Pre-pregnancy risk assessment and counselling of the cardiac patient

Pregnant women with heart disease often have an increased risk of maternal cardiovascular and offspring complications. The magnitude of these risks varies depending on the type and severity of the underlying disease. Therefore risk assessment should be performed before pregnancy. This can be accomplished by taking into account predictors and risk scores that have been developed in large populations of pregnant women with heart disease, as well as by consulting disease-specific pregnancy literature. A system that integrates all available knowledge about the risk of pregnancy is the adapted World Health Organisation risk classification. The safety of pregnancy for women with heart disease can be enhanced by adequate risk assessment and counselling.     

Change in alcohol consumption and risk of death from all causes and from ischaemic heart disease.

OBJECTIVE--To examine the association between alcohol consumption and mortality from all causes and from ischaemic heart disease with a focus on differentiating between long term abstainers and more recent non-drinkers. DESIGN--Cohort study of changes in alcohol consumption from 1965 to 1974 and mortality from all causes and ischaemic heart disease during 1974-84. SETTING--Population based study of adult residents of Alameda County, California. SUBJECTS--2225 women and 1845 men aged 35 and over in 1965. MAIN OUTCOME MEASURES--Alcohol consumption in 1964 and 1974 and mortality from all causes and from ischaemic heart disease during 1974-84. RESULTS--There was a significantly higher risk of death from all causes and from ischaemic heart disease in women who gave up drinking between 1965 and 1974 than in women who continued to drink (relative risk 1.72, 95% confidence interval 1.11 to 2.66, and 2.75, 1.44 to 5.23, for all causes and ischaemic heart disease respectively). A significant increase in risk was not seen in men who gave up drinking (1.32, 0.87 to 2.01, and 0.95, 0.41 to 2.20, respectively). Among men, long term abstainers compared with drinkers were at increased risk of death from all causes and from ischaemic heart disease, though the associations were not significant (1.40, 0.98 to 2.00, and 1.40, 0.76 to 2.58, for all causes and ischaemic heart disease respectively). CONCLUSION--Some of the increased risk of death from all causes and from ischaemic heart disease associated with not drinking in women seems to be accounted for by higher risks among those who gave up drinking. Men who are long term abstainers may also be at an increased risk of death. The heterogeneity of the non-drinking group should be considered when comparisons are made with drinkers.     

Dental disease and risk of coronary heart disease and mortality.

OBJECTIVE--To investigate a reported association between dental disease and risk of coronary heart disease. SETTING--National sample of American adults who participated in a health examination survey in the early 1970s. DESIGN--Prospective cohort study in which participants underwent a standard dental examination at baseline and were followed up to 1987. Proportional hazards analysis was used to estimate relative risks adjusted for several covariates. MAIN OUTCOME MEASURES--Incidence of mortality or admission to hospital because of coronary heart disease; total mortality. RESULTS--Among all 9760 subjects included in the analysis those with periodontitis had a 25% increased risk of coronary heart disease relative to those with minimal periodontal disease. Poor oral hygiene, determined by the extent of dental debris and calculus, was also associated with an increased incidence of coronary heart disease. In men younger than 50 years at baseline periodontal disease was a stronger risk factor for coronary heart disease; men with periodontitis had a relative risk of 1.72. Both periodontal disease and poor oral hygiene showed stronger associations with total mortality than with coronary heart disease. CONCLUSION--Dental disease is associated with an increased risk of coronary heart disease, particularly in young men. Whether this is a causal association is unclear. Dental health may be a more general indicator of personal hygiene and possibly health care practices.     

A woman's heart. An update of coronary artery disease risk in women.

Coronary artery disease accounts for a third of all deaths in women. Traditionally, studies on this disease have been conducted with male subjects. A growing body of evidence indicates that oral contraceptive and postmenopausal estrogen use present risk factors for the disease that are unique to women. In addition, sex differences exist with regard to the relationship of most of these risk factors to the development of the disease. An understanding of these differences has an important role in expanding the management of coronary artery disease risk reduction for women and in defining directions for future research.     

