Presence Of Common Risk Factors Research Articles

Assessment of common risk factors of diabetes and chronic kidney disease: a Mendelian randomization study.

The increasing prevalence of diabetes and its significant impact on mortality and morbidity rates worldwide has led to a growing interest in understanding its common risk factors, particularly in relation to chronic kidney disease (CKD). This research article aims to investigate the shared risk factors between type 1 diabetes (T1D), type 2 diabetes (T2D), and CKD using a Mendelian randomization (MR) design. The study utilized genome-wide association study (GWAS) datasets for T1D, T2D, and CKD from the FinnGen research project. GWAS summary statistics datasets for 118 exposure traits were obtained from the IEU OpenGWAS database. MR analyses were conducted to examine the causal relationships between exposure traits and each of the three outcomes. Multiple methods, including inverse-variance weighted, weighted median, and MR-Egger, were employed for the MR studies. Phenome-wide MR analyses revealed that eosinophil percentage exhibited a significant and suggestive causal association with T1D and CKD, respectively, suggesting its potential as a shared risk factor for T1D and CKD. For T2D, 34 traits demonstrated significant associations. Among these 34 traits, 14 were also significantly associated with CKD, indicating the presence of common risk factors between T2D and CKD, primarily related to obesity, height, blood lipids and sex hormone binding globulin, blood pressure, and walking pace. This research has uncovered the eosinophil percentage as a potential common risk factor for both T1D and CKD, while also identifying several traits, such as obesity and blood lipids, as shared risk factors for T2D and CKD. This study contributes to the understanding of the common risk factors between diabetes and CKD, emphasizing the need for targeted interventions to reduce the risk of these diseases.

The effects of different knee osteoarthritis criteria on trail‐making test times in an elderly Malaysian cohort

AbstractBackgroundKnee osteoarthritis (KOA) is a common cause of morbidity among older people with its prevalence expected to increase with population ageing. The relationship between KOA and cognitive performance, however, is not well understood despite both conditions sharing common risk factors including age and metabolic syndrome. We evaluated the cognitive performance of individuals with and without KOA to evaluate this relationship.MethodData is from the Promoting Independence in our Seniors with Arthritis (PISA) study, which is comprised older adults with and without KOA recruited from an urban tertiary hospital and its catchment population. Basic demographics, physical and psychosocial characteristics were recorded. Cognitive performance was determined using the Trail‐Making Test (TMT). KOA was defined using the American College of Rheumatology (ACR) criteria, presence of knee pain, self‐reported physician diagnosis (SRPD), and the Kellgren‐Lawrence’s (KL) radiographic criteria. Multiple linear regression models were created and bootstrapping was used for Kellgren‐Lawrence in view of the smaller sample who had radiographic investigations.ResultTwo‐hundred and thirty participants, mean (SD) age of 66.93 (7.12) years, were recruited. KOA was present in 120 (58.0%), 94 (40.9%), 85 (39.9%), and 33 (57.9%) according to ACR, knee pain, SRPD and KL criteria respectively. TMT‐A scores were variably influenced by age, gender, years of education, grip strength, functional reach and presence of metabolic syndrome using the four KOA criteria. TMT‐B scores were influenced by age, gender, years of education, grip strength and depression scores differentially using the four KOA criteria. No significant associated was observed between KOA and TMT‐A or TMT‐B scores after adjustment for the potential confounders above.ConclusionKnee OA was not associated with differences in cognitive performance evaluated with TMT which is a cognitive screening tool which mainly evaluates attention, working memory and executive function. The presence of KOA did not influence TMT performance in this study, which suggests that KOA does not affect the above cognitive domains regardless of criteria for diagnosis. This suggests that cognitive impairment and KOA do not share common pathological processes despite the presence of common risk factors.

