Is the metabolic syndrome a new childhood disease?

Overweight and obesity in children and adolescents have become a major public health problem in recent years throughout the world. The medical consequences of obesity may manifest as an increase in the prevalence of the metabolic syndrome in children and adolescents putting them at increased risk for future cardiovascular diseases. Obesity can cause insulin resistance and might disturb glucose homeostasis eventually leading to type 2 diabetes in susceptible patients. Insulin resistance is also involved in the pathogenesis of dyslipidemia in obese children characteristically presenting as hypertriglyceridemia and low HDL cholesterol. Even elevated blood pressure might be present in obese kids. Here we present a 12-year-old boy diagnosed with the metabolic syndrome. The diagnostic criteria of the metabolic syndrome in children and adolescents are discussed. Thoughts about pathophysiology and therapeutic options are offered.

Bacterial profile and burden of periodontal infection in subjects with a diagnosis of acute coronary syndrome

BACKGROUND: Periodontitis has been identified as a potential risk factor in cardiovascular diseases. It is possible that the stimulation of host responses to oral infections may result in vascular damage and the inducement of blood clotting. The aim of this study was to assess the role of periodontal infection and bacterial burden as an explanatory variable to the activation of the inflammatory process leading to acute coronary syndrome (ACS). METHODS: A total of 161 consecutive surviving cases admitted with a diagnosis of ACS and 161 control subjects, matched with cases according to their gender, socioeconomic level, and smoking status, were studied. Serum white blood cell (WBC) counts, high- and low-density lipoprotein (HDL/LDL) levels, high-sensitivity C-reactive protein (hsC-rp) levels, and clinical periodontal routine parameters were studied. The subgingival pathogens were assayed by the checkerboard DNA-DNA hybridization method. RESULTS: Total oral bacterial load was higher in the subjects with ACS (mean difference: 17.4x10(5); SD: 10.8; 95% confidence interval [CI]: 4.2 to 17.4; P<0.001), and significant for 26 of 40 species including Porphyromonas gingivalis, Tannerella forsythensis, and Treponema denticola. Serum WBC counts, hsC-rp levels, Streptococcus intermedius, and Streptococcus sanguis, were explanatory factors to acute coronary syndrome status (Nagelkerke r2=0.49). CONCLUSION: The oral bacterial load of S. intermedius, S. sanguis, Streptococcus anginosus, T. forsythensis, T. denticola, and P. gingivalis may be concomitant risk factors in the development of ACS.

Platelet collagen receptors: a new target for inhibition?

Collagen is a major component of extracellular matrix and a wide variety of types exist. Cells recognise collagen in different ways depending on sequence and structure. They can recognise predominantly primary sequence, they may require triple-helical structure or they can require fibrillar structures. Since collagens are major constituents of the subendothelium that determine the thrombogenicity of the injured or pathological vessel wall, a major role is induction of platelet activation and aggregation as the start of repair processes. Platelets have at least two direct and one indirect (via von Willebrand factor) receptors for collagen, and collagen has specific recognition motifs for these receptors. These receptors and recognition motifs are under intensive investigation in the search for possible methods to control platelet activation in vivo. A wide range of proteins has been identified and, in part, characterised from both haematophageous insects and invertebrates but also from snake venoms that inhibit platelet activation by collagen or induce platelet activation via collagen receptors on platelets. These will provide model systems to test the effect of inhibition of specific collagen-platelet receptor interactions for both effectiveness as well as for side effects and should provide assay systems for the development of small molecule inhibitors. Since platelet inhibitors for long-term prophylaxis of cardiovascular diseases are still in clinical trials there are many unanswered questions about long-term effects both positive and negative. The major problem which still has to be definitively solved about these alternative approaches to inhibition of platelet activation is whether they will show advantages in terms of dose-response curves while offering decreased risks of bleeding problems. Preliminary studies would seem to suggest that this is indeed the case.

Novel insight into the pathobiology of abdominal aortic aneurysm and potential future treatment concepts

The patient with abdominal aortic aneurysm (AAA) commonly is a nondiabetic, white man with a history of smoking. Moreover, AAA represents a leading cause of death in elderly men in Western countries. The purpose of this manuscript is to review current evidence as to the pathobiology of AAA as well as potential future drug targets to prevent progression of AAA.

