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.

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.

Geographic Heterogeneity in Influenza and Pneumonia Mortality in Hispanic Americans.

(1) Background: Influenza and pneumonia (IP) is a leading cause of death in the US. The hypothesis was tested that the mortality rate differential between Hispanic whites (HW) and non-Hispanic whites (NHW) from IP varied by geographic region in the US. (2) Methods: The CDC database for multiple causes of death between 1999-2018 was used for this study. For ages 25-84, age-adjusted mortality rates per 100,000 (AAMR) for IP were computed by Hispanic ethnicity in whites for 10 Health & Human Services (HHS) regions and for urbanization levels in HHS Region 2. (3) Results: AAMR for IP was 13.76 (13.62-13.9) in HW and 14.91 (14.86-14.95) in NHW (rate ratio 1.08). Among HHS regions, rates were generally lower in HW than in NHW with the major exception of HHS Region 2. The rate there was 21.78 (21.24-22.33) in HW, 36.5% greater (p < 0.05) than that in NHW of 15.71 (15.56-15.86). In large central metro areas of Region 2, the rate was 27.10 (26.36-27.83) in HW compared to 19.78 (19.47-20.09) in NHW. (4) Conclusion: The difference in AAMR from IP between HW and NHW varied by region and urbanization with much higher rates for HW than NHW only in metropolitan areas of New York and New Jersey.

Geographic Variation in Racial Disparities in Mortality From Influenza and Pneumonia in the United States in the Pre-Coronavirus Disease 2019 Era.

BACKGROUND: In 2018, influenza and pneumonia was the eighth leading cause of death in the United States. Since 1950, non-Hispanic blacks (NHBs) have experienced higher rates of mortality than non-Hispanic whites (NHWs). Previous studies have revealed geographic variation in mortality rates by race. The identification of areas with the greatest disparity in influenza and pneumonia mortality may assist policymakers in the allocation of resources, including for the coronavirus disease 2019 pandemic. RESEARCH QUESTION: Does geographic variation in racial disparity in influenza and pneumonia mortality exist? STUDY DESIGN AND METHODS: The Centers for Disease Control and Prevention database for Multiple Cause of Death between 1999 and 2018 for NHB and NHW decedents ≥ 25 years of age with a Tenth Revision of the International Statistical Classification of Diseases and Related Health Problems code for influenza (J09-J11) and pneumonia (J12-J18) was used. Age-adjusted mortality rates (AAMRs) with 95% CIs were computed by race for Health & Human Services (HHS) regions and urbanization in NHBs and NHWs. RESULTS: In 1999 through 2018, there were 540,476 deaths among NHBs and NHWs 25 to 84 years of age. AAMRs were higher in NHBs than NHWs in each age group and in seven of 10 HHS regions. The greatest disparity was in HHS regions 2 (New York and New Jersey) and 9 (Arizona, California, Hawaii, and Nevada). In HHS region 2, NHBs (24.6; 95% CI, 24.1-25.1) were more likely to die than NHWs (15.7; 95% CI, 15.6-15.9). Similarly, in region 9, NHBs (23.2; 95% CI, 22.7-23.8) had higher mortality than NHWs (16.1; 95% CI, 15.9-16.2). Within these regions, disparities were greatest in the core of major metropolitan areas. A very high AAMR in NHBs was noted in large, central metropolitan areas of region 2: 28.2 (95% CI, 27.6-28.9). INTERPRETATION: In 1999 through 2018, the NHB-NHW disparity in AAMRs from influenza and pneumonia was greatest in central metropolitan areas of HHS regions 2 and 9.

Atherosclerotic Peripheral Artery Disease in the United States: Gender and Ethnic Variation in a Multiple Cause-of-Death Analysis.

