Abstract P217: Coagulation Factor IX Levels and Risk of Stroke and Coronary Heart Disease: The REasons for Geographic And Racial Differences in Stroke Study (REGARDS)

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Nels C Olson ◽  
Mary Cushman ◽  
Suzanne Judd ◽  
Brett Kissela ◽  
Monika M Safford ◽  
...  

Introduction: The role of coagulation in coronary heart disease (CHD) and stroke remains controversial. We examined the association of levels of coagulation factor IX (FIX) with incident CHD and ischemic stroke in REGARDS. Methods: REGARDS recruited 30,239 participants in their homes across the contiguous U.S. between 2003-07; by design 41% were black, 55% female, and 56% lived in the southeast. Levels of FIX were measured in participants with incident CHD (n=654), incident stroke (n=646), and in a cohort random sample (n=1,104). Cox models were used to calculate the hazard ratio (HR) per standard deviation (SD) higher FIX level for incident CHD and stroke adjusting for traditional cardiovascular disease (CVD) risk factors, and testing a race by FIX interaction term. Participants with hemorrhagic stroke were excluded from the stroke analyses (n=73). Results: Levels of FIX were higher with increasing age, black race, female gender, diabetes, hypertension, dyslipidemia, and among those living in the southeastern U.S. (all p<0.0001). As shown in the table, FIX levels (per 1 SD higher) were associated with CHD, but not stroke, after adjustment for CVD risk factors. When stratified by race, the association with CHD was stronger in blacks than whites (p-interaction = 0.08) with no association for stroke in either blacks or whites (p-interaction 0.71). Analyses of FIX by quintiles did not alter the results. Discussion: Levels of coagulation factor IX were significantly associated with incident CHD, but not stroke in blacks but not whites, after adjustment for CVD risk factors. These data suggest that higher levels of FIX are a risk factor for CHD in blacks but not whites, and may indicate different roles for hemostasis in vascular disease risk by race and by vascular disease type.

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Stephen P Glasser ◽  
Daniel L Halberg ◽  
Charles Sands ◽  
Paul Muntner ◽  
Monika Safford

Background: Increased attention has been given to pulse pressure (PP) as a potential independent risk factor of cardiovascular disease. We examined the relationship between PP and incident acute coronary heart disease (CHD). Methods: We used data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study of 30,239 black and white participants aged 45 years or older and enrolled between 2003 and 2007. Baseline data included a 45-minute interview and in-home visit during which blood pressure was assessed and recorded as the average of two measurements obtained after a 5 minute seated rest. PP (SBP-DBP) was classified into 4 groups (<45, 45-54, 54.1-64, >64.1 mmHg). Telephone follow-up occurred every six months for self or proxy-reported suspected events, triggering medical record retrieval and adjudication by experts. Cox-proportional hazards models examined the association of incident CHD with PP groups, adjusting for socio-demographic and clinical risk factors. Results: This analysis included 22,909 participants free of CHD at baseline, with mean age 64.7±9.4 years; 40.4%were black, 44.6% were male and they experienced a total of 515 incident CHD events over a mean 3.4 yrs of follow-up (maximum 6 years). In unadjusted analyses, compared with PP<45 mmHg, each higher PP group had incrementally higher hazard ratios (HR) for incident CHD (HR 1.28 {95% CI 1.02-1.60}, 2.05 {1.63-2.56}, 3.82 {3.08-4.74}, p<0.001 for linear trend). This relationship persisted after fully adjusting including SBP for the highest PP group (HR 0.96 {0.75-1.21}, 1.12 {0.86-1.46}, 1.51 {1.09-2.10}, p trend <0.0001). Conclusions: High PP was associated with incident CHD, even when accounting for SBP and numerous other CVD risk factors.


2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Victor Okunrintemi ◽  
Martin Tibuakuu ◽  
Salim S. Virani ◽  
Laurence S. Sperling ◽  
Annabelle Santos Volgman ◽  
...  