Review of 197 consecutive free flap reconstructions in the lower extremity

Complications and failures after microvascular free tissue transfer for lower extremity reconstruction have a negative impact on postoperative course and final outcome. Therefore, a 10-year analysis on lower extremity reconstruction with free flaps was performed with a special emphasis on patient co-morbidities such as cardiovascular diseases, diabetes mellitus, body mass index and history of smoking, in order to identify potential risk factors. Complications such as haematoma, seroma, infection, wound dehiscence, as well as partial flap loss, postoperative thrombosis of the anastomosis and eventual total flap loss were gathered from the medical records. Limb salvage was 100%, however 40% suffered from complications ranging from minor wound dehiscence to total flap loss. None of the above-mentioned potential risk factors was associated with an increased rate of complications. However, in flaps that required revision for thrombosis, the age of the patients was significantly higher in the group of flaps that eventually failed when compared to flaps that were salvaged. In conclusion, lower extremity reconstruction with microvascular free tissue transfer is a safe and reliable procedure with a high success rate, however partial flap loss remains an important issue. Increased age was the only factor identified with an increased risk for subsequent flap loss in cases that were revised for thrombosis.

Metabolic predictors of inflammation, adhesion, and coagulability in healthy younger-aged adults

Elevated levels of inflammatory biomarkers are associated with the pathophysiology of cardiovascular diseases and are predictors of cardiovascular events. The objective of this study was to determine the unique contributions of metabolic factors as predictors of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)), adhesion (soluble intercellular adhesion molecule-1 (sICAM-1)), and coagulation (D-dimer) in healthy younger-aged adults. Participants were 83 women and 92 men (mean age 30.04 years, s.d. +/- 4.8, range 22-39) of normal weight to moderate obese weight (mean BMI 24.4 kg/m(2), s.d. +/- 3.35, range 17-32). The primary data analytical approaches included Pearson correlation and multiple linear regression. Circulating levels of CRP, IL-6, sICAM-1, and D-dimer were determined in plasma. Higher levels of CRP were independently associated with higher BMI, a greater waist-to-hip ratio, female gender, and higher triglycerides (P < 0.001). Higher IL-6 levels were independently associated with a greater waist-to-hip ratio (P < 0.01). Higher levels of sICAM-1 were independently associated with higher BMI, higher triglycerides, and lower insulin resistance (P < 0.001). Higher D-dimer levels were independently associated with higher BMI and being female (P < 0.001). Having a higher BMI was most consistently associated with elevated biomarkers of inflammation, adhesion, and coagulation in this sample of healthy younger-aged adults, although female gender, insulin resistance, and lipid levels were also related to the biomarkers. The findings provide insight into the adverse cardiovascular risk associated with elevated body weight in younger adults.

Flash pulmonary edema

Flash pulmonary edema (FPE) is a general clinical term used to describe a particularly dramatic form of acute decompensated heart failure. Well-established risk factors for heart failure such as hypertension, coronary ischemia, valvular heart disease, and diastolic dysfunction are associated with acute decompensated heart failure as well as with FPE. However, endothelial dysfunction possibly secondary to an excessive activity of renin-angiotensin-aldosterone system, impaired nitric oxide synthesis, increased endothelin levels, and/or excessive circulating catecholamines may cause excessive pulmonary capillary permeability and facilitate FPE formation. Renal artery stenosis particularly when bilateral has been identified has a common cause of FPE. Lack of diurnal variation in blood pressure and a widened pulse pressure have been identified as risk factors for FPE. This review is an attempt to delineate clinical and pathophysiological mechanisms responsible for FPE and to distinguish pathophysiologic, clinical, and therapeutic aspects of FPE from those of acute decompensated heart failure.

[The role of percutaneus coronary interventions in the treatment of coronary artery disease]

In industrial countries, cardiovascular diseases remain the primary cause of death. This review summarizes the role of percutaneous coronary interventions (PCI) in the treatment of coronary heart disease. Interventional therapy of coronary artery disease was initiated in 1977 with the introduction of balloon angioplasty by Andreas Grüntzig in Zurich. Technical progress since has been related to construction and materials of catheters, but also to digital processing of x-ray imaging. Additional methods - rotablation, atherectomy, laser, intravascular ultrasound, and most importantly stent implantation were developed. Only stents significantly changed the procedure. They are today an integral part of PCI.

