Framingham Risk Score Category Research Articles

Estimated pulse wave velocity added additional prognostic information in general population: Evidence from National Health and Nutrition Examination Survey (NHANES) 1999–2018

BackgroundAs an indicator of arterial stiffness, there is controversy over whether estimated pulse wave velocity (ePWV) add additional prognostic information other than cardiovascular risk factors or traditional risk estimation model in general population. MethodsData from National Health and Nutrition Examination Survey in 1999–2018 was analyzed. Cardiovascular risk factors were collected and Framingham Risk Score (FRS) was calculated. Using all-cause and cardiovascular mortality as outcomes, Cox and restricted cubic spline (RCS) analysis was performed. Receiver operator characteristic (ROC) curves, Harrell's C-statistic and net reclassification index (NRI) analysis were used to assess whether ePWV adds additional predictive value. ResultsThe association between ePWV and outcomes was independent of cardiovascular risk factors (HR = 1.23 [95%CI 1.23–1.50] per m/s for all-cause mortality, and 1.52 [1.30–1.78] for cardiovascular mortality) and FRS (1.22 [1.12–1.32] for all-cause mortality, and 1.32 [1.10–1.59] for cardiovascular mortality). Except for ePWV and all-cause mortality adjusted by FRS, a liner association was found between ePWV and outcomes. For predictive value, the area under ROC and C-index of the model added with ePWV was higher than the one with FRS or risk factors alone (P < 0.01). The elevated ePWV upgraded 1338456 subjects from high-intermediate to high FRS category, and NRI was 3.61 % and 2.62 % for all-cause and cardiovascular deaths, respectively (all P < 0.001). ConclusionsIn general population, the present study demonstrated the association between ePWV and all-cause, cardiovascular mortality is independent of cardiovascular risk factors and traditional risk estimated model. ePWV also added additional information to them in predicting clinical outcomes.

Normal Values for Myocardial Work Indices Derived From Pressure-Strain Loop Analyses: From the CCHS.

Pressure-strain loop analyses is a noninvasive technique capable of evaluating myocardial work. Reference values are needed to benchmark these myocardial work indices for clinical practice. Healthy participants from a general population study were used to establish reference values for global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) measured by pressure-strain loop analyses. The relation to age and sex was examined. We furthermore examined the proportion of abnormal work indices according to low, intermediate, and high cardiovascular risk by the Framingham risk score. The healthy sample consisted of 1827 participants (median age, 45 years; 39% men). Lower reference values were GWI, 1576 mm Hg%; GCW, 1708 mm Hg%; and GWE, 93.0% and upper reference value for GWW was 159 mm Hg%. Women exhibited significantly higher GWI, GCW, and GWW and lower GWE. Sex significantly modified the association between all indices and age (P for interaction: 0.001 for GWI, 0.009 for GCW, 0.003 for GWW, and 0.009 for GWE). For men, only GCW increased with age, whereas the other indices did not change with age. For women, GCW increased linearly with increasing age, whereas GWI, GWW, and GWE changed in a curvilinear fashion with age such that GWI increased in younger participants, GWW increased in elderly, and GWE declined concordantly. Abnormalities in myocardial work indices became more frequent with increasing Framingham risk score category (abnormal GWI: 2% versus 4% versus 5%, P=0.001; abnormal GCW: 2% versus 3% versus 4%, P=0.006; abnormal GWW: 3% versus 6% versus 11%, P<0.001; abnormal GWE: 3% versus 4% versus 11%, P<0.001). Myocardial work indices differ between sexes and change with age in a sex-dependent manner. Accordingly, we established age- and sex-specific reference values from a general population sample. Abnormal work indices become more frequent with higher clinical risk. URL: https://www. gov; Unique identifier: NCT02993172.

Does Adding Adverse Pregnancy Outcomes Improve the Framingham Cardiovascular Risk Score in Women? Data from the Tehran Lipid and Glucose Study.