C-reactive protein as a risk factor versus risk marker

PURPOSE OF REVIEW: C-reactive protein (CRP) is consistently associated with cardiovascular disease in prospective and cross-sectional clinical and epidemiological studies. Inflammation is an important mechanism in cardiovascular disease, and the plasma level of CRP is considered to reflect the inflammatory condition of the patient and/or the vessel wall. In addition, there are also a number of indications for a causal role of CRP in cardiovascular disease. RECENT FINDINGS: A number of new publications show potential causal effects of CRP on cardiovascular disease, and evidence from human-CRP transgenic animals also indicates a causal contribution of CRP to cardiovascular disease. On the other hand, a new large prospective study and an updated meta-analysis indicate that the contribution of CRP to cardiovascular disease is less impressive than reported earlier (odds ratio, 1.58; 95% confidence interval, 1.48-1.68). SUMMARY: We review here the most recent evidence on mechanisms by which CRP is involved as a causal factor in the precipitation of cardiovascular disease. Evidence for such a role is accumulating.     

Intermittent claudication: prevalence and risk factors.

Risk factors for intermittent claudication (IC) were studied in 54 patients--that is, all patients with IC on the lists of two general practices--and 108 controls. Smoking was the factor most strongly associated with the development of IC, but systolic and diastolic blood pressures and concentrations of triglyceride, urate, and fibrinogen were all significantly higher among the patients with IC than the controls. The presence of more than one factor appeared to be associated with a multiplicative increase in risk. Cholesterol, an important risk factor for ischaemic heart disease, was not associated with an increased risk of IC. IC was present in about 2% of the men and 1% of the women, who were aged 45-69 years. These findings suggest that IC, a common and disabling manifestation of atheroslcerosis, may be largely preventable.     

Evidence that disgust evolved to protect from risk of disease

Disgust is a powerful human emotion that has been little studied until recently. Current theories do not coherently explain the purpose of disgust, nor why a wide range of stimuli can provoke a similar emotional response. Over 40 000 individuals completed a web-based survey using photo stimuli. Images of objects holding a potential disease threat were reported as significantly more disgusting than similar images with little or no disease relevance. This pattern of response was found across all regions of the world. Females reported higher disgust sensitivity than males; there was a constant decline in disgust sensitivity over the life course; and the bodily fluids of strangers were found more disgusting than those of close relatives. These data provide evidence that the human disgust emotion may be an evolved response to objects in the environment that represent threats of infectious disease.     

Ecological factors influencing disease risk in Eagle Owls Bubo bubo

In this study we assessed whether local habitat features and host population density influenced disease risk in Eagle Owl Bubo bubo fledglings. Measures of immune defence (concentrations of circulating white blood cells), prevalence of three parasite types (a blood parasite Leucocytozoon ziemanni , an insect Carnus haemapterus , and a tick Rhipicephalus sp.) and total number of parasite species were used to quantify disease risk. We tested the hypotheses that disease risk in fledglings was higher in nests located in areas with higher length of and proximity to watercourses (as a higher abundance and viability of parasites and vectors occur in wetter areas), higher cover of forest (as forest moistness and humidity can favour higher vector and parasite proliferation), higher habitat diversity (as environmental heterogeneity increases the pool of potential vectors and parasites) and higher local owl population density (as disease transmission might be density-dependent). The clearest relationship was with the proximity of freshwater, although the other hypotheses were also partially supported. Concentrations of white blood cells, the number of parasite species and, weakly, the prevalence of Carnus haemapterus were all higher in nests closer to watercourses. The prevalence of blood parasites increased with the cover of forested areas. Fledglings from nests located in more diverse habitats had higher white blood cell concentrations and showed higher prevalence of blood parasites. Finally, local host population density was positively correlated with the prevalence of blood parasites. The results suggest the existence of complex and interrelated links between ecological parameters and three different measures of disease risk, and highlight the importance of immunological approaches to assess disease risk at an intraspecific level.     

