Burden of Cardiometabolic Risk Factors on Cerebrovascular Events in a Southern Italian Population

Cardio-cerebrovascular (CCV) disease contributes significantly to the global burden of disease, with dramatic consequences in terms of mortality and general health. Mitigate CCV risk factors is the key to reduce individual and population risk of CCV events. Evidence-based medicine and epidemiological investigations of risk factors are essential to optimize actions. To contribute to the knowledge of the burden of risk factors in determining CCV events in the individual patient and in the community. Clinical data and risk factors were collected through a longitudinal survey (1999) as part of a larger epidemiology and cardiovascular prevention project, namely the "VIP (Valle dell'Irno Prevention) Project". We assessed the incidence of major cardiovascular events (MACE) and for each risk factor we calculated: prevalence, absolute risk, odds ratio (OR), additional risk (AR) = risk of exposed to the risk factor - risk of non-exposed, population attributable risk (PAR) = additional risk * prevalence, population attributable risk fraction (PAF) = PAR/total incidence of the disease. Comparing the MACE group with the non-MACE group, a statistically significant difference was found for the following: glomerular filtration rate (GFR), glucose and systolic blood pressure (SBP), BMI, diastolic blood pressure (DBP), cholesterol, triglycerides, creatinine and uric acid. GFR, glucose and SBP showed the highest OR. Age, creatinine, glycemia, SBP and uric acid were independent predictor of MACE. When calculating the PAF, the CCV risk factors with the greatest impact on MACE were: SBP (29.6%), triglyceridemia (19.4%) and metabolic syndrome (18.3%). The burden of risk factors on MACE changes substantially according to whether it is calculated in the single patient or in the population. It is crucial for physicians to take these differences into account when applying their own intervention to reduce CCV events.

To evaluate the burden and association of cardiometabolic risk factors in the spouses of women with and without hyperglycaemia in pregnancy. Women with (n=204) and without (n=197) hyperglycaemia in pregnancy, along with their spouses, participated in this cross-sectional study. The hyperglycaemia in pregnancy group included women with gestational diabetes and diabetes in pregnancy. A detailed questionnaire was completed for all participants (men and women), documenting relevant personal and medical history, along with biochemical investigations (men). A total of 401 couples were evaluated at the time point during the pregnancy of 24.7±5.2 gestational weeks (mean ± sd). Dysglycaemia (prediabetes or diabetes), overweight/obesity (BMI ≥25 kg/m2 ) and metabolic syndrome were detected in 120 (58.9%), 123 (60.3%) and 98 spouses (48.3%) of women with hyperglycaemia in pregnancy, respectively. In the fully adjusted model, an increased risk of dysglycaemia [odds ratio 1.43 (95% CI 0.95-2.17); P=0.088], overweight/obesity [odds ratio 1.49 (95% CI 0.98-2.27); P=0.064] and metabolic syndrome [odds ratio 2.00 (95% CI 1.30-3.07); P=0.001] was seen in the spouses of women with hyperglycaemia in pregnancy. The prevalence of these metabolic conditions was higher in spouses of women with diabetes in pregnancy compared to spouses of women with gestational diabetes mellitus. A high burden of cardiometabolic risk factors was observed in the spouses of women with hyperglycaemia in pregnancy. The opportunity provided by pregnancy could be used by the healthcare system not only to improve the health of the woman and her offspring, but also her spouse.

This report was derived from a workshop on cardiovascular risk assessment sponsored by the National Heart, Lung, and Blood Institute, which addressed whether risk equations developed in the Framingham Heart Study (FHS) for predicting new-onset coronary heart disease (CHD) apply to diverse population groups. Preparation for the workshop included a reanalysis and comparison of prospective studies in several different populations in which risk factors were related to cardiovascular outcomes. Some studies included fatal and nonfatal CHD end points, whereas others contained only CHD mortality. Extensive collaboration provided as much uniformity as possible with respect to both risk factors and CHD end points. The FHS has led in defining the quantitative impact of risk factors.1 Many potential risk factors were measured and related to cardiovascular outcomes. Several risk factors proved to be strong, largely independent predictors of cardiovascular disease (CVD). These factors—advancing age, cigarette smoking, blood pressure (particularly systolic), cholesterol in total serum and HDL, and diabetes—served as the basis for the development of risk prediction equations.1 If FHS risk estimates are to be widely used, they must apply widely in the US population. To document their transportability, they must be compared with prospective studies in other populations. Although the FHS is the longest running prospective study, there are other major studies. The cardiovascular end points of these other studies have varied. Some include cardiovascular morbidity and mortality; others have only cardiovascular mortality. Among the end points, CHD is the most extensively reported; for this reason, CHD was the primary focus of the workshop. ### Multivariate Relative Risk Comparisons In preparation for the workshop, multivariate regression coefficients for each risk factor were compared in different populations with those of the FHS. Adjusted relative risk estimates make it possible to determine whether each independent risk factor confers a similar or different relative risk among different …