BackgroundLimited and conflicting evidence is available regarding the predictive value of adding adverse pregnancy outcomes (APOs) to established cardiovascular disease (CVD) risk factors. Hence, the objective of this study was to determine whether adding APOs to the Framingham risk score improves the prediction of CVD events in women.Methods and ResultsOut of 5413 women who participated in the Tehran Lipid and Glucose Study, 4013 women met the eligibility criteria included for the present study. The exposure and the outcome variables were collected based on the standard protocol. Cox proportional hazard model was used to evaluate the association of APOs and CVDs. The variant of C‐statistic for survivals and reclassification of subjects into Framingham risk score categories after adding APOs was reported. Out of the 4013 eligible subjects, a total of 1484 (36.98%) women reported 1 APO, while 395 (9.84%) of the cases reported multiple APOs. Univariate proportional hazard Cox models showed the significant relations between CVD events and APOs. The enhanced model had a higher C‐statistic indicating more acceptable discrimination as well as a slight improvement in discrimination (C‐statistic differences: 0.0053). Moreover, we observed a greater risk of experiencing a CVD event in women with a history of multiple APOs compared with cases with only 1 APO (1 APO: hazard ratio [HR] = 1.22; 2 APOs: HR; 1.94; ≥3 APOs: HR = 2.48).ConclusionsBeyond the established risk factors, re‐estimated CVDs risk by adding APOs to the Framingham risk score may improve the accurate risk estimation of CVD. Further observational studies are needed to confirm our findings.

Adding Estimated Cardiorespiratory Fitness to the Framingham Risk Score and Mortality Risk in a Korean Population-Based Cohort Study.

Background: The added value of non-exercise-based estimation of cardiorespiratory fitness (eCRF) to cardiovascular disease (CVD) risk factors for mortality risk has not been examined in Korean populations. Methods: This population-based prospective cohort study examined the relationship of the 10-year Framingham risk score (FRS) for CVD risk and eCRF with all-cause and CVD mortality in a representative sample of Korean adults aged 30 years and older. Data regarding a total of 38,350 participants (16,505 men/21,845 women) were obtained from the 2007–2015 Korea National Health and Nutrition Examination Survey (KNHANES). All-cause and CVD mortality were the main outcomes. The 10-year FRS point sum and eCRF level were the main exposures. Results: All-cause and CVD mortality was positively correlated with the 10-year FRS point summation and inversely correlated with eCRF level in this study population. The protective of high eCRF against all-cause and CVD mortality was more prominent in the middle and high FRS category than in the low FRS category. Notably, the FRS plus eCRF model has better predictor power for estimating mortality risk compared to the FRS only model. Conclusions: The current findings indicate that eCRF can be used as an alternative to objectively measured CRF for mortality risk prediction.

Coronary artery plaque progression and cardiovascular risk scores in men with and without HIV-infection.

The aim of this study was to assess the association of cardiovascular disease (CVD) risk scores and coronary artery plaque (CAP) progression in HIV-infected participants. We studied men with and without HIV-infection enrolled in the Multicenter AIDS Cohort Study (MACS) CVD study. CAP at baseline and follow-up was assessed with cardiac computed tomography angiography (CCTA). We examined the association between baseline risk scores including pooled cohort equation (PCE), Framingham risk score (FRS), and Data collect of Adverse effects of anti-HIV drugs equation (D:A:D) and CAP progression. We studied 495 men (211 HIV-uninfected, 284 HIV-infected). The adjusted odds ratio (aOR) of total plaque volume (TPV) and noncalcified plaque volume (NCPV) progression in the highest relative to lowest tertile was 9.4 [95% confidence interval (95% CI) 2.4-12.1, P < 0.001)] and 7.7 (95% CI 3.1-19.1, P < 0.001) times greater, respectively, among HIV-uninfected men in the PCE atherosclerotic cardiovascular disease (ASCVD) high vs. low-risk category. Among HIV-infected men, the association for TPV and NCPV progression for the same PCE risk categories, odds ratio (OR) 2.8 (95% CI 1.4-5.8, P < 0.01) and OR 2.4 (95% CI 1.2-4.8, P < 0.05), respectively (P values for interaction by HIV = 0.02 and 0.08, respectively). Similar results were seen for the FRS risk scores. Among HIV-uninfected men, PCE high risk category identified the highest proportion of men with plaque progression in the highest tertile, although in HIV-infected men, high-risk category by D:A:D identified the greatest percentage of men with plaque progression albeit with lower specificity than FRS and PCE. PCE and FRS categories predict CAP progression better in HIV-uninfected than in HIV-infected men. Improved CVD risk scores are needed to identify high-risk HIV-infected men for more aggressive CVD risk prevention strategies.