Cardiovascular risk in women after metabolic complications in pregnancy

Hypertensive pregnancy disorders complicate 10% of all pregnancies. In this article we discuss the spectrum of hypertensive conditions that may occur during pregnancy. Recent studies have consistently shown that hypertensive disorders in pregnancy implicate a two-fold higher risk for the development of hypertension and cardiovascular disease later in life. To optimise preventive management of cardiovascular disease in women with previous complicated pregnancies, we therefore recommend monitoring of hypertension and other cardiac risk factors at an early stage in life. Furthermore, the obstetric history should be routinely incorporated in cardiovascular risk assessment in women who seek medical attention for hypertension and/or cardiac symptoms. (Neth Heart J 2007;15:415-7.)     

Forest species diversity reduces disease risk in a generalist plant pathogen invasion

Empirical evidence suggests that biodiversity loss can increase disease transmission, yet our understanding of the 'diversity-disease hypothesis' for generalist pathogens in natural ecosystems is limited. We used a landscape epidemiological approach to examine two scenarios regarding diversity effects on the emerging plant pathogen Phytophthora ramorum across a broad, heterogeneous ecoregion: (1) an amplification effect exists where disease risk is greater in areas with higher plant diversity due to the pathogen's wide host range, or (2) a dilution effect where risk is reduced with increasing diversity due to lower competency of alternative hosts. We found evidence for pathogen dilution, whereby disease risk was lower in sites with higher species diversity, after accounting for potentially confounding effects of host density and landscape heterogeneity. Our results suggest that although nearly all plants in the ecosystem are hosts, alternative hosts may dilute disease transmission by competent hosts, thereby buffering forest health from infectious disease.     

Glycated hemoglobin as a marker of cardiovascular risk

PURPOSE OF REVIEW: Diabetes mellitus is an established risk factor for cardiovascular disease. This review examines glycated hemoglobin, an indicator of long-term average blood glucose concentrations, in risk prediction for cardiovascular disease. RECENT FINDINGS: Glycated hemoglobin concentrations predict cardiovascular disease risk in people with diabetes, and trial data suggest that good blood glucose control is associated with reduction in cardiovascular disease. Elevated glycated hemoglobin levels below the thresholds accepted for diabetes are also associated with increasing cardiovascular disease risk independent of classical risk factors in a continuous relationship across the whole normal distribution. A 1% increase in absolute concentrations of glycated hemoglobin is associated with about 10-20% increase in cardiovascular disease risk. The continuous relationship is most evident for coronary heart disease in men; the shape of the risk curve is less clear for women and for other cardiovascular endpoints such as stroke or peripheral vascular disease. SUMMARY: Glycated hemoglobin concentration predicts cardiovascular risk both in people with diabetes and in the general population, and may help identify individuals at higher risk of cardiovascular disease for targeted interventions, including blood pressure or cholesterol reduction. Understanding the nature of this relationship may inform new preventive and therapeutic interventions.     

Accuracy of predicting the genetic risk of disease using a genome-wide approach

Background

The prediction of the genetic disease risk of an individual is a powerful public health tool. While predicting risk has been successful in diseases which follow simple Mendelian inheritance, it has proven challenging in complex diseases for which a large number of loci contribute to the genetic variance. The large numbers of single nucleotide polymorphisms now available provide new opportunities for predicting genetic risk of complex diseases with high accuracy.

Methodology/Principal Findings

We have derived simple deterministic formulae to predict the accuracy of predicted genetic risk from population or case control studies using a genome-wide approach and assuming a dichotomous disease phenotype with an underlying continuous liability. We show that the prediction equations are special cases of the more general problem of predicting the accuracy of estimates of genetic values of a continuous phenotype. Our predictive equations are responsive to all parameters that affect accuracy and they are independent of allele frequency and effect distributions. Deterministic prediction errors when tested by simulation were generally small. The common link among the expressions for accuracy is that they are best summarized as the product of the ratio of number of phenotypic records per number of risk loci and the observed heritability.