Stroke ranks as the third leading cause of death in the United States. It is now estimated that there are more than 700 000 incident strokes annually and 4.4 million stroke survivors.1 2 The economic burden of stroke was estimated by the American Heart Association to be $51 billion (direct and indirect costs) in 1999.3 Despite the advent of treatment of selected patients with acute ischemic stroke with tissue plasminogen activator and the promise of other experimental therapies, the best approach to reducing the burden of stroke remains prevention.4 5 High-risk or stroke-prone individuals can be identified and targeted for specific interventions.6 This is important because epidemiological data suggest a substantial leveling off of prior declines in stroke-related mortality and a possible increase in stroke incidence.7 8 The Stroke Council of the American Heart Association formed an ad hoc writing group to provide a clear and concise overview of the evidence regarding various established and potential stroke risk factors. The writing group was chosen based on expertise in specific subject areas, and it used literature review, reference to previously published guidelines, and expert opinion to summarize existing evidence and formulate recommendations (Table 1⇓). View this table: Table 1. Levels of Evidence and Grading of Recommendations As given in Tables 2 through 4⇓⇓⇓, risk factors or risk markers for a first stroke were classified according to potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented, less well documented).5 The tables give the estimated prevalence, population attributable risk, relative risk, and risk reduction with treatment for each factor when known. Population attributable risk reflects the proportion of ischemic strokes in the population that can be attributed to a particular risk factor and is given by the formula 100×[prevalence(relative risk−1)/prevalence(relative risk−1)+1]). …

Oral microflora associated with periodontal disease (PD) has been proposed to be a causal factor for cardiovascular disease (CVD).Data from NHANES I and its 21-year follow-up were used to test this hypothesis.Baseline periodontal status was categorized into (1)no PD, (2)gingivitis, (3)periodontitis, and (4) edentulousness.CVD events during follow-up were ascertained by hospital records for non-fatal events and death certificates for fatal events.Relative risk (RR) and 95% confidence interval (CI) were derived from Cox regression after adjusting for demographic variables and several well-established CVD risk factors.9,962 people were free from coronary heart disease (CHD), heart failure, and cancer at baseline.2,844 CVD, 1,468 CHD, and 803 stroke events occurred during the follow-up.Compared to no PD, RRs (CI) of CVD were 1.05 (0.93-1.18) for gingivitis, 1.17 (1.04-1.31)for periodontitis, and 1.22 (1.10-1.34)for edentulousness.RRs (CI) at similar PD levels for CHD were 1.03 (0.87-1.21), 1.14 (0.98-1.34), and 1.13 (0.98-1.32), and for stroke were 1.03 (0.81-1.31), 1.33 (1.07-1.66),and 1.30 (1.06-1.60),respectively.Analyses stratified by age group indicated that elevated risk for CVD associated with PD is manifested mainly in those aged 25-54 years at baseline.Among this age group, RRs (CI) of CVD were 1.13 (0.96-1.33) for gingivitis, 1.40 (1.16-1.68)for periodontitis, and 1.36 (1.11-1.68)for edentulousness in comparison to no PD; RRs (CI) of CHD were 1.13 (0.80-1.29), 1.33 (1.03-1.72),and 1.25 (0.93-1.67); and RRs (CI) of stroke were 0.96 (0.64-1.46), 1.57 (1.05-2.36),and 1.46 (0.92-2.33), respectively.This study suggests that periodontal disease is a significant risk factor for CVD, CHD, and stroke especially in adults aged 25-54. P2 Stress in the workplace and early atherosclerosis. The Los Angeles

The Framingham Heart Study has contributed importantly to understanding of the causes of coronary heart disease (CHD), stroke, and other cardiovascular diseases. Framingham research has helped define the quantitative and additive nature of these causes or, as they are now called, “cardiovascular risk factors.”1 The National Cholesterol Education Program (NCEP)2 3 has made extensive use of Framingham data in developing its strategy for preventing CHD by controlling high cholesterol levels. The NCEP guidelines2 3 adjust the intensity of cholesterol-lowering therapy with absolute risk as determined by summation of risk factors. The National High Blood Pressure Education Program (NHBPEP) has set forth a parallel approach for blood pressure control. In contrast to the NCEP,2 however, earlier NHBPEP reports issued through the Joint National Committee4 did not match the intensity of therapy to absolute risk for CHD. “Normalization” of blood pressure is the essential goal of therapy regardless of risk status. Blood pressure–lowering therapy is carried out as much for prevention of stroke and other cardiovascular complications as for reduction of CHD risk. Nonetheless, risk assessment could be important for making decisions about type and intensity of therapy for hypertension. Thus, the most recent Joint National Committee report5 gives more attention to risk stratification for adjustment of therapy for hypertension. Although Framingham data have already been influential in the development of national guidelines for risk factor management, the opportunity may exist for both cholesterol and blood pressure programs to draw more extensively from Framingham results when formulating improved risk assessment guidelines and recommending more specific strategies for risk factor modification. The American Heart Association has previously used Framingham risk factor data to prepare charts for estimating CHD risk. Framingham investigators of the National Heart, Lung, and Blood Institute prepared the original charts and have now revised …