Синдром перекреста функциональной диспепсии и синдрома раздраженного кишечника: современные представления о патогенезе и возможностях медикаментозной коррекции

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) overlap is an adverse clinical case, which is associated with clinical manifestation aggravation of each of the diseases and a significant life quality reduction. Comorbidity occurrence in functional gastrointestinal disorders (FGID) is due to the presence of common risk factors and pathogenetic mechanisms. This review is aimed at systematization of the available data on the FGID etiopathogenesis. The role of genetic factors, nervous control, in particular n. vagus, providing afferent and efferent interaction between intestine and brain, as well as infectious agents that cause the low-grade inflammation preservation in the intestinal mucosa, is considered. The article also shows the role of mast cell mediators that alter gastrointestinal motility and secretion. The role of Helicobacter pylori in the formation of FGID is considered separately. The importance of a detailed diagnosis during the examination of patients with FGID was noted to exclude serious organic pathology with similar symptoms. The main methods of correction in the conditions of FD and IBS comorbidity are indicated. KEYWORDS: overlap syndrome, functional dyspepsia, irritable bowel syndrome, inflammation, comorbidity. FOR CITATION: Livzan M.A., Lisovskiy M.А., Gaus O.V. Irritable bowel syndrome and functional dyspepsia overlap: modern ideas concerning the pathogenesis and drug correction opportunities. Russian Medical Inquiry. 2023;7(7):439–444 (in Russ.). DOI: 10.32364/2587-6821-2023-7-7-6.

Фенотип СРК, ассоциированный с ожирением и избыточной массой тела: стратегия индивидуализированной курации больного

One of the most urgent problems of modern healthcare in Russia and worldwide is the increase in the number of people with overweight and obesity. It is generally recognized that overweight and obesity increase the risk of coronary heart disease, hypertension, type 2 diabetes mellitus, cholelithiasis, non-alcoholic fatty liver disease (NAFLD). At the same time, recent data indicate that pathomorphism of other chronic non-infectious diseases was also noted during preserving trend towards an increase in the obesity prevalence, for which the presence of overweight or obesity was not considered a traditional risk factor. Using the example of a clinical case concerning a female patient with a combined course of irritable bowel syndrome (IBS) and NAFLD, the article presents up-to-date information on risk factors and pathogenetic mechanisms of such comorbidity and suggests treatment methods to improve the therapy efficacy for this patient cohort. The presence of common risk factors and pathogenetic mechanisms creates the basis for the formation of comorbidity of IBS and NAFLD, which requires the development of patient-centered management. KEYWORDS: irritable bowel syndrome, non-alcoholic fatty liver disease, metabolic syndrome, intestinal permeability, intestinal microbiota, mebeverin, ademetionine. FOR CITATION: Livzan M.A., Gaus O.V., Fedorin M.M. IBS phenotype associated with obesity and overweight: treatment tactics for patient- centered management. Russian Medical Inquiry. 2023;7(5):323–331 (in Russ.). DOI: 10.32364/2587-6821-2023-7-5-11.

Hypertension in pregnancy as an early sex-specific risk factor for cardiovascular diseases: evidence and awareness.

Despite being a physiological condition, human pregnancy is known to cause numerous complications that can endanger the life of the mother and the fetus alike. While the majority of complications are mostly limited within the peripartum period, more and more information is available about persistently higher short- and long-term cardiovascular risk after a pregnancy complicated by a hypertensive disorder. There is evidence that women after gestational hypertension or preeclampsia are more likely to develop arterial hypertension, coronary atherosclerosis, myocardial infarction, stroke, peripheral artery disease, and even diabetes mellitus and venous thromboembolism years after the target pregnancy. This has urged some authors to view hypertensive disorders of pregnancy as a "stress test" for the maternal organism that unmasks latent endothelial dysfunction. An explanation is sought in the presence of common risk factors and underlying pathological pathways with cardiovascular diseases, although a certain etiological mechanism for the development of hypertensive disorders in pregnancy has not been established yet. More attention is needed towards the follow-up of women after a hypertensive pregnancy as it could be an opportunity for early prevention of cardiovascular diseases.