Conclusions/Significance

This study advances the understanding of the relative power of case control and population studies of disease. The predictions represent an upper bound of accuracy which may be achievable with improved effect estimation methods. The formulae derived will help researchers determine an appropriate sample size to attain a certain accuracy when predicting genetic risk.     

Serum triglycerides and risk of cardiovascular disease

Dyslipidemia, especially elevated serum levels of cholesterol, is causally related to cardiovascular disease. The specific role of triglycerides has long been controversial. In this article we discuss the role of serum triglycerides in relation to the risk of cardiovascular disease. First, the (patho)physiology of triglycerides is described, including the definition and a short summary of the primary and secondary causes of hypertriglyceridemia. Furthermore, we will give an overview of the published epidemiological studies concerning hypertriglyceridemia and cardiovascular disease to support the view that triglyceride-rich lipoproteins are an independently associated risk factor. Finally, treatment strategies and treatment targets are discussed. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.     

A simplified Finnish diabetes risk score to predict type 2 diabetes risk and disease evolution in a German population.

AIMS: The FINDRISC questionnaire is a screening tool to estimate the risks for type 2 diabetes as well as asymptomatic type 2 diabetes. We aimed to evaluate its performance to predict diabetes in a German population and to compare its predictive and detective ability in the same population. METHODS: A total of 552 subjects with increased risk of type 2 diabetes were investigated. All individuals completed the FINDRISC questionnaires and underwent an oral glucose tolerance test (OGTT). All individuals were followed for 3 years and underwent an OGTT again. The performance of the opportunistic screening was assessed with the area under the receiver operating characteristics curve (AUC). An intervention program was carried out for all diabetic and IFG/IGT patients at baseline. RESULTS: For identification, the asymptomatic type 2 DM was named Condition 1; prediction of type 2 DM risk in the follow-up survey as Condition 2; and diabetes risk predicting in a hypothetical case of survey without intervention program as Condition 3. The ROC-AUC in the three condition were AUC (FINDRISC1)=0.745, AUC (FINDRISC2)=0.789, and AUC (FINDRISC3)=0.775, respectively. A significant association between FINDRISC and evolution of disease was found, but the variation of plasma glucose during the three years follow-up was not associated with FINDRISC. People in the intervention group with an improvement of glucose tolerance had a smaller FINDRISC score than persons with an unchanged or progressive condition of disease. CONCLUSION: FINDRISC was validated in our study as a simple tool with high performance to predict diabetes risk and less efficient to identify asymptomatic type 2 diabetes. People with lower FINDRISC score will benefit easier from preventive intervention.     

Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk

Background

Macrovascular diseases (MVD) in type 2 diabetes mellitus (T2DM) are often considered all together, without discriminating the areas involved. The aim of our study was to analyse MVD prevalence in a large population of T2DM patients by dividing the cases into subgroups according to MVD sites (NMVD, no MVD; NSCS, non-significant carotid stenosis; CBVD, cerebrovascular disease; CAD, coronary artery disease; PAD, peripheral artery disease; PVD, polyvascular disease) and studying the anthropometric, clinical and laboratory parameters in each group.

Methods

A diabetic outpatient cohort (n = 1199) was retrospectively studied. Demographic, clinical and laboratory parameters were included in analyses. A thorough cardiovascular history as documented by previous medical records (including medical and hospital records) and vascular laboratory studies (including standardised electrocardiogram, echocardiogram, provocative tests for cardiac ischaemia, ankle/brachial index, duplex ultrasonography of the carotid and lower limbs and, in selected cases, computed tomography angiography, carotid and peripheral arteriography and evaluation of transcutaneous oxygen pressure), was collected for all of the patients. Standardised procedures were used to assess microvascular complications as well as metabolic syndrome (Mets).