Establishing new approaches for the prevention and treatment of stroke relies on identifying modifiable risk factors that contribute to the development of this complex disease. Mendelian randomization (MR) studies, analogous to naturally occurring randomized trials, can assess causality of potentially modifiable biomarkers and offer new insights into biological pathways. Stroke is the second leading cause of death worldwide and the chief determinant of long-term disability. Stroke is a heterogeneous disease arising from several distinct underlying pathologies and is typically classified as ischemic or hemorrhagic, and further subclassified using imaging data. Ischemic stroke (IS), including its 3 main subtypes: small vessel disease, large vessel disease, and cardioembolic stroke, accounts for ≈80% of stroke and is the result of an interrupted blood supply, leading to localized areas of ischemia in the brain. Small vessel disease may be a consequence of nonatherosclerotic, as well as atherosclerotic, mechanisms that result in an occlusion of the small perforating arteries, whereas large vessel disease results from occlusions or emboli from plaque rupture in larger vessels, such as a carotid artery. Cardioembolic stroke arises typically from emboli from the heart. By contrast, hemorrhagic stroke is a consequence of intracerebral hemorrhage (bleeding into the brain) or subarachnoid hemorrhage (bleeding into the subarachnoid space). These diverse stroke subtypes have distinct underlying pathologies reflecting different risk factor distributions. MR studies, using genetic variants as instrumental variables, afford a powerful approach to assessing causality of risk factors and avoid biases inherent in observational studies, including confounding and reverse causation. This review considers the contribution of MR studies to stroke epidemiology and their relevance to understanding risk factors and new therapeutic targets for stroke. Meta-analyses of large prospective studies have enhanced our knowledge of classical and emerging risk factors for stroke.1–4 Classical risk factors for stroke include nonmodifiable characteristics, …

The International Stroke Conference 2008 New Orleans, Louisiana February 20-22, 2008

The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension-related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence interval, -7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% confidence interval, 0.6-15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% confidence interval, 0.1-0.8; P=0.02), but not midodrine (means difference=0.5; 95% confidence interval, -0.1 to 1.0; P=0.08), improved orthostatic hypotension-related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure.

To determine the clinical and anatomical risk factors for cerebrovascular accidents (CVA) in patients undergoing thoracic endovascular aortic repair (TEVAR). Between September 2000 and December 2006, 196 patients (135 men; mean age 68.6+/-13.5 years, range 17-92) underwent TEVAR for a variety of aortic pathologies. The majority (156, 79.6%) were treated with the TAG stent-graft. Demographics, pathologies, intraoperative procedure-related measures, device usage, and postoperative outcomes were assessed. CVA was defined as a new focal or global neurological (motor or sensory) deficit lasting >48 hours associated with acute intracranial abnormalities on computed tomography or magnetic resonance brain imaging. Spinal cord ischemia was excluded. In a subset of patients with planned left subclavian artery (LSA) coverage and an incomplete circle of Willis or a dominant left vertebral artery, prophylactic carotid-subclavian bypasses were performed. Nine (4.6%) patients suffered a CVA. Factors not predictive of a CVA on univariate analysis included aortic pathology, urgency of repair, ASA classification, type of anesthesia, blood loss, procedure time, and device used. Proximal extent of repair (with or without extra-anatomical revascularization) was significantly associated with a higher incidence of strokes (zones 0-2 versus 3-4, p=0.025). Five (55.6%) patients with a CVA had documented intraoperative hypotension (systolic blood pressure<80 mmHg). Additionally, while 2 patients had hemispheric infarcts, 5 had acute posterior circulation infarcts involving the cerebellum and brainstem; a single patient had both anterior and posterior circulation infarcts. Seven of the CVA patients had proximal coverage of the thoracic aorta in zones 0-2; of these, 6 had posterior circulation infarcts. Selective LSA revascularization based on preoperative cerebrovascular imaging resulted in lower rates of CVA (6.4% to 2.3%, p=0.30) and posterior circulation infarcts (5.5% to 1.2%, p=0.13). Proximal extent of repair may serve as a surrogate marker for greater severity of degenerative disease of the aortic arch. Avoidance of intraoperative hypotension and preservation of antegrade vertebral perfusion may be important in prevention of posterior circulation strokes.