Індексна оцінка стану тканин пародонта у хворих з атеросклерозом

The purpose of the study was to assess the condition of periodontal tissues using periodontal indices in patients with generalized periodontitis on the background of atherosclerosis. Materials and methods. In the course of the dental study, we examined 232 patients (202 – patients with generalized periodontitis on the background of atherosclerosis (main group), and 30 patients with generalized periodontitis without somatic diseases (control group), aged 45-65 years, with a percentage ratio of men to women 65.5% and 34.5%, respectively. To establish the diagnosis (generalized periodontitis) the classification of periodontal tissue diseases edited by Danilevsky M. F. was used. Index assessment of periodontal tissue was determined using: papillary-marginal-alveolar index (Massler M., 1949, modified by Parma), periodontal index (Russel A. L., 1956), gingiva bleeding index (Muhlemann H. R., Mazor A. S., 1958, Cowell I., 1975). The loss of epithelial attachment was measured with a graduated probe and expressed in millimetres: the condition of the furcation of multi-rooted teeth was assessed in the horizontal direction by the method of Hemp, in the vertical – by the method of Tarnow-Fletcher. To study the degree and nature of resorption of the interalveolar septa of the bone of the alveolar processes, X-ray examination was performed using panoramic radiography and evaluated according to the Fuch X-ray index (Rtg). Results and discussion. Analysis of data from the modern literature shows that cardiovascular pathology can be considered as a risk factor for periodontal disease. On the other hand, there is convincing evidence that periodontal disease, in particular, its etiological factor – periodontal pathogens, directly affects the occurrence of changes in the cardiovascular system. This relationship is also evidenced by some epidemiological studies. According to Tonetti M. S., the connection between atherosclerosis and periodontal pathology is confirmed by the presence of common risk factors, in particular, generalized periodontitis induces systemic inflammation, which leads to the development of endothelial dysfunction, which is considered the basis of the pathogenesis of atherosclerosis. It was found that in patients with generalized periodontitis on the background of atherosclerosis, the average value of the papillary-marginal-alveolar index was 53.23±2.87%, p <0.05, and the Muellemann-Cowell index (gingiva bleeding index) was 2.53±0.25 points, p >0.05, which was by 1.2 times higher than the values in patients with generalized periodontitis without somatic diseases (44.27±2.57% and 2.10±0.29 points, respectively). In the main group, the values of periodontal indices and loss of epithelial attachment were by 1.3 times higher than the values in the comparison group (2.78±0.13 points, and 3.48±0.22 mm, against 2.06±0.09 points, 2.09±0.12 and 2.69±0.19 mm, p <0.05). In this case, the average value of Rtg – recession index of the gums in patients with atherosclerosis did not differ from those in persons without somatic diseases of the comparison group (1.36±0.12 points and 1.43±0.12 points, respectively, p >0.05). Conclusion. Thus, our results indicate a progressive course of generalized periodontitis in patients with atherosclerosis

Fibroblast Growth Factor-23-Klotho Axis in Cardiorenal Syndrome: Mediators and Potential Therapeutic Targets.

Cardiorenal syndrome (CRS) is a complex disorder that refers to the category of acute or chronic kidney diseases that induce cardiovascular disease, and inversely, acute or chronic heart diseases that provoke kidney dysfunction. There is a close relationship between renal and cardiovascular disease, possibly due to the presence of common risk factors for both diseases. Thus, it is well known that renal diseases are associated with increased risk of developing cardiovascular disease, suffering cardiac events and even mortality, which is aggravated in those patients with end-stage renal disease or who are undergoing dialysis. Recent works have proposed mineral bone disorders (MBD) as the possible link between kidney dysfunction and the development of cardiovascular outcomes. Traditionally, increased serum phosphate levels have been proposed as one of the main factors responsible for cardiovascular damage in kidney patients. However, recent studies have focused on other MBD components such as the elevation of fibroblast growth factor (FGF)-23, a phosphaturic bone-derived hormone, and the decreased expression of the anti-aging factor Klotho in renal patients. It has been shown that increased FGF-23 levels induce cardiac hypertrophy and dysfunction and are associated with increased cardiovascular mortality in renal patients. Decreased Klotho expression occurs as renal function declines. Despite its expression being absent in myocardial tissue, several studies have demonstrated that this antiaging factor plays a cardioprotective role, especially under elevated FGF-23 levels. The present review aims to collect the recent knowledge about the FGF-23-Klotho axis in the connection between kidney and heart, focusing on their specific role as new therapeutic targets in CRS.

