Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies.

AIMS: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. METHODS AND RESULTS: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. CONCLUSION: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.

Does Low FEV1 in Addition to Fixed Ratio and/or Lower Limit of Normal of FEV1/FVC Improve Prediction of Mortality in COPD? The NHANES-III-linked-mortality Cohort.

PURPOSE: There is presently an ongoing debate on the relative merits of suggested criteria for spirometric airway obstruction. This study tests the null hypothesis that no superiority exists with the use of fixed ratio (FR) of forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) < 0.7 versus less than lower limit predicted (LLN) criteria with or without FEV1 <80% predicted in regards to future mortality. METHODS: In 1988-1994 the Third National Health and Nutrition Examination Survey (NHANES III) measured FEV1 and FVC with mortality follow-up data through December 31, 2011. For this survival analysis 7472 persons aged 40 and over with complete data formed the analytic sample. RESULTS: There were a total of 3554 deaths. Weighted Cox proportional hazards regression revealed an increased hazard ratio in persons with both fixed ratio and lower limit of normal with a low FEV1 (1.79, p < 0.0001), in those with fixed ratio only with a low FEV1 (1.77, p < 0.0001), in those with abnormal fixed ratio only with a normal FEV1 (1.28, p < 0.0001) compared with persons with no airflow obstruction (reference group). These remained significant after adjusting for demographic variables and other confounding variables. CONCLUSIONS: The addition of FEV1 < 80% of predicted increased the prognostic power of the fixed ratio <0.7 and/or below the lower limit of predicted criteria for airway obstruction.

Associations of Pulse and Blood Pressure with Hippocampal Volume by APOE and Cognitive Phenotype: The Alzheimer's Disease Neuroimaging Initiative (ADNI).

BACKGROUND: It is increasingly evident that high blood pressure can promote reduction in global and regional brain volumes. While these effects may preferentially affect the hippocampus, reports are inconsistent. METHODS: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we examined the relationships of hippocampal volume to pulse pressure (PPR) and systolic (SBP) and diastolic (DBP) blood pressure according to apolipoprotein (APOE) ɛ4 positivity and cognitive status. The ADNI data included 1,308 participants: Alzheimer disease (AD = 237), late mild cognitive impairment (LMCI = 454), early mild cognitive impairment (EMCI = 254), and cognitively normal (CN = 365), with up to 24 months of follow-up. RESULTS: Higher quartiles of PPR were significantly associated with lower hippocampal volumes (Q1 vs. Q4, p = 0.034) in the CN and AD groups, but with increasing hippocampal volume (Q1, p = 0.008; Q2, p = 0.020; Q3, p = 0.017; Q4 = reference) in the MCI groups. In adjusted stratified analyses among non-APOE ɛ4 carriers, the effects in the CN (Q1 vs. Q4, p = 0.006) and EMCI groups (Q1, p = 0.002; Q2, p = 0.013; Q3, p = 0.002; Q4 = reference) remained statistically significant. Also, higher DBP was significantly associated with higher hippocampal volume (p = 0.002) while higher SBP was significantly associated with decreasing hippocampal volume in the EMCI group (p = 0.015). CONCLUSION: Changes in PPR, SBP, and DBP differentially influenced hippocampal volumes depending on the cognitive and APOE genotypic categories.

Screen Hours and Sleep Symptoms: The US National Health and Nutrition Examination Survey.

Few studies have examined the relationship between television viewing, computer use, and sleep symptoms. We hypothesized that television and computer time was associated with sleep symptoms. Screen hours were the sum of daily TV hours and computer hours. A total of 4342 participants 20 years and older had data on screen hours. After adjusting for confounders, 4 or more screen hours were significantly associated with increased odds of reporting long sleep latency, nighttime awakening, high sleep hours, and snoring (P < .05). These findings suggest that increased screen/TV time is an important risk factor for sleep symptoms.

Incidence, Risk Factors and Outcomes of New Onset Supraventricular Arrhythmias in African American Patients with Severe Sepsis.