Background Sex differences in the trends for control of cardiovascular disease (CVD) risk factors have been described, but temporal trends in the age at which CVD and its risk factors are diagnosed and sex‐specific differences in these trends are unknown. Methods and Results We used the Medical Expenditure Panel Survey 2008 to 2017, a nationally representative sample of the US population. Individuals ≥18 years, with a diagnosis of hypercholesterolemia, hypertension, coronary heart disease, or stroke, and who reported the age when these conditions were diagnosed, were included. We included 100 709 participants (50.2% women), representing 91.9 million US adults with above conditions. For coronary heart disease and hypercholesterolemia, mean age at diagnosis was 1.06 and 0.92 years older for women, compared with men, respectively (both P <0.001). For stroke, mean age at diagnosis for women was 1.20 years younger than men ( P <0.001). The mean age at diagnosis of CVD risk factors became younger over time, with steeper declines among women (annual decrease, hypercholesterolemia [women, 0.31 years; men 0.24 years] and hypertension [women, 0.23 years; men, 0.20 years]; P <0.001). Coronary heart disease was not statistically significant. For stroke, while age at diagnosis decreased by 0.19 years annually for women ( P =0.03), it increased by 0.22 years for men ( P =0.02). Conclusions The trend in decreasing age at diagnosis for CVD and its risk factors in the United States appears to be more pronounced among women. While earlier identification of CVD risk factors may provide opportunity to initiate preventive treatment, younger age at diagnosis of CVD highlights the need for the prevention of CVD earlier in life, and sex‐specific interventions may be needed.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255786
Author(s):  
Marina Rudman ◽  
Mirjam Frank ◽  
Carina Emmel ◽  
Emanuel Matusch ◽  
Kaffer Kara ◽  
...  

Objectives N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) is a diagnostic marker for heart failure and a prognostic factor for cardiovascular disease (CVD). The aim of this study was to examine the association of socioeconomic position (SEP) with NT-proBNP while assessing sex-differences and the impact of CVD risk factors and prevalent CVD on the association. Methods Baseline data of 4598 participants aged 45–75 years of the Heinz Nixdorf Recall Study were used. Income and education were used as SEP indicators. Age- and sex-adjusted linear regression models were fitted to calculate effect size estimates and 95% confidence intervals (95%-CIs) for the total effect of SEP indicators on NT-proBNP, while potential mediation was assessed by additionally accounting for traditional CVD risk factors (i.e., systolic blood pressure, HDL cholesterol, LDL cholesterol, diabetes, anti-hypertensive medication, lipid-lowering medication, BMI, current smoking). Education and income were included separately in the models. Results With an age- and sex-adjusted average change in NT-proBNP of -6.47% (95%-CI: -9.91; -2.91) per 1000€, the association between income and NT-proBNP was more pronounced compared to using education as a SEP indicator (-0.80% [95%-CI: -1.92; 0.32] per year of education). Sex-stratified results indicated stronger associations in men (-8.43% [95%-CI: -13.21; -3.38] per 1000€; -1.63% [95%-CI: -3.23; -0.001] per year of education) compared to women (-5.10% [95%-CI: -9.82; -0.01] per 1000€; -1.04% [95%-CI: -2.59; 0.50] per year of education). After adjusting for CVD risk factors some of the observed effect size estimates were attenuated, while the overall association between SEP indicators and NT-proBNP was still indicated. The exclusion of participants with prevalent coronary heart disease or stroke did not lead to a substantial change in the observed associations. Conclusions In the present study associations of education and income with NT-proBNP were observed in a population-based study sample. Only parts of the association were explained by traditional CVD risk factors, while there were substantial sex-differences in the strength of the observed association. Overt coronary heart disease or stroke did not seem to trigger the associations.


2020 ◽  
Author(s):  
Paul Welsh ◽  
Claire Welsh ◽  
Carlos A Celis-Morales ◽  
Rosemary Brown ◽  
Lyn D Ferguson ◽  
...  

AbstractBackgroundLipoprotein (a) (Lp(a)) is a CVD risk factor amenable to intervention and might help guide risk prediction.ObjectivesTo investigate the population attributable fraction due to elevated Lp(a) and its utility in risk prediction.MethodsUsing a prospective cohort study, 413,724 participants from UK Biobank, associations of serum Lp(a) with composite fatal/nonfatal CVD (n=10,065 events), fatal CVD (n=3247), coronary heart disease (n=16,649), ischaemic stroke (n=3191), and peripheral vascular disease (n=2716) were compared using Cox models. Predictive utility was determined by C-index changes. The population attributable fraction was estimated.ResultsMedian Lp(a) was 19.7nmol/L (interquartile interval 7.6-75.3nmol/L). 20.8% had Lp(a) values >100nmol/L; 9.2% had values >175nmol/L. After adjustment for classical risk factors, in participants with no baseline CVD and not taking a statin, 1 standard deviation increment in log Lp(a) was associated with a HR for fatal/nonfatal CVD of 1.09 (95%CI 1.07-1.11). Associations were similar for fatal CVD, coronary heart disease, and peripheral vascular disease. Adding Lp(a) to a prediction model containing traditional CVD risk factors improved the C-index by +0.0017 (95% CI 0.0009, 0.0026). We estimated that having Lp(a) values >100nmol/L accounts for 5.7% of CVD events in the whole cohort. We modelled that an ongoing trial to lower Lp(a) in patients with CVD and Lp(a) above ∼175nmol/L may reduce CVD risk by 20.3%, assuming causality, and an achieved Lp(a) reduction of 80%.ConclusionsPopulation screening for elevated Lp(a) may help to predict CVD and target Lp(a) lowering drugs, if such drugs prove efficacious, to those with markedly elevated levels.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Welsh ◽  
C Welsh ◽  
C.A.C Celis-Morales ◽  
R Brown ◽  
L.D Ferguson ◽  
...  