CARDIOVASCULAR COMPLICATIONS OF ANTITUMOR THERAPY FOR BREAST CANCER: DIAGNOSIS, PREVENTION AND TREATMENT

Although significant advances have been made in breast cancer treatment resulting in improved survival, cardiovascular disease has become the main cause of disability and mortality not related to cancer recurrence. In the general population, cardiovascular disease is the leading cause of death in both women and men. In patients with breast cancer, the incidence of cardiovascular diseases is even higher than in the general population. The high incidence of cardiovascular disease in breast cancer patients is likely due to the presence of common risk factors as well as the patients with breast cancer, the incidence of cardiovascular diseases is even higher than in the general population. The high incidence of cardiovascular disease in breast cancer patients is likely due to the presence of common risk factors as well as cardiotoxicity of anticancer therapy. The rise in the development of cardiovascular disease in breast cancer survivors is a major concern. This literature review will describe the incidence of cardiovascular complications with different treatment regimens for breast cancer, risk factors for their development, strategies for monitoring cardiovascular function during and after anticancer therapy, and strategies for the prevention and treatment of cardiotoxicity.

Atrial fibrillation and cognitive impairment: cerebral microbleeds as a new risk factor and possibilities of anticoagulant therapy (Part 2)

Atrial fibrillation (AF) and cognitive impairment (CI) are among the most important problems of the modern health care system, which are characterized by an extremely high prevalence with the increasing trend of the latter; they lead to lower quality of life, shorter duration, and a larger number of disabled people. The specific feature of AF and CI is the presence of common risk factors. To date, the data of an increasing number of studies allow cerebral microbleeds (CMBs) to be considered as a new risk factor for CI, inter alia in patients with AF. In recent years, special attention has been paid to the role of oral anticoagulants (OACs) in the prevention of CI in AF, which is reflected in a number of studies and meta-analyses. In terms of the effect of OACs on the risk of CMBs, there is reason to believe that the latter increases with the use of warfarin, the effects of direct OACs (DOAC) in this regard require further investigation. At the same time, among the DOACs, apixaban is the only drug that has been proven to have no negative effect on the risk of CMBs in a randomized controlled clinical trial. In general, the available data indicate the positive effect of OACs in reducing the risk of CI and dementia in AF; moreover, DOACs have an advantage in this respect. Among the DOACs, apixaban is promising due to its optimal efficacy and safety profile.

РАСПРОСТРАНЕННОСТЬ МОДИФИЦИРУЕМЫХ ФАКТОРОВ РИСКА В ПОПУЛЯЦИИ У ПАЦИЕНТОВ С САХАРНЫМ ДИАБЕТОМ, В ТОМ ЧИСЛЕ С СИНДРОМОМ ДИАБЕТИЧЕСКОЙ СТОПЫ

Goal of work - identify modifiable risk factors for chronic non-infectious diseases in patients with type 2 diabetes mellitus and in the formation of diabetic foot syndrome. Material and methods. A comparative medical and social study was conducted - a survey of patients in clinics of the city of Perm, suffering and not suffering from diabetes. The study involved 230 people who were assigned according to the presence/absence of diabetes mellitus. The first group included 178 patients with an average age of 45.8 (30.0; 59.0). The second group included 27 patients with diabetes mellitus, with an average age of 61.7 years (50.0; 62.0). The third group included 25 patients with diabetic foot syndrome, whose average age was 64.72 years (61.0; 69.0). Women predominated in all groups. Original and generally accepted questionnaires were used to study the presence of common risk factors for chronic diseases among respondents. Results. The analysis of the studied materials showed a clear qualitative and quantitative pattern of accumulation of risk factors in the age exponent. Most risk factors tend to grow up to 54-65 years. Risk factors such as smoking, alcohol abuse, poor nutrition and overweight, depression and hypertension predominate (р<0,05) in older age groups of respondents. In patients with diabetes mellitus, low physical activity, poor nutrition, and obesity predominate (р<0,05). In patients with diabetic foot syndrome, the same risk factors were identified as in patients without this pathology. At the same time, in respondents with diabetic foot syndrome, physical activity was minimal, and body mass index values were much higher (р<0,05); in addition, patients with diabetic foot syndrome are more likely (р<0,05) to be depressed and perceive their health as «very poor.»