PURPOSE: New onset supraventricular arrhythmias (SVA) are commonly reported in mixed intensive care settings. We sought to determine the incidence, risk factors and outcomes of new onset SVA in African American (AA) patients with severe sepsis admitted to medical intensive care unit (MICU). METHODS: Patients admitted to MICU between January 2012 through December 2012 were studied. Patients with a previous history of arrhythmia or with new onset of ventricular arrhythmia were excluded. Data on risk factors, critical care interventions and outcomes were obtained. RESULTS: One hundred and thirty-one patients were identified. New onset SVA occurred in 34 (26%) patients. Of those 34, 20 (59%) had atrial fibrillation (AF), 6 (18%) had atrial flutter and 8 (24%) had other forms of SVA. Compared with patients without SVA, patients with new onset SVA were older (69 ± 12 yrs vs 59 ± 13 yrs, P=.003), had congestive heart failure (47% vs 24%, P=.015) and dyslipidemia (41% vs 15%, P=.002). Additionally, they had a higher mean mortality prediction model (MPM II) score (65 ± 25 vs 49 ± 26, P=.001) and an increased incidence of respiratory failure (85% vs 55%, P=.001). Hospital mortality in patients with new onset SVA was 18 (53%) vs 30 (31%); P=.024; however, in a multivariate analysis, new onset SVA was associated with non-significantly increased odds (OR 2.58, 95% CI 0.86-8.05) for in-hospital mortality. CONCLUSIONS: New onset SVA was prevalent in AA patients with severe sepsis and occurred more frequently with advanced age, increased severity of illness, congestive heart failure, and acute respiratory failure; it was associated with higher unadjusted in hospital mortality. However, after multiple adjustments, new onset SVA did not remain an independent predictor of mortality.

Soul Mates: Religion, Sex, Love, and Marriage among African Americans and Latinos.

INTRODUCTION: This book review analyzes the complex and profound impact active religious participation has on relationships and family outcomes among African Americans and Latinos. In Soul Mates, Wilcox and Wolfinger discuss the legacy of slavery and Jim Crow laws and the resulting devastating effects on African American and Latino families despite their high religious involvement. The authors make the case that many African American men are unlikely candidates for marriage or stable relationships due to trends of family instability driven by the declining income-power of working-class men as well as entry of more women into the labor force, government penalties for low-income couples, revolt against traditional values, increased access to birth control and abortion, and the persistence of discrimination and incarceration of minority men. METHODS: The authors examine data from six national surveys as well as additional data from interviews, focus groups, ethnographic field work, and an extensive literature review. RESULTS: Wilcox and Wolfinger find evidence that when African American couples actively participate in Christian churches, the men are more likely to adhere to a "code of decency" which decreases street behaviors, such as binge drinking, having multiple sex partners, and having multi-partner fertility, which are known to inhibit family stability. CONCLUSIONS: This book will be helpful for health providers who would like to better understand and serve their African American and Latino patients. The findings suggest that health care providers can promote a healthy emotional environment for families by encouraging minority men to renew or maintain church involvement.

Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study.