Results

The unadjusted MVD prevalence was 46.4% among the participants. The majority of patients with MVD were in the PVD group. In the multivariate analysis, age, male sex and diabetes duration were independent risk factors for PAD and PVD (P < 0.01). A low HDL-C value was an independent risk factor in the CAD and PVD groups (P = 0.03). Very high frequencies of MetS were observed in the PAD and PVD groups (94.9 and 95.7% respectively). The most MetS diagnostic criteria were recorded among members of the CAD group (all or all-1 criteria were present in 73% of patients). The average age in the CAD group (64.5 y) was comparable to that of the NMVD group. Microvascular complications were more frequent in the PAD and PVD patients.

Conclusion

Phenotypic heterogeneity is associated with different macrovascular complications in T2DM patients. These findings might have clinical implications for developing diagnostic and therapeutic strategies targeting type 2 diabetes.     

Growth hormone treatment: cancer risk

There have been concerns that growth hormone (GH) therapy may be associated with an increased risk of cancer. Although data are limited and conflicting, one recent report on cancer risk in individuals with no cancer history or risk factors for cancer who were treated with pituitary GH demonstrated a small increased risk of colon cancer and deaths from colon cancer and Hodgkin disease. The data from cancer survivors have consistently shown no increased risk of recurrence of the primary tumor in survivors of all tumor types who are treated with GH. One recent study did show a small increased risk of second solid tumors in survivors previously treated with GH. Limited data suggest that GH therapy is not associated with excess cancer risk in individuals with Langerhans cell histiocytosis and neurofibromatosis type 1. Overall, the clinical data are reassuring, but continued surveillance is mandatory.     

Melanoma risk factors and atypical moles.

Despite important advances in the treatment of melanoma, the prognosis for advanced disease remains discouraging. This fact, in combination with a worldwide epidemic of melanoma among persons of white skin type, has focused attention on identifying melanoma in its early, surgically curable stages. Attention has also been directed toward pinpointing which persons are at increased risk for melanoma to reduce risk where possible and to aid early diagnosis. Essentially all epidemiologic studies have identified an increased number of melanocytic nevi as an important risk factor in the development of melanoma, but controversy has arisen concerning the risk associated with certain types of nevi, particularly "dysplastic" nevi. We review melanoma risk factors and examine the relationship between melanocytic nevi and melanoma to clarify for primary care physicians what is "known" (non-controversial) and what is "unknown" (controversial). We propose a working definition of an atypical mole phenotype and outline an approach to managing high-risk patients.     

Inflammatory cytokines and malnutrition as related to risk for cardiovascular disease in hemodialysis patients

Malnutrition and inflammation are associated with end-stage renal disease (ESRD). Interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) powerfully predict death from cardiovascular disease. The aim of our study was to establish an association between markers of inflammation and parameters of malnutrition in patients on hemodialysis. The study population consisted of 42 hemodialysis patients with different parameters of malnutrition. Blood samples were taken after an overnight fast, and plasma lipid profiles (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) were measured by using conventional enzymatic methods. Serum urea and creatinine levels were also measured by routine procedures. Plasma high-sensitivity C-reactive protein level (hs-CRP), TNF-alpha, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Standard Doppler echo examinations were used to determine plaque on carotid arteries, and end-diastolic diameter (EDD) and ejection fraction (EF) were measured by echocardiography. Malnourished patients exhibited significantly greater evidence of cardiovascular disease and carotid plaques. Factor (principal component) analysis indicated 6 latent factors with 67.5% of the variance explained within all investigated parameters. Cluster analysis was used to distinguish the inflammatory markers and the nutritional markers from other parameters and to visualize similarities between variables. In summary, this cross-sectional study in hemodialysis patients found a high prevalence of malnutrition, inflammation, carotid plaques, and cardiovascular disease. Malnourished dialysis patients are more often found with cardiovascular disease and carotid plaques. In addition, these patients have higher levels of inflammatory cytokines, which may partly explain the elevated risk for atherosclerotic vascular disease.     