Seroprevalence of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus among hemodialysis patients in a Tertiary Care Teaching Hospital in a developing country.

Background:Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) prevalence in hemodialysis patients varies geographically, both within and between countries. High prevalence of these infections in dialysis patients reflects the increased presence of common risk factors for their acquisition, including transfusion, transplantation, history of drug abuse, plus susceptibility to nosocomial transmission during dialysis.Objective:The aim of this study is to investigate the seroprevalence and clinical profile of HIV, HBV, and HCV patient's on hemodialysis.Materials and Methods:Clinical and epidemiological data of patients undergoing maintenance hemodialysis in the dialysis unit of a teaching institution were obtained and analyzed over a 5 years' period.Results:A total of 127 males and 69 females were studied. Their mean age was 50.45 years. Out of the total 196 dialysis-dependent patients, 2 (1.02%) were seropositive for HIV antibodies, 6 (3.06%) were hepatitis B surface antigen positive, and 30 (15.30%) were anti-HCV antibody positive. There was no coexistence of HIV, HBV, and HCV markers. The major primary renal diseases in hemodialysis patients included diabetes mellitus (42%), hypertension (22%), chronic nephritis (15%), urologic diseases (6%), cystic renal diseases (4%), and others (11%).Conclusion:Prevalence of transfusion-transmissible viral infections was higher among hemodialysis patients, especially HCV infection which was an alarming situation and therefore strict adherence to infection control strategies, barrier precautions, and preventive measures, including routine hepatitis B vaccination and regular virological follow-up were recommended along with regular education and training programs of technical and nursing personnel's involved with dialysis patients.

Estrogen, migraine, and vascular risk.

Migraine has a predilection for female sex and the course of symptoms is influenced by life stage (presence of menstrual cycle, pregnancy, puerperium, menopause) and use of hormone therapy, such as hormonal contraception and hormone replacement therapy. Hormonal changes figure among common migraine triggers, especially sudden estrogen drop. Moreover, estrogens can modulate neuronal excitability, through serotonin, norepinephrine, dopamine, and endorphin regulation, and they interact with the vascular endothelium of the brain. The risk of vascular disease, and ischemic stroke in particular, is increased in women with migraine with aura (MA), but the link is unclear. One hypothesis posits for a causal association: migraine may cause clinical or subclinical brain lesions following repeated episodes of cortical spreading depression (CSD) and a second hypothesis that may explain the association between migraine and vascular diseases is the presence of common risk factors and comorbidities. Estrogens can play a differential role depending on their action on healthy or damaged endothelium, their endogenous or exogenous origin, and the duration of their treatment. Moreover, platelet activity is increased in migraineurs women, and it is further stimulated by estrogens.This review article describes the course of migraine during various life stages, with a special focus on its hormonal pathogenesis and the associated risk of vascular diseases.

Relationship between serum total cholesterol level and serum biochemical bone turnover markers in healthy pre- and postmenopausal women.