BACKGROUND: The global burden of atrial fibrillation (AF) is unknown. METHODS AND RESULTS: We systematically reviewed population-based studies of AF published from 1980 to 2010 from the 21 Global Burden of Disease regions to estimate global/regional prevalence, incidence, and morbidity and mortality related to AF (DisModMR software). Of 377 potential studies identified, 184 met prespecified eligibility criteria. The estimated number of individuals with AF globally in 2010 was 33.5 million (20.9 million men [95% uncertainty interval (UI), 19.5-22.2 million] and 12.6 million women [95% UI, 12.0-13.7 million]). Burden associated with AF, measured as disability-adjusted life-years, increased by 18.8% (95% UI, 15.8-19.3) in men and 18.9% (95% UI, 15.8-23.5) in women from 1990 to 2010. In 1990, the estimated age-adjusted prevalence rates of AF (per 100 000 population) were 569.5 in men (95% UI, 532.8-612.7) and 359.9 in women (95% UI, 334.7-392.6); the estimated age-adjusted incidence rates were 60.7 per 100 000 person-years in men (95% UI, 49.2-78.5) and 43.8 in women (95% UI, 35.9-55.0). In 2010, the prevalence rates increased to 596.2 (95% UI, 558.4-636.7) in men and 373.1 (95% UI, 347.9-402.2) in women; the incidence rates increased to 77.5 (95% UI, 65.2-95.4) in men and 59.5 (95% UI, 49.9-74.9) in women. Mortality associated with AF was higher in women and increased by 2-fold (95% UI, 2.0-2.2) and 1.9-fold (95% UI, 1.8-2.0) in men and women, respectively, from 1990 to 2010. There was evidence of significant regional heterogeneity in AF estimations and availability of population-based data. CONCLUSIONS: These findings provide evidence of progressive increases in overall burden, incidence, prevalence, and AF-associated mortality between 1990 and 2010, with significant public health implications. Systematic, regional surveillance of AF is required to better direct prevention and treatment strategies.

C-reactive protein, fibrinogen, and cardiovascular disease prediction.

BACKGROUND: There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. METHODS: We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. RESULTS: The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P<0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (<10%), "intermediate" (10% to <20%), and "high" (≥20%) (P<0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of ≥20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. CONCLUSIONS: In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.).

Effect modification by race-ethnicity of environmental tobacco smoke exposure on airway inflammation in US children.

BACKGROUND: Asthma mortality and morbidity are higher in black than in white children. Fractional exhaled nitric oxide (FeNO) is a noninvasive biomarker of eosinophilic airway inflammation. Identification of differences in the effect of environmental tobacco smoke (ETS) on airway inflammation by race and ethnicity from a large sample is needed. OBJECTIVE: To estimate a racial difference in association with ETS and FeNO. METHODS: Data from the 2007 to 2012 National Health and Nutrition Examination Survey were analyzed to compare associations of ETS and FeNO levels in US black and other children. No ETS exposure was defined as a serum cotinine level lower than 0.05 ng/mL and ETS exposure was defined as a serum cotinine level of at least 0.05 ng/mL. FeNO was measured using a device that relies on an electrochemical sensor. Analyses took the complex survey design into account. RESULTS: The analytic sample was formed by 5,473 participants (6-11 years old, n = 2,385; 12-19 years old, n = 3,088) with complete data on demographics, serum cotinine levels, and 2 reproducible FeNO measurements. In weighted linear regression analyses at 6 to 11 years, the interaction term for ETS and black race was not significant (P = .15). At 12 to 19 years, the interaction term was significant (P = .03) in an analysis of all racial groups. In race-specific models, the coefficient for ETS exposure in blacks was -0.033 and that in others was -0.175, ie, ETS exposure was associated with a greater decrease in FeNO in non-blacks than in blacks. CONCLUSION: There was no evidence at 6 to 11 years of age for an effect modification by race of the association between ETS and FeNO. At 12 to 19 years, the data suggested an effect modification.

Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Diabetes mellitus, fasting glucose, and risk of cause-specific death.