High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. UK Medical Research Council, US National Institutes of Health.

BACKGROUNDThere is an unmet need to evaluate the burden of cardiometabolic risk factors in young South Asian adults, who are not preselected for glycaemia.AIMTo evaluate young North Indian men (aged 20-50 years) for burden of cardiometabolic risk factors, in relation to parameters of homeostatic model assessment for insulin resistance (HOMA-IR) and beta-cell function (oral disposition index [oDI]). METHODSStudy participants were invited in a fasting state. Sociodemographic, anthropometric, and medical data were collected, and 75 g oral glucose tolerance test was performed with serum insulin and plasma glucose estimation at 0, 30, and 120 min. Participants were divided into quartiles for HOMA-IR and oDI (category 1: Best HOMA-IR/oDI quartile; category 3: Worst HOMA-IR/oDI quartile) and composite HOMA-IR/oDI phenotypes (phenotype 1: Best quartile for both HOMA-IR and oDI; phenotype 4: Worst quartile for both HOMA-IR and oDI) were derived.RESULTSWe evaluated a total of 635 men at a mean (± SD) age of 33.9 ± 5.1 years and body mass index of 26.0 ± 3.9 kg/m2. Diabetes and prediabetes were present in 34 (5.4%) and 297 (46.8%) participants, respectively. Overweight/obesity, metabolic syndrome, and hypertension were present in 388 (61.1%), 258 (40.6%), and 123 (19.4%) participants, respectively. The prevalence of dysglycaemia, metabolic syndrome, and hypertension was significantly higher in participants belonging to the worst HOMA-IR and oDI quartiles, either alone (category 3 vs 1) or in combination (phenotype 4 vs 1). The adjusted odds ratios for dysglycaemia (6.5 to 7.0-fold), hypertension (2.9 to 3.6-fold), and metabolic syndrome (4.0 to 12.2-fold) were significantly higher in individuals in the worst quartile of HOMA-IR and oDI (category 3), compared to those in the best quartile (category 1). The adjusted odds ratios further increased to 21.1, 5.6, and 13.7, respectively, in individuals with the worst, compared to the best composite HOMA-IR/oDI phenotypes (phenotype 4 vs 1). CONCLUSIONThe burden of cardiometabolic risk factors is high among young Asian Indian men. Our findings highlight the importance of using parameters of insulin resistance and beta-cell function in phenotyping individuals for cardiometabolic risk.

Sex Differences in Early Carotid Atherosclerosis (from the Community-Based Gutenberg-Heart Study)

sponsorship: The European Union (HEALTH-F7-2011-278249 EU-MASCARA, HEALTH-F7-305507 HOMAGE and the European Research Council Advanced Researcher Grant 294713 EPLORE) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13 and G.0880.13) currently support the Studies Coordinating Centre (Leuven, Belgium). (European Union|HEALTH-F7-2011-278249 EU-MASCARA, European Union|HEALTH-F7-305507 HOMAGE, European Union (European Research Council)|294713 EPLORE, Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium|G.0881.13, Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium|G.0880.13)

OBJECT: This study was undertaken to evaluate the long-term angiographic outcome of surgically treated aneurysms, which is unknown. Specifically, the incidence of recurrent aneurysms, the fate of residual necks, and the de novo formation of aneurysms were evaluated. METHODS: One hundred two patients (80 females and 22 males; mean age 49 years; range 12-78 years) harboring a total of 167 aneurysms underwent late follow-up angiography; 160 aneurysms were surgically treated. Late angiographic follow-up review was obtained at a mean of 4.41.6 years postsurgery (range 2.6 -9.7 years). Late follow-up angiography revealed two recurrent aneurysms (1.5%) of 135 clipped aneurysms without residua. Of 12 aneurysms with known residua, there were eight "dog-ear" residua, of which two (25%) enlarged. One hemorrhage was noted, yielding a hemorrhage risk of 1.9% per year. A second subgroup with broad-based residua revealed dramatic regrowth in three of four cases. Eight de novo aneurysms were found in six patients, for an annual risk of 1.8% per year. A history of multiple aneurysms was associated with de novo aneurysm formation (p0.049, chi-square analysis). CONCLUSIONS: This study confirms the long-term efficacy of aneurysm clip ligation. In addition, the authors found there is a small but significant risk of de novo aneurysm formation, particularly in patients with multiple aneurysms. Most residual aneurysm rests appear to remain stable, although a subset may enlarge or rupture. These findings support the rationale for late angiographic follow-up review in patients with aneurysms.