Background. The presence of common risk factors suggests that there is a relationship between osteoporosis and cardiovascular disease, possibly via dyslipidemia and inflammation. We investigated the relationships among the lipid profile, the inflammation marker high-sensitivity C-reactive protein (hsCRP), bone turnover markers, and bone mineral density (BMD) to assess the correlation between osteoporosis and cardiovascular disease and identify factors predicting osteoporosis. Methods. The study included 759 Korean women older than 20 years of age. The BMD, serum lipid profile, and levels of hsCRP, cross-linked C-terminal peptide (CTX), and osteocalcin were measured. We compared the serum biomarkers between groups with normal and low BMD and assessed the correlations between the levels of bone turnover markers and the lipid profile and hsCRP level. Results. The concentrations of CTX, osteocalcin, and total cholesterol were significantly higher in the low BMD group than in the normal BMD group in premenopausal women group. However, hsCRP was not correlated with these parameters. Multivariate logistic regression analysis revealed that TC (OR, 1.647; 95% CI, 1.190–2.279) and osteocalcin (OR, 1.044; 95% CI, 1.002–1.088) had an increased risk of low BMD in premenopausal women. Conclusions. These results indicate that total cholesterol concentration is correlated with the levels of bone turnover markers, suggesting that it might predict osteoporosis in premenopausal women.

Epidemiology and management of coexisting heart failure and atrial fibrillation in an outpatient setting

Atrial fibrillation (AF) is the most common arrhythmia complicating heart failure (HF). The coexistence of these diseases may be partially explained by the presence of common risk factors. Although the effect of AF on the prognosis in HF is still debatable, it is associated with specific complications and affects therapy. The aim of this analysis was to evaluate epidemiology and management of coexisting HF and AF among Polish outpatients. The present study was performed within the framework of the Polish National Cardiovascular Disease Prevention and Treatment Program, POLKARD 2003-2005, and included patients with HF treated in a representative number of 400 outpatient clinics. Data was collected using questionnaires and included demographic characteristics as well as information about coexisting diseases and treatment, provided by patients and physicians on the basis of the available medical records. The study involved 3682 patients with HF (mean age 67.1 ±11.7 years; 58% of patients were men). AF was present in 38% of the patients. The prevalence of arrhythmia increased with the New York Heart Association class. We observed significant differences between the subgroups of patients with AF and those with sinus rhythm in terms of demographic parameters, risk factors, concomitant diseases, and therapy. Although the use of angiotensin-converting enzyme inhibitors and β-blockers was significantly lower in the subgroup with AF, a multivariable analysis showed that it was associated with specific demographic characteristics and comorbidities rather than with arrythmia itself. Specialty patient care was associated with increased use of therapy aimed to improve the prognosis of HF patients. Patients with AF constitute a particular subgroup within the population of patients with HF. A specific distribution of risk factors with a significant effect of noncardiac diseases may confound HF therapy in this patient group. Specialty care may be able to optimize treatment in patients with coexisting HF and AF.

Left Ventricular Diastolic Dysfunction in COPD May Manifest Myocardial Ischemia

Background: Left ventricular diastolic dysfunction (LVDD) is observed frequently in advanced COPD and it appears unrelated to the co-presence of its common risk factors as hypertension, diabetes, ischemic heart disease, etc. The patho-physiology of this association is yet unclear. We postulated that ischemia not apparent in the routine clinical evaluation could be the cause of such LVDD. Method: Advanced COPD (GOLD III & IV) patients being excluded of concomitant presence of hypertension, diabetes, ischemic heart disease, and hypothyroidism by conventional evaluations were looked for the presence of LVDD by tissue Doppler echocardiography. The subjects having LVDD were further evaluated with 99mTc MIBI stress myocardial perfusion imaging to detect the presence of ischemia. Results: 7out of 14 patients of advanced COPD sufferers without any known risk factors for LVDD had reversible perfusion defect in the stress perfusion imaging predominantly involving the inferior wall myocardium (71.43%). Most of the defects, though significant, were not picked up by stress ECG. Conclusion: Reversible ischemic defects are quite common (50%) in advanced COPD patients with LVDD without the presence of common risk factors. This association needs further evaluation.