Pictorial information about subclinical atherosclerosis reduces the CVD risk: Results from the VIPVIZA RCT

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Region Västerbotten and the Swedish Research Council Background The VIPVIZA trial has previously shown beneficial effects on cardiovascular disease (CVD) risk scores 1 year after sending pictorial information of carotid ultrasound imaging (Picture 1) to individuals and their physicians Purpose To investigate whether the beneficial effects on CVD-risk observed at 1-year were sustained over three years Methods VIPVIZA is a pragmatic prospective open-label randomized controlled trial with blinded evaluators performed within a CVD prevention programme integrated in the regular primary health care in Västerbotten County, Sweden. Individuals aged 40, 50 or 60 years old with one CVD risk factor were enrolled and randomised 1:1 to intervention (n = 1749, pictorial information about subclinical atherosclerosis provided to participants and physicians, Picture 1) or control group(n = 1783, no information to participants or physicians). Intervention participants also recieved a follow-up phone call and the corresponding physicians written guideline-based information about the clinical significance of carotid ultrasound results. Participants were examined at baseline (2013-2016), after one and at three years Results A significant beneficial effect on cardiovascular risk was observed at the 3-year follow-up; Framingham Risk Score (FRS) was 13.38 for the intervention group and 14.08 for the control group(p = 0.047) and SCORE was 1.69 vs. 1.82(p = 0.022) respectively. The 3-year results adjusted for sex and educational level showed significant differences between the intervention and control group in FRS, SCORE, P-Total-Cholesterol, P-LDL-Cholesterol and waist circumference in favour of the intervention group. Analysis by sex showed difference in differences(DID) in FRS for men -1.19(95% CI -2.01 to -0.37) and -0.50(95% CI -0.93 to -0.07) for women and in SCORE for men -0.20(95% CI -0.33 to -0.06) and -0.08 (95% CI -0.13 to -0.04) for women, between the two groups over 3 years. Similarly, there were significant differences in DID in all educational groups. Further stratification by baseline FRS and SCORE risk category, showed a beneficial pattern of the intervention in all risk groups, however the DID at the 3-year follow-up was statistically significant only in the intermediate risk group for both FRS -1.34(95% CI -2.13 to -0.56) and SCORE -0.19(95% CI -0.32 to -0.05) Conclusions This study provides evidence of sustained effects over three years of pictorial information of subclinical carotid atherosclerosis on the reduction of cardiovascular risk regardless of sex and educational level. Importantly, a statistically significant intervention effect was seen in the intermediate risk group, where the majority of CVD events occur. Visualization of subclinical atherosclerosis may be one way to approach individuals at intermediate risk of CVD, a group where sufficient prevention is often overlooked. However, further studies are needed to investigate the intervention effect on hard end points as CVD-events and death. Abstract Figure. Picture 1

Cardiovascular Risk Factors Among Patients Infected with COVID-19 in Saudi Arabia.

BackgroundCoronavirus disease (COVID-19) is a global pandemic with more than 60 million cases worldwide and over 1.5 million deaths by March 2021. Its outbreak has caused a huge burden on healthcare systems all over the world. Several studies in the medical literature have suggested that patients with underlying cardiovascular disease (CVD) are at higher risk for developing severe symptoms, poor prognosis, and high mortality rates. The aim of this study was to assess the prevalence of CVD risk factors among COVID-19 patients based on the Framingham risk score (FRS), and to evaluate the association of CVD risk factors with clinical outcomes.Patients and MethodsIn this retrospective cross-sectional study, we identified 264 confirmed cases with COVID‐19 at King Saud University Medical City in Riyadh, Saudi Arabia. Patients aged 18–80 years were included, and their electronic records were reviewed. They were classified into low, intermediate, and high risk of CVD according to FRS classification.ResultsTwo-hundred-six patients (67% male) were included in this study. The mean age was 55.3 ± 15.1 years. Most patients had comorbidities: the most common were hypertension (48.1%), diabetes (45.1%), and ischemic heart disease (11.2%). More than half required intensive care admission, and 58 (28.2%) patients died. Pneumonia was the most frequently observed complication (85%), followed by mechanical ventilation (28.3%) and acute kidney injury (27.7%). Age, male gender, hypertension, and diabetes mellitus showed significant differences between FRS categories, and were associated with intermediate and high-risk groups of FRS (p < 0.05). Pneumonia and length of stay were associated with the Intermediate risk group of FRS.ConclusionCardiovascular disease risk factors are prevalent in Saudi patients infected with COVID-19. FRS could be a useful tool to identify CVD risk factors among COVID-19 patients and predict a complicated course.