BACKGROUND: The extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain. METHODS: We calculated hazard ratios for cause-specific death, according to baseline diabetes status or fasting glucose level, from individual-participant data on 123,205 deaths among 820,900 people in 97 prospective studies. RESULTS: After adjustment for age, sex, smoking status, and body-mass index, hazard ratios among persons with diabetes as compared with persons without diabetes were as follows: 1.80 (95% confidence interval [CI], 1.71 to 1.90) for death from any cause, 1.25 (95% CI, 1.19 to 1.31) for death from cancer, 2.32 (95% CI, 2.11 to 2.56) for death from vascular causes, and 1.73 (95% CI, 1.62 to 1.85) for death from other causes. Diabetes (vs. no diabetes) was moderately associated with death from cancers of the liver, pancreas, ovary, colorectum, lung, bladder, and breast. Aside from cancer and vascular disease, diabetes (vs. no diabetes) was also associated with death from renal disease, liver disease, pneumonia and other infectious diseases, mental disorders, nonhepatic digestive diseases, external causes, intentional self-harm, nervous-system disorders, and chronic obstructive pulmonary disease. Hazard ratios were appreciably reduced after further adjustment for glycemia measures, but not after adjustment for systolic blood pressure, lipid levels, inflammation or renal markers. Fasting glucose levels exceeding 100 mg per deciliter (5.6 mmol per liter), but not levels of 70 to 100 mg per deciliter (3.9 to 5.6 mmol per liter), were associated with death. A 50-year-old with diabetes died, on average, 6 years earlier than a counterpart without diabetes, with about 40% of the difference in survival attributable to excess nonvascular deaths. CONCLUSIONS: In addition to vascular disease, diabetes is associated with substantial premature death from several cancers, infectious diseases, external causes, intentional self-harm, and degenerative disorders, independent of several major risk factors. (Funded by the British Heart Foundation and others.).

Cardiovascular disease mortality in Sub-Saharan Africa and the Caribbean.

Is there a full-blown stroke epidemic and a growing ischemic heart disease (IHD) epidemic in Sub-Saharan Africa? We aim to further understand the evolution of stroke and IHD in Sub-Saharan Africa with an analysis of the most recent Global Burden of Disease estimates of mortality for men of Sub-Saharan African descent in Africa and in the Caribbean and a review of recent studies found on PubMed and reference lists of published articles. Stroke is the most important cause of cardiovascular disease mortality in men aged 60-64 years in Africa and the Caribbean, but death rates and rank may vary by region. Ischemic heart disease is a leading cause in the Caribbean.

Gender and the association of smoking with sleep quantity and quality in American adults.

Smoking and gender are known risk factors for sleep disorders. Studies of samples from Norway and Japan have suggested stronger associations between smoking and disrupted sleep in women; therefore, we examined, gender differences in the association in the U.S. population. We analyzed data from the 2005-2006 National Health and Nutrition Examination Survey. We examined the associations between smoking and self-reported measures of sleep disorders (i.e., snoring, short sleep, long sleep, poor sleep, and health care provider diagnosis of sleep disordered breathing) using multivariate logistic regression with odds ratios (OR) and 95% confidence intervals (CI) as measures of association. We also assessed whether the associations varied by gender using a gender x smoking interaction term. Compared to never smokers, current smokers had significantly higher odds of self-reported snoring (OR = 2.0; 95% CI = 1.56-2.56), short sleep (OR 1.68; 95% CI = 1.35-2.10) and poor sleep (OR = 1.38; 95% CI = 1.09-1.74). A dose-response relationship was observed between the amount smoked and sleep symptoms. In multivariate analyses, no significant gender x smoking interaction was observed for snoring, short sleep or poor sleep. Current smoking was independently associated with increased odds of snoring, short sleep, and poor sleep in women and men among U.S. adults.

Prediction of individual lifetime cardiovascular risk and potential treatment benefit: development and recalibration of the LIFE-CVD2 model to four European risk regions.

AIMS: The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals. METHODS AND RESULTS: The updated LIFE-CVD (i.e. LIFE-CVD2) models were derived using individual participant data from 44 cohorts in 13 countries (687 135 individuals without established CVD, 30 939 CVD events in median 10.7 years of follow-up). LIFE-CVD2 uses sex-specific functions to estimate the lifetime risk of fatal and non-fatal CVD events with adjustment for the competing risk of non-CVD death and is systematically recalibrated to four distinct European risk regions. The updated models showed good discrimination in external validation among 1 657 707 individuals (61 311 CVD events) from eight additional European cohorts in seven countries, with a pooled C-index of 0.795 (95% confidence interval 0.767-0.822). Predicted and observed CVD event risks were well calibrated in population-wide electronic health records data in the UK (Clinical Practice Research Datalink) and the Netherlands (Extramural LUMC Academic Network). When using LIFE-CVD2 to estimate potential gain in CVD-free life expectancy from preventive therapy, projections varied by risk region reflecting important regional differences in absolute lifetime risk. For example, a 50-year-old smoking woman with a systolic blood pressure (SBP) of 140 mmHg was estimated to gain 0.9 years in the low-risk region vs. 1.6 years in the very high-risk region from lifelong 10 mmHg SBP reduction. The benefit of smoking cessation for this individual ranged from 3.6 years in the low-risk region to 4.8 years in the very high-risk region. CONCLUSION: By taking into account geographical differences in CVD incidence using contemporary representative data sources, the recalibrated LIFE-CVD2 model provides a more accurate tool for the prediction of lifetime risk and CVD-free life expectancy for individuals without previous CVD, facilitating shared decision-making for cardiovascular prevention as recommended by 2021 European guidelines.