Absence of cardiovascular disease risk factors in restless legs syndrome

Restless legs syndrome (RLS) might represent a condition at risk of cardiovascular (and cerebrovascular) disease; the role of sleep periodic leg movements, sleep deprivation, and presence of common risk factors for heart disease in these patients remains to be determined. The aim of this study was to evaluate the eventual presence of risk factors for cerebrovascular disease in RLS. Eighty-seven consecutive patients affected by idiopathic RLS were included in this study together with 81 controls. Blood count, chemistry, and kidney function tests were obtained. We detected subjects suffering from diabetes mellitus, kidney diseases, heart diseases, disk herniation, neuropathy, blood diseases, liver diseases, artery diseases, dyslipidemia, or hypertension. Polysomnography was recorded in 66 patients, and cerebral neuroimaging was obtained in 59 patients with RLS. None of the differences in blood test parameters was statistically significant; however, hypertension was found to be more frequent in controls and dyslipidemia was more frequent in patients with RLS, but this was explained by its higher frequency in patients also affected by obstructive sleep apnea. A diagnosis of cerebrovascular disease was posed for 14 patients with RLS (16.1%), but no predictive factor for its presence was found at the binomial logistic regression. Our findings argue against the presence of an altered lipid metabolism as a risk factor for the development of cerebrovascular disease in patients with RLS, even if they do support the idea that cerebrovascular disease might be frequent in this condition.

Lower urinary tract symptoms and erectile dysfunction: a role for PDE-5 inhibitors?

It is well established that lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are multifactorial and involve many pathophysiologic mechanisms. Until recently, the association between LUTS and ED has been attributed to the age link with a huge impact in the QoL at older ages. However, a large variety of large-scale epidemiological studies documented an age-independent relationship between LUTS and ED leading to a new research paradigm in search for the causal link. In fact, the MSAM-7 study (Multinational Survey of The Aging Male) revealed that erection problems (IIEF validated) were significantly more common in men with LUTS, and were strongly related to the severity of LUTS (IPSS validated), independently of the effects of age and other comorbidities. However, even if there is a link between LUTS and ED from an epidemiological perspective, the fact is that the causal relationship must be shown to have biological plausibility before acceptance is possible. Four pathophysiological mechanisms currently support this relationship: • The Nitric Oxide Synthase (NOS) / nitric oxide (NO) theory • Reduction in the NOS-containing nerves in the prostate, bladder and penis (in the presence of common risk factors for ED), suggests a possible increase in smooth muscle cell proliferation which may result in structural changes in the prostate and bladder leading to LUTS. • The autonomic hyperactivity and metabolic syndrome hypothesis • LUTS as a part of the metabolic syndrome which includes glucose intolerance, insulin resistance, obesity, dyslipidaemia and hypertension, all known risk factors for ED. These factors are associated with an increased sympathetic activity that can be involved in prostate growth, LUTS and DE with noradrenaline representing the common link. • The Rho-kinase activation/endothelin pathway • Increased Rho-kinase activity upregulates smooth muscle tone. Endothelin (a potent vasoconstrictor), is possibly involved in the increased smooth muscle activity found in both LUTS and ED and is dependent on Rhokinase activity that acts downstream from these receptors. • Pelvic atherosclerosis • Pelvic ischaemia can induce fibrosis, smooth muscle atrophy and non-compliance of the bladder. It also results in stromal fibrosis, glandular cystic atrophy and increases in smooth muscle contractility of the prostate, and penile fibrosis in the corpus cavernosum tissue. The increased production of TGF-s1 impairs neurogenic relaxation of the prostate and erectile tissue, involving a downregulation of the NO pathway. Recent studies suggest that PDE-5 inhibitors (PDE5-I) might have a beneficial effect on LUTS probably through the NO pathway. Under this treatment, both the International Prostatic Symptom Score (IPSS) and the International Index of Erectile Function (IIEF) improved from baseline. As NO and PDE5 enzymes have been identified in the human prostate, the improvement of both LUTS and ED might be mediated by an increased NO activity which leads to smooth muscle cell relaxation. Although placebo-controlled trials are needed to confirm the impact of these drugs on both LUTS and ED, the preliminary results reinforce the need for a common approach to managing these two highly prevalent and bothersome conditions.