[Gerodontology consultation in geriatric facilities: general health status (I)]

Dental undertreatment is often seen in the older population. This is particularly true for the elderly living in nursing homes and geriatric hospitals. The progression of chronic diseases results in loss of their independence. They rely on daily support and care due to physical or mental impairment. The visit of a dentist in private praxis becomes difficult or impossible and is a logistic problem. These elderly patients are often not aware of oral and dental problems or these are not addressed. The geriatric hospital Bern, Ziegler, has integrated dental care in the concept of physical rehabilitation of geriatric patients. A total of 139 patients received dental treatment in the years 2005/2006. Their mean age was 83 years, but the segment with > 85 years of age amounted to 46%. The general health examinations reveald multiple and complex disorders. The ASA classification (American Society of Anesthesiologists, Physical Status Classification System) was applied and resulted in 15% = P2 (mild systemic disease, no functional limitation), 47% = P3 (severe systemic disease, definite functional limitations) and 38% = P4 (severe systemic disease, constant threat to life). Eighty-seven of the patients exhibited 3 or more chronic diseases with a prevalence of cardiovascular diseases, musculoskelettal disorders and dementia. Overall the differences between men and women were small, but broncho-pulmonary dieseases were significantly more frequent in women, while men were more often diagnosed with dementia and depression. Verbal communication was limited or not possible with 60% of the patients due to cognitive impairment or aphasia after a stroke. Although the objective treatment need is high, providing dentistry for frail and geriatric patients is characterized by risks due to poor general health conditions, difficulties in communication, limitations in feasibility and lack of adequate aftercare. In order to prevent the problem of undertreatment, elderly independently living people should undergo dental treatment regularly and in time. Training of nurses and doctors of geriatric hospitals in oral hygiene should improve the awareness. A multidisciplinary assessment of geriatric patients should include the oral and dental aspect if they enter the hospital.

The effect of natural habituation on coagulation responses to acute mental stress and recovery in men

Blood coagulation activation might be one mechanism linking acute mental stress with coronary events. We investigated the natural habituation of coagulation responses and recovery to short-term mental stress. Three times with one-week intervals, 24 men (mean age 47 +/- 7 years) underwent the same 13-min stressor (preparation, job interview, mental arithmetic). During each visit venous blood was obtained four times (baseline, immediately post-stress, 45 min of recovery, 105 min of recovery). Eight blood coagulation parameters were measured at weeks one and three. Acute stress provoked increases in von Willebrand factor antigen, fibrinogen, clotting factor FVII activity (FVII:C), FVIII:C, FXII:C (p's < or = 0.019), and D-dimer (N.S.). All coagulation parameters experienced full recovery except FVIII:C (p = 0.022). Stress did not significantly affect activated partial thromboplastin time and prothrombin time. At all time points FVIII:C and FXII:C levels were significantly higher at week one compared to week three (p's < or = 0.041). Before catheter insertion, systolic blood pressure (p = 0.001) and heart rate (p = 0.026) were relatively higher at week one. Unlike the magnitude of systolic blood pressure response to stress (p = 0.007) and of cortisol recovery from stress (p = 0.002), the magnitude of all coagulation responses to stress and the recovery from stress were similar in week one and week three. Sympathetic activation with anticipatory stress best explained increased baseline activity in FVIII and FXII at week one. An incapacity of the coagulation system to adapt to stress repeats is perhaps a consequence of evolution, but might also contribute to increased coronary risk in some individuals, particularly in those with cardiovascular diseases.

Novel cell-free strategy for therapeutic angiogenesis: in vitro generated conditioned medium can replace progenitor cell transplantation