Abstract Background Lipoprotein (a) (Lp(a)) measurement may help guide CVD risk prediction, is thought to be causal in several CVD outcomes, and phase 3 intervention trials of Lp(a) lowering agents are underway. We aimed to investigate the population attributable fraction due to elevated Lp(a) and its utility in CVD risk prediction. Methods In 413,724 participants from UK Biobank, associations of serum Lp(a) with composite fatal/nonfatal CVD (n=10,065 events), fatal CVD (n=3247), coronary heart disease (n=16,649), ischaemic stroke (n=3191), and peripheral vascular disease (n=2716) were compared using Cox models. Predictive utility was determined by C-index changes. The population attributable fraction was estimated. Results Median Lp(a) was 19.7nmol/L (interquartile interval 7.6–75.3nmol/L). 20.8% had Lp(a) values &gt;100nmol/L; 9.2% had values &gt;175nmol/L. After adjustment for classical risk factors, in participants with no baseline CVD and not taking a statin, 1 standard deviation increment in log Lp(a) was associated with a HR for fatal/nonfatal CVD of 1.09 (95% CI 1.07–1.11). Associations were similar for fatal CVD, coronary heart disease, and peripheral vascular disease. Adding Lp(a) to a prediction model containing traditional CVD risk factors improved the C-index by +0.0017 (95% CI 0.0009, 0.0026). We estimated that having Lp(a) values &gt;100nmol/L accounts for 5.7% of CVD events in the whole cohort. We modelled that an ongoing trial to lower Lp(a) in patients with CVD and Lp(a) above ∼175nmol/L may be expected to reduce CVD risk by 20.3%, assuming causality, and an achieved Lp(a) reduction of 80%. Conclusions Population screening for elevated Lp(a) may help to predict CVD and target Lp(a) lowering drugs to those with markedly elevated levels, if such drugs prove efficacious. Population attributable fractions: Lp(a) Funding Acknowledgement Type of funding source: Other. Main funding source(s): Chest, Heart, and Stroke Association Scotland and British Heart Foundation


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Neil A Zakai ◽  
George Howard ◽  
Leslie A McClure ◽  
Suzanne E Judd ◽  
Brett M Kissela ◽  
...  

Introduction: D-dimer, a marker of coagulation activation, has higher levels in blacks than whites and has been variably associated with stroke and coronary heart disease (CHD). Methods: REGARDS recruited 30,239 participants in their homes across the continental US between 2003-07; by design 55% were female, 41% black, and 56% lived in the southeast. In a case-cohort study, D-dimer was measured in 646 participants with incident stroke, 515 with incident CHD, and 1104 in a cohort random sample. D-dimer was log transformed and modeled per 1-unit increase. Cox models were used to determine the HR for vascular disease for D-dimer and the difference in HR (95% CI) by race and vascular disease calculated by bootstrapping with 1000 replicate samples and using the 2.5 and 97.5 percentiles of the distribution (see Table for model variables). Results: Median D-dimer was higher in blacks (0.45 mcg/mL; IQR 0.26, 0.85) than whites (0.38 mcg/mL; IQR 0.23, 0.69); p <0.001. D-dimer was higher with increasing age, female gender, diabetes, hypertension and prebaseline cardiovascular disease (all p <0.05). The table shows the HR of stroke and CHD by baseline D-dimer. In minimally-adjusted models, D-dimer was associated with both stroke and CHD. Accounting for Framingham stroke and CHD risk factors, D-dimer remained associated with CHD (HR 1.45; 95% CI 1.18, 1.79), but was marginally associated with stroke (HR 1.20; 95% CI 0.99, 1.45). The difference in the HR of D-dimer between CHD and stroke was 0.22 in the basic model and 0.25 in the Framingham model, but this difference was of marginal statistical significance (Table). There was no difference in the HRs for stroke or CHD for D-dimer in blacks compared to whites (Table). Discussion: The association of D-dimer with stroke appeared smaller than for CHD with similar associations by race. Findings suggest that hemostasis activation may play a greater role in pathogenesis of CHD than stroke. Further study is needed to confirm these findings and evaluate the association of D-dimer with different stroke subtypes.