Non-alcoholic fatty liver disease (NAFLD) and the cardiovascular disease (CVD) risk categories in primary care: is there an association?

BackgroundNon-alcoholic fatty liver disease (NAFLD) is an emerging novel cardiovascular disease (CVD) risk factor. It’s prevalence is increasing globally. However, there is paucity in the evidence showing the association between NAFLD and CVD risk in primary care setting. Therefore, the objectives of this study were to determine the prevalence and factors associated with NAFLD among patients with ≥1 risk factor for NAFLD or CVD attending primary care clinics.MethodologyA cross sectional study was conducted in two clinics at a university primary care centre. Patients aged ≥18 years with ≥1 risk factor for NAFLD or CVD were recruited. Participants with history of established liver disease or chronic alcohol use were excluded. Socio-demographics, clinical related data, anthropometric measurements and blood investigation results were recorded in a proforma. Diagnosis of NAFLD was made using abdominal ultrasound. The 10-year CVD risk was calculated using the general Framingham Risk Score (FRS). Multiple logistic regression (MLogR) was performed to identify independent factors associated with NAFLD.ResultsA total of 263 participants were recruited. The mean age was 52.3 ± 14.7 years old. Male and female were equally distributed. Majority of the participants were Malays (79.8%). The overall prevalence of NAFLD was 54.4% (95%CI 48,60%). Participants in the high FRS category have higher prevalence of NAFLD (65.5%), followed by those in the moderate category (55.4%) and the low category (46.3%), p = 0.025. From MLogR, independent factors associated with NAFLD were being employed (OR = 2.44, 95%CI 1.26,4.70, p = 0.008), obesity with BMI ≥27.5 (OR = 2.89, 95%CI 1.21,6.91, p = 0.017), elevated fasting glucose ≥5.6 mmol/L (OR = 2.79, 95%CI 1.44,5.43, p = 0.002), ALT ≥34 U/L (OR = 3.70, 95%CI 1.85,7.44, p < 0.001) and high FRS category (OR = 2.82, 95%CI 1.28,6.23, p = 0.010).ConclusionNAFLD is highly prevalent among patients with ≥1 risk factor for NAFLD or CVD in these primary care clinics. Patients who were obese, have elevated fasting glucose, elevated ALT and in the high FRS category were more likely to have NAFLD. This study underscores the importance of targeted screening for NAFLD in those with risk factors in primary care. Aggressive intervention must be executed in those with NAFLD in order to reduce CVD complications and risk of progression.

Value of Carotid Ultrasound in Cardiovascular Risk Stratification in Patients With Psoriatic Disease.

This study aimed to assess whether subclinical atherosclerosis, as evaluated by carotid ultrasound, could predict incident cardiovascular events (CVEs) in patients with psoriatic disease (PsD) and determine whether incorporation of imaging data could improve CV risk prediction by the Framingham Risk Score (FRS). In this cohort analysis, patients with PsD underwent ultrasound assessment of the carotid arteries at baseline. The extent of atherosclerosis was assessed using carotid intima-media thickness (CIMT) and total plaque area (TPA). Incident CVEs (new or recurrent) that occurred following the ultrasound assessment were identified. The association between measures of carotid atherosclerosis and the risk of developing an incident CVE was evaluated using Cox proportional hazards models, with adjustment for the FRS. In total, 559 patients with PsD were assessed, of whom 23 had incident CVEs ascertained. The calculated rate of developing a first CVE during the study period was 1.11 events per 100 patient-years (95% confidence interval [95% CI] 0.74-1.67). When analyzed separately in Cox proportional hazards models that were controlled for the FRS, the TPA (hazard ratio [HR] 3.74, 95% CI 1.55-8.85; P = 0.003), mean CIMT (HR 1.21, 95% CI 1.03-1.42; P = 0.02), maximal CIMT (HR 1.11, 95% CI 1.01-1.22; P = 0.03), and high TPA category (HR 3.25, 95% CI 1.18-8.95; P = 0.02) were each predictive of incident CVEs in patients with PsD. The burden of carotid atherosclerosis is associated with an increased risk of developing future CVEs. Combining vascular imaging data with information on traditional CV risk factors could improve the accuracy of CV risk stratification in patients with PsD.