The study introduces LIFE-CVD2, a new tool that helps predict the risk of heart disease over a person's lifetime, and highlights how where you live in Europe can affect this risk.Using health information from over 687 000 people, LIFE-CVD2 looks at things like blood pressure and whether someone smokes to figure out their chance of having heart problems later in life. Health information from another 1.6 million people in seven different European countries was used to show that it did a good job of predicting who might develop heart disease.Knowing your heart disease risk over your whole life helps doctors give you the best advice to keep your heart healthy. Let us say there is a 50-year-old woman who smokes and has a bit high blood pressure. Right now, she might not look like she is in danger. But with the LIFE-CVD2 tool, doctors can show her how making changes today, like lowering her blood pressure or stopping smoking, could mean many more years without heart problems. These healthy changes can make a big difference over many years.

Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies.

BACKGROUND: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. METHODS: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125,222 participants. We also compared the frequency of Asp358Ala in 51,441 patients with coronary heart disease and in 136,226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. FINDINGS: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4-38·2) and of interleukin 6 by 14·6% (10·7-18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9-9·1) and of fibrinogen by 1·0% (0·7-1·3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3·4% (1·8-5·0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. INTERPRETATION: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease. FUNDING: British Heart Foundation; UK Medical Research Council; UK National Institute of Health Research, Cambridge Biomedical Research Centre; BUPA Foundation.

Racial and geographic variation in coronary heart disease mortality trends.

BACKGROUND: Magnitudes, geographic and racial variation in trends in coronary heart disease (CHD) mortality within the US require updating for health services and health disparities research. Therefore the aim of this study is to present data on these trends through 2007. METHODS: Data for CHD were analyzed using the US mortality files for 1999-2007 obtained from the US Centers for Disease Control and Prevention. Age-adjusted annual death rates were computed for non-Hispanic African Americans (AA) and European Americans (EA) aged 35-84 years. The direct method was used to standardize rates by age, using the 2000 US standard population. Joinpoint regression models were used to evaluate trends, expressed as annual percent change (APC). RESULTS: For both AA men and women the magnitude in CHD mortality is higher compared to EA men and women, respectively. Between 1999 and 2007 the rate declined both in AA and in EA of both sexes in every geographic division; however, relative declines varied. For example, among men, relative average annual declines ranged from 3.2% to 4.7% in AA and from 4.4% to 5.5% in EA among geographic divisions. In women, rates declined more in later years of the decade and in women over 54 years. In 2007, age-adjusted death rate per 100,000 for CHD ranged from 93 in EA women in New England to 345 in AA men in the East North Central division. In EA, areas near the Ohio and lower Mississippi Rivers had above average rates. Disparities in trends by urbanization level were also found. For AA in the East North Central division, the APC was similar in large central metro (-4.2), large fringe metro (-4.3), medium metro urbanization strata (-4.4), and small metro (-3.9). APC was somewhat higher in the micropolitan/non-metro (-5.3), and especially the non-core/non-metro (-6.5). For EA in the East South Central division, the APC was higher in large central metro (-5.3), large fringe metro (-4.3) and medium metro urbanization strata (-5.1) than in small metro (-3.8), micropolitan/non-metro (-4.0), and non-core/non-metro (-3.3) urbanization strata. CONCLUSIONS: Between 1999 and 2007, the level and rate of decline in CHD mortality displayed persistent disparities. Declines were greater in EA than AA racial groups. Rates were greater in the Ohio and Mississippi River than other geographic regions.