VASA ◽  
2008 ◽  
Vol 37 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Fronek ◽  
Allison

Background: The aim of this study was first to compare the widely used flow mediated dilation ( FMD ) method with the iontophoretically induced acetylcholine vasodilation (IAV ) procedure. The ultimate goal was to examine the endothelial activity ( EA ) in patients with various cardiovascular risk factors compared with control subjects. Patients and methods: In the upper extremities of 27 subjects, comparisons of EA by FMD and IAV measured with laser Doppler flux method (LDF) were conducted. IAV-EA was then measured using LDF in an additional 93 subjects with various cardiovascular ( CVD ) risk factors and/or a diagnosis of coronary heart disease (CHD). Results: The mean age of the subjects was 56.2 years and 54% were male. There was a robust and significant correlation between FMD vs IAV endothelial activity (r = 0.87, p = 0.025). After adjustment for age, there were significant differences in LDF-measured, acetylcholine-induced EA by diagnosis of CHD (p = 0.02), hyperlipidemia (p = 0.03) and diabetes (p < 0.01), as well as by sex (p < 0.01). The difference by hypertension status was of borderline significance (p = 0.07). LDF EA was higher in non-smokers compared to smokers but this difference was not statistically significant (p = 0.3). After adjustment for age and gender, a 10-unit increase in LDF-measured EA was associated with a 12% lower odds for a diagnosis of CHD (p = 0.07). Conclusions: Measurement of IAV-EA by LDF is a simple, noninvasive methodology which is highly correlated with post-occlusive FMD EA and is also significantly associated with a diagnosis of CHD.


2008 ◽  
Vol 33 (2) ◽  
pp. 282-289 ◽  
Author(s):  
M.O. Ebesunun ◽  
E.O. Agbedana ◽  
G.O.L. Taylor ◽  
O.O. Oladapo

Elevated plasma lipoprotein (a) (Lp(a)) and total homocysteine (tHcy) concentrations, as well as fat distributions, are associated with cardiovascular disease (CVD) risk. The purpose of this study was to evaluate plasma Lp(a), tHcy, percentage body fat, anthropometric indices, and blood pressure (BP) and their relationships with each other in well-defined, hospital-based, CVD patients in a Nigerian African community. One hundred seventy patients suffering from hypertensive heart disease, hypertension, ischaemic heart disease, and myocardial infraction with the mean age of 45.3 ± 1.3 years and 58 apparently healthy volunteers with the mean age of 44.8 ±1.2 years were selected. Anthropometric indices and BP were measured. Percentage body fat, body mass index, and waist-to-hip ratio (WHR) were calculated. Plasma Lp(a) and tHcy concentrations were determined. The results showed significant increases in BP, skinfold thickness (SFT) variables, and WHR in all of the CVD patients. Plasma Lp(a) was also significantly increased (p < 0.001), whereas the slight increase in the mean tHcy was not statistically significant. Positive significant correlations were found between systolic BP, triceps, SFT, and percentage body fat (p < 0.01), whereas significant correlations were found between some body composition variables, tHcy, and systolic BP (p < 0.05). Our findings provide supportive evidence for altered plasma Lp(a) concentration in addition to some other traditional CVD risk factors in Nigerians. The role of homocysteine is not well defined.


2020 ◽  
Vol 110 (5) ◽  
pp. 696-703
Author(s):  
Gabriel S. Tajeu ◽  
Monika M. Safford ◽  
George Howard ◽  
Virginia J. Howard ◽  
Ligong Chen ◽  
...  

Objectives. To determine factors that explain the higher Black:White cardiovascular disease (CVD) mortality rates among US adults. Methods. We analyzed data from the Reasons for Geographic and Racial Differences in Stroke study from 2003 to 2017 to estimate Black:White hazard ratios (HRs) for CVD mortality within subgroups younger than 65 years and aged 65 years or older. Results. Among 29 054 participants, 41.0% who were Black and 54.9% who were women, 1549 CVD deaths occurred. Among participants younger than 65 years, the demographic-adjusted Black:White CVD mortality HR was 2.23 (95% confidence interval [CI] = 1.87, 2.65) and 1.21 (95% CI = 1.00, 1.47) after full adjustment. Among participants aged 65 years or older, the demographic-adjusted Black:White CVD mortality HR was 1.58 (95% CI = 1.39, 1.79) and 1.12 (95% CI = 0.97, 1.29) after full adjustment. When we used mediation analysis, socioeconomic status explained 21.2% (95% CI = 13.6%, 31.4%) and 38.0% (95% CI = 20.9%, 61.7%) of the Black:White CVD mortality risk difference among participants younger than 65 years and aged 65 years or older, respectively. CVD risk factors explained 56.6% (95% CI = 42.0%, 77.2%) and 41.3% (95% CI = 22.9%, 65.3%) of the Black:White CVD mortality difference for participants younger than 65 years and aged 65 years or older, respectively. Conclusions. The higher Black:White CVD mortality risk is primarily explained by racial differences in socioeconomic status and CVD risk factors.


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