Cardiovascular Risk in HIV-Infected and Uninfected Postmenopausal Minority Women: Use of the Framingham Risk Score.

To characterize and compare cardiovascular disease (CVD) risk in HIV-infected and uninfected postmenopausal minority women using the Framingham Risk Score (FRS) as an assessment measure. A cross-sectional analysis was performed in 152 (109 HIV+, 43 HIV-) subjects from an existing study cohort of postmenopausal Hispanic and African American women. Data necessary to calculate FRS and menopause features were retrieved by retrospective chart review. Bivariate statistics was used to compare CVD risk factors. Multivariable linear regression was used to determine factors associated with FRS in HIV-infected women. The HIV-infected group was younger, less obese, and with lower rates of diabetes versus controls. In a subset of age-matched participants, median FRS did not differ between groups (14.6 [IQR = 9.1, 21.6] vs. 15.5 [IQR = 12.3, 22.1]; p = 0.73). Fourteen percent of HIV-infected women meeting criteria for the low-risk FRS category (<10%) had a history of CVD, a similar rate as controls. HIV-infected women at intermediate/high CVD risk had higher rates of surgical menopause. According to 2013 clinical guidelines, more than half of HIV-infected women not prescribed statin therapy (52%) were eligible for treatment; however, statin therapy was similarly under-prescribed in uninfected women. In this study, CVD risk as assessed by the FRS was not significantly different by HIV status. Performance of the FRS may be compromised in postmenopausal HIV-infected minority women. HIV-infected and uninfected women may be undertreated with statin therapy. Large longitudinal cohorts and inclusion of subclinical measures of CVD are necessary to better characterize risk.

Association between liver fibrosis and coronary heart disease risk in patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as the most common cause of chronic liver disease worldwide. It has been shown that NAFLD in adults is associated with increased risk of coronary heart disease (CHD). Because of the limitations of liver biopsy, noninvasive scoring indexes such as the NAFLD fibrosis score (NFS) were developed. The Framingham risk score (FRS) provides an estimate of CHD risk. In our study we aimed to investigate whether the severity of liver fibrosis estimated with the NFS is associated with a higher risk of CHD among individuals with ultrasonography-diagnosed NAFLD. A total of 155 patients and controls (81 patients with NAFLD and 74 controls) with ages ranging from 18 to 70 years were enrolled in this cross-sectional prospective study. Demographic, anthropometric, clinical, and laboratory data were obtained from each individual. The NAFLD patients were divided into subgroups on the basis of the severity of fatty liver. The FRS and NFS were adopted to predict the risk of CHD and the severity of hepatic fibrosis. In our study, we found that the FRS was higher in NAFLD patients than in controls (P<0.05). According to the FRS category, NFSs were higher in the intermediate/high probability CHD risk group in NAFLD (P<0.05). In multiple models, only age, sex, cholesterol, and HDL were independently associated with intermediate/high CHD risk (P<0.05). We also found a positive correlation between the NFS and the FRS (r=0.373, P<0.001). The optimum NFS cutoff point for identifying intermediate/high CHD risk in NAFLD patients was -2.1284, with a sensitivity and specificity of 95.20 and 48.30%, respectively. The predictive performance of the NFS in the determination of intermediate/high CHD risk in NAFLD patients was found to be 72% based on the area under the curve value. The FRS is associated with the NFS in NAFLD. The assessment of liver fibrosis may be useful for the risk stratification of CHD in the absence of liver biopsy in clinical practice.

