vascular cell adhesion molecule-1: sVCAM-1 1917+/-492 vs 1126+/-338 ng/ml, P<0.001; vWF: 205+/-55% vs 98+/-52%, P<0.001). After 4 weeks, no changes were observed. During and after HD, sCAM did not change, except in the case of CU (sICAM-1: 719+/-259 to 772+/-261 ng/ml, P = 0.04). CU induced a rise in vWF directly after HD (t4 h; from 188+/-48% to 255+/-92%, P<0.01), whereas all modalities induced a significant increase at t24 h (mean 228+/-54%, P = 0.02). The levels of sCAM and vWf appeared to be dependent on the individual patients rather than on the type of dialyser (explained variance by different patients: 66%-91%, P<0.001; by type of dialyser 0.4-1.2%). Baseline levels of sCAM and vWf were markedly higher in chronic HD patients than in controls and did not change after 4 weeks with any dialyser. All membranes induced a marked rise in vWf at t24 h, whereas sICAM-1 increased only in the case of CU at t4 h. As sCAM showed no marked changes during HD with any other modality, our study suggests activation of blood cells rather than endothelial cells. As pre-dialysis levels of sCAM and vWf varied noticeably between individual patients, endothelial dysfunction seems to be far more dependent on patient-related factors than on the HD treatment itself.

Impaired quality of life as a risk factor in cardiovascular disease

Traditionally, quality of life has been considered a major outcome variable in the study of patients with chronic disease or handicap. In this paper, impaired quality of life is analyzed as a risk, that is, a condition influencing early manifestation of cardiovascular disease. Specific social contexts as well as a psychological coping style (need for control) that generates sustained emotional distress are defined, and data from two socio-epidemiological studies are presented. The first is a retrospective case-control study of 380 men with a first myocardial infarction. The second is a prospective study of 416 middle-aged blue-collar workers followed over 3 years. Findings show that indicators of impaired quality of life are related to high levels of cardiovascular risk factors and high prevalence of overt cardiovascular disease. Practical implications point to the importance of a socio-behavioral approach in cardiovascular prevention.