BACKGROUND: Current evidence suggests that endothelial progenitor cells (EPC) contribute to ischemic tissue repair by both secretion of paracrine factors and incorporation into developing vessels. We tested the hypothesis that cell-free administration of paracrine factors secreted by cultured EPC may achieve an angiogenic effect equivalent to cell therapy. METHODOLOGY/PRINCIPAL FINDINGS: EPC-derived conditioned medium (EPC-CM) was obtained from culture expanded EPC subjected to 72 hours of hypoxia. In vitro, EPC-CM significantly inhibited apoptosis of mature endothelial cells and promoted angiogenesis in a rat aortic ring assay. The therapeutic potential of EPC-CM as compared to EPC transplantation was evaluated in a rat model of chronic hindlimb ischemia. Serial intramuscular injections of EPC-CM and EPC both significantly increased hindlimb blood flow assessed by laser Doppler (81.2+/-2.9% and 83.7+/-3.0% vs. 53.5+/-2.4% of normal, P<0.01) and improved muscle performance. A significantly increased capillary density (1.62+/-0.03 and 1.68+/-0.05/muscle fiber, P<0.05), enhanced vascular maturation (8.6+/-0.3 and 8.1+/-0.4/HPF, P<0.05) and muscle viability corroborated the findings of improved hindlimb perfusion and muscle function. Furthermore, EPC-CM transplantation stimulated the mobilization of bone marrow (BM)-derived EPC compared to control (678.7+/-44.1 vs. 340.0+/-29.1 CD34(+)/CD45(-) cells/1x10(5) mononuclear cells, P<0.05) and their recruitment to the ischemic muscles (5.9+/-0.7 vs. 2.6+/-0.4 CD34(+) cells/HPF, P<0.001) 3 days after the last injection. CONCLUSIONS/SIGNIFICANCE: Intramuscular injection of EPC-CM is as effective as cell transplantation for promoting tissue revascularization and functional recovery. Owing to the technical and practical limitations of cell therapy, cell free conditioned media may represent a potent alternative for therapeutic angiogenesis in ischemic cardiovascular diseases.

Cell-based therapy facilitates venous thrombus resolution

Endothelial progenitor cells (EPC) are involved in many healing processes in cardiovascular diseases and can be found in spontaneously resolving venous thrombi. The purpose of the present study was to investigate whether the therapeutic administration of EPC might enhance the resolution of venous thrombi. For this purpose, venous thrombosis was induced in the infrarenal inferior vena cava (IVC) in 28 athymic nude rats. Culture expanded EPC derived from human peripheral blood mononuclear cells were injected intravenously two and four days after thrombus induction. Recanalisation of the IVC and thrombus organisation were assessed by laser Doppler measurements of the blood flow and immunohistochemical detection of endothelialised luminal structures in the thrombus. EPC transplantation resulted in significantly enhanced thrombus neovascularisation (capillary density: 186.6 +/- 26.7/HPF vs. 78 +/- 12.3/HPF, p<0.01; area covered by capillaries: 8.9 +/- 1.7 microm(2) vs. 2.5 +/- 1.3 microm(2), p<0.01) and was accompanied by a substantial increase in intra-thrombus blood flow (perfusion ratio: 0.7 +/- 0.07 vs. 0.3 +/- 0.08, p<0.02). These results were paralleled by augmented macrophage recruitment into resolving thrombi in the animals treated with EPC (39.4 +/- 4.7/HPF vs. 11.6 +/- 1.9/HPF, p<0.01). Our data suggest that EPC transplantation might be of clinical value to facilitate venous thrombus resolution in cases where current therapeutic options have limited success.

Renal resistance index in renal allograft recipients: a role for ADMA

BACKGROUND: Renal resistance index, a predictor of kidney allograft function and patient survival, seems to depend on renal and peripheral vascular compliance and resistance. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and therefore influences vascular resistance. STUDY DESIGN: We investigated the relationship between renal resistance index, ADMA, and risk factors for cardiovascular diseases and kidney function in a cross-sectional study. SETTING ; PARTICIPANTS: 200 stable renal allograft recipients (133 men and 67 women with a mean age of 52.8 years). PREDICTORS: Serum ADMA concentration, pulse pressure, estimated glomerular filtration rate and recipient age. OUTCOME: Renal resistance index. MEASUREMENTS: Renal resistance index measured by color-coded duplex ultrasound, serum ADMA concentration measured by liquid chromatography-tandem mass spectrometry, estimated glomerular filtration rate (Nankivell equation), arterial stiffness measured by digital volume pulse, Framingham and other cardiovascular risk factors, and evaluation of concomitant antihypertensive and immunosuppressive medication. RESULTS: Mean serum ADMA concentration was 0.72 +/- 0.21 (+/-SD) micromol/L and mean renal resistance index was 0.71 +/- 0.07. Multiple stepwise regression analysis showed that recipient age (P < 0.001), pulse pressure (P < 0.001), diabetes (P < 0.01) and ADMA concentration (P < 0.01) were independently associated with resistance index. ADMA concentrations were correlated with estimated glomerular filtration rate (P < 0.01). LIMITATIONS: The cross-sectional nature of this study precludes cause-effect conclusions. CONCLUSIONS: In addition to established cardiovascular risk factors, ADMA appears to be a relevant determinant of renal resistance index and allograft function and deserves consideration in prospective outcome trials in renal transplantation.