Predicting impacts of climate change on Fasciola hepatica risk

Fasciola hepatica (liver fluke) is a physically and economically devastating parasitic trematode whose rise in recent years has been attributed to climate change. Climate has an impact on the free-living stages of the parasite and its intermediate host Lymnaea truncatula, with the interactions between rainfall and temperature having the greatest influence on transmission efficacy. There have been a number of short term climate driven forecasts developed to predict the following season's infection risk, with the Ollerenshaw index being the most widely used. Through the synthesis of a modified Ollerenshaw index with the UKCP09 fine scale climate projection data we have developed long term seasonal risk forecasts up to 2070 at a 25 km square resolution. Additionally UKCIP gridded datasets at 5 km square resolution from 1970-2006 were used to highlight the climate-driven increase to date. The maps show unprecedented levels of future fasciolosis risk in parts of the UK, with risk of serious epidemics in Wales by 2050. The seasonal risk maps demonstrate the possible change in the timing of disease outbreaks due to increased risk from overwintering larvae. Despite an overall long term increase in all regions of the UK, spatio-temporal variation in risk levels is expected. Infection risk will reduce in some areas and fluctuate greatly in others with a predicted decrease in summer infection for parts of the UK due to restricted water availability. This forecast is the first approximation of the potential impacts of climate change on fasciolosis risk in the UK. It can be used as a basis for indicating where active disease surveillance should be targeted and where the development of improved mitigation or adaptation measures is likely to bring the greatest benefits.     

Prostate cancer risk in testosterone-treated men

Men with classical androgen deficiency have reduced prostate volume and blood prostate-specific antigen (PSA) levels compared with their age peers. As it is plausible that androgen deficiency partially protects against prostate disease, and that restoring androgen exposure increases risk to that of eugonadal men of the same age, men using ART should have age-appropriate surveillance for prostate disease. This should comprise rectal examination and blood PSA measurement at regular intervals (determined by age and family history) according to the recommendations, permanently revisited, published by ISSAM, EAU, Endocrine Society….

Testosterone replacement therapy is now being prescribed more often for aging men, the same population in which prostate cancer incidence increases; it has been suggested that administration in men with unrecognised prostate cancer might promote the development of clinically significant disease. In hypogonadal men who were candidates for testosterone therapy, a 14% incidence of occult cancer was found. A percentage (15.2%) of prostate cancer has been found in the placebo group (with normal DRE and PSA) in the prostate cancer prevention study investigating the chemoprevention potential of finasteride.

The hypothesis that high levels of circulating androgens is a risk factor for prostate cancer is supported by the dramatic regression, after castration, of tumour symptoms in men with advanced prostate cancer. However these effects, seen at a very late stage of cancer development, may not be relevant to reflect the effects of variations within a physiological range at an earlier stage.

Data from all published prospective studies on circulating level of total and free testosterone do not support the hypothesis that high levels of circulating androgens are associated with an increased risk of prostate cancer. A study on a large prospective cohort of 10,049 men, contributes to the gathering evidence that the long standing “androgen hypothesis” of increasing risk with increasing androgen levels can be rejected, suggesting instead that high levels within the reference range of androgens, estrogens and adrenal androgens decrease aggressive prostate cancer risk. Indeed, high-grade prostate cancer has been associated with low plasma level of testosterone. Furthermore, pre-treatment total testosterone was an independent predictor of extraprostatic disease in patients with localized prostate cancer; as testosterone decreases, patients have an increased likelihood of non-organ confined disease and low serum testosterone levels are associated with positive surgical margins in radical retropubic prostatectomy.

A clinical implication of these results concerns androgen supplementation which has become easier to administer with the advent of transdermal preparations (patch or gel) that achieve physiological testosterone serum levels without supra physiological escape levels. During the clinical development of a new testosterone patch in more than 200 primary or secondary hypogonadal patients, no prostate cancer was diagnosed.