Lipid-related markers and cardiovascular disease prediction.

CONTEXT: The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated. OBJECTIVE: To determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction. DESIGN, SETTING, AND PARTICIPANTS: Individual records were available for 165,544 participants without baseline CVD in 37 prospective cohorts (calendar years of recruitment: 1968-2007) with up to 15,126 incident fatal or nonfatal CVD outcomes (10,132 CHD and 4994 stroke outcomes) during a median follow-up of 10.4 years (interquartile range, 7.6-14 years). MAIN OUTCOME MEASURES: Discrimination of CVD outcomes and reclassification of participants across predicted 10-year risk categories of low (<10%), intermediate (10%-<20%), and high (≥20%) risk. RESULTS: The addition of information on various lipid-related markers to total cholesterol, HDL-C, and other conventional risk factors yielded improvement in the model's discrimination: C-index change, 0.0006 (95% CI, 0.0002-0.0009) for the combination of apolipoprotein B and A-I; 0.0016 (95% CI, 0.0009-0.0023) for lipoprotein(a); and 0.0018 (95% CI, 0.0010-0.0026) for lipoprotein-associated phospholipase A2 mass. Net reclassification improvements were less than 1% with the addition of each of these markers to risk scores containing conventional risk factors. We estimated that for 100,000 adults aged 40 years or older, 15,436 would be initially classified at intermediate risk using conventional risk factors alone. Additional testing with a combination of apolipoprotein B and A-I would reclassify 1.1%; lipoprotein(a), 4.1%; and lipoprotein-associated phospholipase A2 mass, 2.7% of people to a 20% or higher predicted CVD risk category and, therefore, in need of statin treatment under Adult Treatment Panel III guidelines. CONCLUSION: In a study of individuals without known CVD, the addition of information on the combination of apolipoprotein B and A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 mass to risk scores containing total cholesterol and HDL-C led to slight improvement in CVD prediction.

Fractional exhaled nitric oxide and mortality in asthma and chronic obstructive pulmonary disease in a national cohort aged 40 years and older.

BACKGROUND: Little is known about Fractional concentration of exhaled Nitric Oxide (FeNO) as a predictor of mortality in persons with asthma or chronic obstructive pulmonary disease (COPD). OBJECTIVE: This study tested the hypotheses that FeNO level ≥ 25 ppb was associated with mortality in a national cohort of persons with asthma or COPD age ≥ 40 years. METHODS: In the 2007-2012 National Health and Nutrition Examination Survey (NHANES), FeNO was measured using an electrochemical sensor. Mortality was determined through 2015 using linkage to the National Death Index. Weighted Cox proportional hazards survival analysis was performed taking the complex survey design into account using STATA V.17. RESULTS: Among the 611 participants with current asthma, 5.16% died during the follow-up period. FeNO ≥ 25 ppb was associated with a hazard ratio (HR) of 0.20, (p = 0.006, 95% CI:0.068-0.618) alone or with little change after controlling for confounding variables. Due to effect modification, the analysis was repeated in persons with and without a history of emergency department (ED) visit for asthma in the previous year. In 522 persons without ED visits, FeNO ≥ 25 ppb was significantly associated with mortality HR 0.094, 95 CI 0.034-0.26, p < 0.001. In 83 persons with ED visits no significant association remained after controlling for all confounders. (Six persons were omitted from this analysis due to missing data on confounders in the extended regression model.) Among 614 with COPD, FeNO ≥ 25 ppb was not associated with mortality. CONCLUSION: In persons with current asthma at baseline, FeNO ≥ 25 ppb was associated with reduced hazard of mortality during follow up among those with no history of ED visits in the previous year. No significant association of FeNO with mortality was seen in persons with COPD.