Decreased Bone Mineral Density Is Correlated with Increased Subclinical Atherosclerosis in Older, but not Younger, Mexican American Women and Men: The San Antonio Family Osteoporosis Study

An association has been reported between cardiovascular disease (CVD) and osteoporosis, perhaps attributable to the presence of common risk factors. To assess this possibility, we measured areal bone mineral density (BMD) and carotid artery intimal medial thickness (IMT), a measure of preclinical atherosclerosis, in 535 women and 335 men from the San Antonio Family Osteoporosis Study. Variance decomposition methods were used to determine whether cross-sectional measures of areal BMD (measured by dual-energy X-ray absorptiometry) of the total hip, spine, and forearm were correlated with IMT, serum lipids, and/or C-reactive protein (CRP), a marker of inflammation, after accounting for known environmental factors. We observed significant inverse correlations of IMT and BMD at all bone sites in women >60 years of age (P < 0.001) and modest positive correlations (not significant) of IMT on hip BMD (P < 0.1) in women <60 years of age. Similarly, we observed negative correlations between IMT and forearm BMD in men >60 years of age (P < 0.001) and positive correlations in men <60 years of age (P = 0.05). Variation in risk factors for CVD, including serum levels of low- and high-density lipoprotein cholesterol, low-density lipoprotein particle size, triglycerides, paraoxonase 1 activity, and CRP did not account for the relationship between BMD and IMT in either older or younger men or women. In summary, our results demonstrate that decreased BMD is correlated with increased IMT in older (but not younger) Mexican American men and women, independent of serum CVD risk factors.

DE NOVO ANEURYSM FORMATION ON MIDDLE CEREBRAL ARTERY BRANCHES ADJACENT TO THE ANASTOMOTIC SITE OF SUPERFICIAL TEMPORAL ARTERY-MIDDLE CEREBRAL ARTERY BYPASS SURGERY IN TWO PATIENTS

Aneurysm formation is a complication of superficial temporal artery-middle cerebral artery bypass surgery occurring as pseudoaneurysms caused by technical failure, but also as true aneurysms discovered after long-term follow-up. A 53-year-old woman presented with a left internal carotid artery cavernous aneurysm manifesting as double vision. Superficial temporal artery-middle cerebral artery bypass, internal trapping of the internal carotid artery, and embolization were performed. Three years later, angiography disclosed a distal middle cerebral artery aneurysm. A 70-year-old man who had undergone right superficial temporal artery-middle cerebral artery bypass after internal carotid artery occlusion died of subarachnoid hemorrhage from a ruptured anterior spinal artery aneurysm 21 years later. Angiography and postmortem examination revealed de novo aneurysm formation on a middle cerebral artery branch adjoining the anastomotic site. Both patients had hypertension and multiplicity of aneurysms. Both cases were de novo true aneurysms caused by hemodynamic stress because of saccular to fusiform shape, location extending to the middle cerebral artery, high perfusion pressure, projection along the hemodynamic stress, and presence of common risk factors. Bypass surgery is increasingly performed in patients with complicated aneurysms if sacrifice or temporary occlusion of any major vessel is required. Therefore, de novo aneurysm formation may not be rare in patients with risk factors such as hypertension or multiple aneurysms. Extended follow-up examination is required in such patients.

Genetic Causes of Stroke and Vascular Dementia

Ischemic and hemorrhagic stroke are probably multifactorial diseases. A combination of environmental and genetic risk factors are likely to play a role. The genetic contribution is complex (polygenic; multiple genes), as the presence of common risk factors for stroke, such as diabetes and hypertension, is partly determined by genetic predisposition. All types of stroke (e.g., cortical, subcortical, lacunar and hemorrhagic) can lead to vascular dementia. Consequently, vascular dementia can also be considered to be a complex genetic disease. However, genetic studies on vascular dementia are scarce. Recent studies have focused on monogenic forms of stroke, such as cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy and the amyloid angiopathies. These disorders can probably serve as models to study factors that may also contribute to the common forms of stroke and vascular dementia.