BACKGROUND: Atherosclerotic peripheral artery disease (PAD) is an important cause of morbidity in the United States. In this article, we conducted a multiple cause-of-death analysis of PAD to determine patterns and trends in its contribution to mortality. METHODS: The Centers for Disease Control and Prevention statistics data were used to determine the number of deaths with the following 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes selected as an underlying cause of death (UCOD) or a contributing cause considering multiple causes of death (MCOD): 170.2, 170.9, 173.9, 174.3, and 174.4. The age-adjusted death rates per 100 000 population by age, gender, race, ethnicity, and region were computed for the United States between the years 1999 and 2017. In these years, there were 47 728 569 deaths from all causes. RESULTS: In 1999 to 2017 combined, there were a total of 311 175 deaths associated with PAD as an UCOD. However, there were 1 361 253 deaths with PAD listed as an UCOD or a contributing cause in MCOD, which is 4.3 times higher than UCOD. Age-adjusted MCOD rates were higher in males (25.6) than in females (19.4). Among non-Hispanics, the rate in African American males and females was 1.2 times higher than in Caucasians. Age-adjusted MCOD rates have declined in African Americans and Caucasians irrespective of gender from 2000 to 2017. CONCLUSION: Peripheral artery disease is mentioned 4 times as often on death certificates as a contributing cause of death as it is chosen as the UCOD. Overall, age-adjusted MCOD rates were higher in African Americans than Caucasians, males than females, and declined between 2000 and 2017.

Exercise Training Induced Changes In Nuclear Magnetic Resonance-Measured Lipid Particles In Mild Cognitively Impaired Elderly African American Volunteers: A Pilot Study.

PURPOSE: Poor cardiorespiratory fitness (CRF) is linked to cognitive deterioration, but its effects on lipid heterogeneity and functional properties in older African American (AA) subjects with mild cognitive impairment (MCI) need elucidation. This study determined whether exercise training-induced changes in blood lipid particle sizes (LPS) were associated with CRF determined by VO2Max in elderly AAs with MCI. Given the pivotal role of brain-derived neurotrophic factor (BDNF) on glucose metabolism, and therefore, "diabetic dyslipidemia", we also determined whether changes in LPS were associated with the levels of serum BDNF. METHODS: This analysis included 17 of the 29 randomized elderly AAs with MCI who had NMR data at baseline and after a 6-month training. We used Generalized Linear Regression (GLM) models to examine cardiorespiratory fitness (VO2Max) effects on training-induced change in LPS in the stretch and aerobic groups. Additionally, we determined whether the level of BDNF influenced change in LPS. RESULTS: Collectively, mean VO2Max (23.81±6.17) did not differ significantly between aerobic and stretch groups (difference=3.17±3.56, P=0.495). Training-related changes in very low-density lipoprotein, chylomicrons, and total low-density lipoprotein (LDL) particle sizes correlated significantly with VO2Max, but not after adjustment for age and gender. However, increased VO2Max significantly associated with reduced total LDL particle size after similar adjustments (P = 0.046). While stretch exercise associated with increased protective large high-density lipoprotein particle size, the overall effect was not sustained following adjustments for gender and age. However, changes in serum BDNF were associated with changes in triglyceride and cholesterol transport particle sizes (P < 0.051). CONCLUSION: Promotion of stretch and aerobic exercise to increase CRF in elderly AA volunteers with MCI may also promote beneficial changes in lipoprotein particle profile. Because high BDNF concentration may reduce CVD risk, training-related improvements in BDNF levels are likely advantageous. Large randomized studies are needed to confirm our observations and to further elucidate the role for exercise therapy in reducing CVD risk in elderly AAs with MCI.

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.

Burden of Peripheral Artery Disease in Sub-Saharan Africa and the Caribbean 1990 to 2015.

BACKGROUND: The estimated global prevalence of Peripheral artery disease (PAD) increased by 24% in span of 10 years (2000-2010) from 164 to 202 million. Despite scarcity of data on PAD in sub-Saharan Africa (SSA) and the Caribbean, estimates for PAD from these regions may be helpful for health-care providers. METHODS: The Global Burden of Disease Study 2015 quantified health loss from hundreds of diseases using systematic reviews and multilevel computer modeling. Estimated rates with 95% uncertainty intervals (UI) for PAD (ICD-10 I70.2) were examined for SSA and the Caribbean and compared to high-income North America (HINA). Disability-adjusted life years (DALYs) are years of healthy life lost representing total disease burden by combining years of life lost and years lived disabled. RESULTS: In 2015, estimated age-standardized DALYs per 100,000 due to PAD for males were as follows: Caribbean (34, UI: 29-39), HINA (36, UI: 30-42), and SSA (20, UI: 14-30). In contrast, DALYs in females were as follows: Caribbean (25, UI: 20-30), HINA (28, UI: 22-36), and SSA (17, UI: 11-26). For both sexes combined, the rate in Southern SSA was 55 (46-67). This reflects the extremely high rates in South Africa (males 90, UI: 77-107; females 63, UI: 53-75). CONCLUSION: Estimated rate of DALYs per 100,000 was lowest in SSA. Within SSA, the rate in South Africa was highest, exceeding even HINA. Caribbean rates were intermediate.