Experience and attitudes towards CAM--a survey of internal and psychosomatic patients in a German university hospital

Complementary and alternative medicine (CAM) is popular in Germany. In a consecutive survey the experiences with CAM and the need for a CAM consultation among inpatients of the departments of cardiology (CL), gastroenterology (GE), oncology (OL) and psychosomatics (PS) of the University Hospital Freiburg (FUH) were questionned. Exclusion criteria were inability to understand the questions or a Karnofsky Index < 30%. Four hundred thirty-five patients were included. Three hundred and fifty patients, 100 each in the departments of CL, GE and OL, and 50 in PS answered the questionnaires. Eighty-five patients (20%) refused. Among the 350 patients 26% had previously visited a CAM physician and 19% had visited a CAM therapist (Heilpraktiker). Information about CAM was obtained mainly by television, radio and family members. Frequently used therapies for the current disease were physical training (21%), diet (19%), massage (19%), vitamins/trace elements (19%), herbs (13%), acupuncture (10%) and homeopathy (7%). The highest frequency of CAM use had PS patients, followed by GE, OL and CL patients. High effectivity (> or = 70%) for the current disease, rated on a scale of 4 degrees, had for CL patients physical exercise and massage, for GE patients herbal treatment and for OL patients diet. Physical exercise, diet, massage and herbal treatment generally had better ratings than homeopathy, acupuncture and vitamins. 65% would welcome a CAM center and 53% asked for a consultation about CAM at FUH. OL and GE patients had the strongest (58%), PS patients a lower (52%) and patients with cardiovascular diseases the lowest (43%) interest in a CAM consultation. Twenty-five percent believed, that CAM can help to cope better with their disease. Predictors for a positive attitude towards CAM were young age, aversion to chemical medications (Spearman correlation r = 0.22), desire to participate in therapeutic decisions (r = 0.29), motivation to change, if recommended, the life style (r = 0.31) and desire for a holistic treatment (r = 0.37).

Differential effects of captopril and nitrates on muscle sympathetic nerve activity in volunteers

BACKGROUND The sympathetic nervous system (SNS) is an important regulator of cardiovascular function. Activation of SNS plays an important role in the pathophysiology and the prognosis of cardiovascular diseases such as heart failure, acute coronary syndromes, arrhythmia, and possibly hypertension. Vasodilators such as adenosine and sodium nitroprusside are known to activate SNS via baroreflex mechanisms. Because vasodilators are widely used in the treatment of patients with cardiovascular diseases, the aim of the present study was to assess the influence of clinically used dosages of isosorbide dinitrate and captopril on sympathetic nerve activity at rest and during stimulatory maneuvers. METHODS AND RESULTS Twenty-eight healthy volunteers were included in this double-blind placebo-controlled study, and muscle sympathetic nerve activity (MSA; with microelectrodes in the peroneal nerve), blood pressure, heart rate, and neurohumoral parameters were measured before and 90 minutes after the oral administration of 40 mg isosorbide dinitrate or 6.25 mg captopril. Furthermore, a 3-minute mental stress test and a cold pressor test were performed before and 90 minutes after drug administration. Resting MSA did not change after captopril and decreased compared with placebo (P < .05 versus placebo), whereas isosorbide dinitrate led to a marked increase in MSA (P < .05). Systolic blood pressure was reduced by isosorbide dinitrate (P < .05), whereas captopril decreased diastolic blood pressure (P < .05). The increases in MSA, blood pressure, and heart rate during mental stress were comparable before and after drug administration regardless of the medication. During cold pressor test, MSA and systolic and diastolic blood pressures increased to the same degree independent of treatment, but after isosorbide dinitrate, the increase in MSA seemed to be less pronounced. Heart rate did not change during cold stimulation. Plasma renin activity increased after captopril and isosorbide dinitrate (P < .05), whereas placebo had no effect. Endothelin-1 increased after placebo and isosorbide dinitrate (P < .05) but not after captopril. CONCLUSIONS Thus, captopril suppressed MSA despite lowering of diastolic blood pressure but allowed normal adaptation of the SNS during mental or physical stress. In contrast, the nitrate strongly activated the SNS under baseline conditions. These findings demonstrate that vasodilators differentially interact with the SNS, which could be of importance in therapeutic strategies for the treatment of patients with cardiovascular diseases.