Role of simultaneous carotid ultrasound in patients undergoing stress echocardiography for assessment of chest pain with no previous history of coronary artery disease

We prospectively explored prevalence of carotid disease (CD), its independent association with coronary artery disease (CAD) and outcome as well as potential impact on management, in patients undergoing stress echocardiography (SE) for new onset chest pain without known CAD. Accordingly, 591 consecutive patients referred for SE underwent carotid ultrasound. Carotid disease was defined as carotid intima-media thickness (C-IMT) >75th percentile for age and sex and/or presence of plaque. Myocardial ischemia was demonstrated in only a minority (11%), but there was a high prevalence of CD (70%). Incidence of CD was similar in patients with and without ischemia (76% versus 69%, P = .26). Carotid data led to reclassification of Framingham risk score categories in 65% of patients as well as more than a third of negative SE patients potentially benefitting from primary prevention therapy. Of the 83 patients undergoing coronary arteriography, 59 (71%) demonstrated coronary atherosclerosis (any atheroma) and 33 (40%) CAD. Positive predictive value of SE for CAD was 56%, but presence of carotid plaque improved it to 70%. Although both CD and plaque showed association with CAD and revascularization, after adjustment for conventional risk factors, only carotid plaque maintained significant association (P = .024 and P = .023, respectively). There is significantly higher prevalence of CD compared with myocardial ischemia in patients undergoing SE and carotid ultrasound for suspected CAD. This can lead to significant Framingham risk score reclassification with important primary prevention implications. Carotid plaque is superior to clinical assessment for the prediction of CAD and improves positive predictive value of SE for CAD in these patients.

Abstract P320: Discordance of Framingham Risk Score and Reynolds Risk Score to Global Vascular Risk Score: Results from the Hispanic Community Health Study/Study of Latinos

Introduction: The Framingham Risk Score (FRS) is a coronary heart disease (CHD) risk model established using an ethnically homogeneous population that predicts 10-year hard CHD events, myocardial infarction (MI) and coronary death. The Reynolds Risk Score (RRS) and Global Vascular Risk Score (GVRS) are validated CHD risk models that, in addition to hard CHD events, predict stroke and other CHD outcomes. In addition to major CHD risk factors, RRS adds systemic inflammation and family history of MI as GVRS adds behavioral and anthropometric measures. This study aims to compare agreement of RRS and GVRS with FRS among Hispanic/Latino adults and to describe discordance in RRS and GVRS with FRS categories, by socio-demographic characteristics. Methods: HCHS/SOL is a population-based cohort study of Hispanics/Latinos in four US communities. The analytic sample includes 6,058 non-diabetic participants 45-74 years of age with no past history of CHD and stroke who underwent comprehensive baseline examination. 10-year hard CHD risk score was calculated; participants were categorized as low (&lt;10%), moderate (10-&lt;20%), and high (≥20%) risk. Kappa scores were calculated to compare agreement of RRS and GVRS with FRS. Socio-demographic characteristics of concordance and discordance were characterized overall; multinomial logistic regression models was used to examine age-sex-adjusted likelihood of in discordance by these factors. Results: Mean age of the participants was 55 (SE=0.15) years, 54.3% were women, 41% had family history of CHD, and 90% were foreign born. Overall, 4,805 (74%) had low FRS, 1,143 (24%) had moderate FRS, and 110 (2%) had high FRS. There was poor agreement between RRS and FRS (Kappa=0.16, P&lt;0.01) and fair agreement between GVRS and FRS (Kappa=0.36, P&lt;0.01). In age-sex-adjusted analyses, RRS and GVRS were both more likely to classify persons of moderate and high risk who are between the ages of 60-74; GVRS classified more moderate and high risk women than the FRS. RRS and GVRS discordance with FRS was not associated with nativity and length of time in US. Conclusion: Significant discordance was observed between RRS and GVRS compared to FRS. Among Hispanic/Latino adults, use of RRS or GVRS may be more inclusive in classifying older age adults and women at high 10-year CHD risk.

The percentage flow-mediated dilation index: A large-sample investigation of its appropriateness, potential for bias and causal nexus in vascular medicine