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.

The Burden of Cardiovascular Disease in Sub-Saharan Africa and the Black Diaspora.

For over four decades the National Medical Association (NMA) and the Association of Black Cardiologists (ABC) have sought to bring to national attention the disparate burden of cardiovascular disease (CVD) among African Americans. However, systematic inquiry has been inadequate into the burden of CVD in the poor countries of Sub-Saharan Africa (SSA) and the African diaspora in the Americas outside the USA. However, recently, the Global Burden of Disease Study (GBD) has offered new tools for such inquiry. Several initial efforts in that direction using 2010 data have been published. This article highlights some new findings for SSA for 2016. It also suggests that NMA and ABC further this effort by direct advocacy and collaboration with the GBD to make estimates of CVD burden in African Americans and South American Blacks explicitly available in future iterations.

Airflow obstruction, cognitive function and mortality in a US national cohort: NHANES-III.

OBJECTIVE: To test the hypothesis that cognitive impairment increases mortality independent of airflow obstruction. MATERIALS AND METHODS: In 1988-1994 the Third National Health and Nutrition Examination Survey (NHANES III) measured forced expiratory volume in the first second (FEV1) and the forced vital capacity (FVC) and selected items on cognitive function with mortality follow-up. For this survival analysis 4365 persons aged 60 and over with complete data formed the analytic sample. RESULTS: The FEV1/FVC less than the lower limit of predicted ratio (LLP) defined airflow obstruction and Composite Cognitive Function Score (CCF) ≤4, cognitive impairment. The percentage who died during follow up was 67% among those with neither FEV1/FVC < LLP nor CCF ≤4, 82% with FEV1/FVC < LLP only, 85% with CCF score ≤4 only and 93% with both FEV1/FVC LLP and CCF score ≤4 (P < .001). Weighted Cox proportional hazards regression revealed an increased hazard ratio (HR) in persons with FEV1/FVC

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.

APOEε4 impacts up-regulation of brain-derived neurotrophic factor after a six-month stretch and aerobic exercise intervention in mild cognitively impaired elderly African Americans: A pilot study.

Possession of the Apolipoprotein E (APOE) gene ε4 allele is the most prevalent genetic risk factor for late onset Alzheimer's disease (AD). Recent evidence suggests that APOE genotype differentially affects the expression of brain-derived neurotrophic factor (BDNF). Notably, aerobic exercise-induced upregulation of BDNF is well documented; and exercise has been shown to improve cognitive function. As BDNF is known for its role in neuroplasticity and survival, its upregulation is a proposed mechanism for the neuroprotective effects of physical exercise. In this pilot study designed to analyze exercise-induced BDNF upregulation in an understudied population, we examined the effects of APOEε4 (ε4) carrier status on changes in BDNF expression after a standardized exercise program. African Americans, age 55years and older, diagnosed with mild cognitive impairment participated in a six-month, supervised program of either stretch (control treatment) or aerobic (experimental treatment) exercise. An exercise-induced increase in VO2Max was detected only in male participants. BDNF levels in serum were measured using ELISA. Age, screening MMSE scores and baseline measures of BMI, VO2Max, and BDNF did not differ between ε4 carriers and non-ε4 carriers. A significant association between ε4 status and serum BDNF levels was detected. Non-ε4 carriers showed a significant increase in BDNF levels at the 6month time point while ε4 carriers did not. We believe we have identified a relationship between the ε4 allele and BDNF response to physiologic adaptation which likely impacts the extent of neuroprotective benefit gained from engagement in physical exercise. Replication of our results with inclusion of diverse racial cohorts, and a no-exercise control group will be necessary to determine the scope of this association in the general population.

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.