The percentage flow-mediated dilation index (FMD%) scales the increase in arterial diameter (Ddiff) as a constant proportion of baseline artery diameter (Dbase). We have demonstrated, albeit with small samples, that the scaling properties of FMD% can lead to biased inferences on endothelial dysfunction. Therefore, we aimed to investigate the underlying rationale and potential bias of FMD% using a selection of new examples from the large (n = 3499) and diverse Multi-Ethnic Study of Atherosclerosis (MESA). In this dataset, we found that smaller values of Ddiff are associated with larger values of Dbase, which contradicts the scaling properties of FMD%. Consequently, FMD% 'over-scales' and naturally generates an even stronger negative correlation between itself and Dbase. Using a data simulation, we show that this FMD%-Dbase correlation can be a statistical artefact due to inappropriate scaling. The new examples we present from MESA indicate that FMD% biases the differences in flow-mediated response between men and women, Framingham risk score categories, and diseased and healthy people. We demonstrate how FMD%, as an exposure for predicting cardiovascular disease, is confounded by its dependency on Dbase, which itself could be clinically important. This critical review, incorporating an allometric analysis of a large dataset, suggests that the FMD% index has a less-than-clear rationale, can itself generate the Dbase-dependency problem, provides biased estimates of differences in the flow-mediated response, complicates the interpretation of the flow-mediated protocol and clouds the causal pathway to vascular disease. These interpretative problems can be resolved by applying accepted allometric principles to the flow-mediated response.

Plasma Monocyte Chemoattractant Protein-1 and Tumor Necrosis Factor-α Levels Predict the Presence of Coronary Artery Calcium in HIV-Infected Individuals Independent of Traditional Cardiovascular Risk Factors

Coronary artery calcium (CAC) is a validated subclinical measure of atherosclerosis. Studies in the general population have linked blood inflammatory biomarkers including monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor (TNF)-α with the burden of CAC, but this relationship is often lost following correction for traditional cardiovascular risk factors. We assessed the relationship of various biomarkers to CAC, specifically in HIV-infected individuals on potent antiretroviral therapy (ART). Analyses utilized entry data from participants in the Hawaii Aging with HIV-Cardiovascular (HAHC-CVD) study. Computerized tomography examinations for CAC were obtained locally and analyzed by a central reading center in blinded fashion. Plasma biomarkers were assessed by multiplexing using Milliplex Human Cardiovascular Disease panels. Among a cohort of 130 subjects [88% male, median (IQR) age of 51 (46-57) years, CD4 count of 492 (341-635) cells/mm(3), 86.9% with HIV RNA ≤50 copies/ml], CAC was present in 46.9% of subjects. In univariate analyses higher levels of log-transformed MCP-1 and TNF-α were associated with the presence of CAC (p<0.05). In multivariate logistic regression models, MCP-1 and TNF-α remained significant after adjustment for traditional cardiovascular (CVD) risk factors. Similar results were found when analyses were assessed by Framingham risk score categories or when restricted to subjects with plasma HIV RNA ≤50 copies/ml. In contrast to findings in the general population, higher MCP-1 and TNF-α predict the presence of CAC independent of traditional CVD risk factors in HIV-infected subjects fully suppressed on ART, suggesting that HIV-mediated immune activation may play a role in CVD risk.

ICEBERG. Intimal carotid evaluation before echocardiography reveals global vascular risk

Purpose: To determine the prevalence of carotid disease in patients presenting for a routine ECHO for non-vascular reasons and to correlate the findings with the patient's Framingham Risk Score (FRS). Methods: Males ≥40 years and females ≥50 years were eligible for participation. All gave signed informed consent to participate and completed a questionnaire regarding history of previous vascular disease, current Statin use, current smoking, diabetes, treatment for hypertension and family history of premature coronary disease. A recent lipid profile was obtained from their family doctor and if not available blood work was taken for fasting lipids. A limited carotid study was performed during the ECHO, 6 images were taken to include the Common Carotid Artery (CCA), carotid bulb and internal carotid artery bilaterally. Any carotid plaque or CCA IMT ≥1.20mm is indicative of increased cardiovascular risk according to the Canadian lipid guidelines. Results: 431 consecutive patients underwent a routine ECHO. 315 patients were excluded, mostly due to either current Statin use, or known vascular disease, (215), or age criteria (23 males <40yrs and 54 females <50 years). 116 patients had their FRS calculated and their carotid study completed. The prevalence of carotid disease according to FRS category (low, intermediate and high) is shown in the image below. ![Figure][1] FRS and prevalence of carotid disease. Conclusions: The overall prevalence of carotid disease was 58.6%. 81.2% of high FRS, 61.1% of intermediate FRS and 21.9% of low FRS. 66 of 68 patients with carotid disease had an LDL cholesterol >2.0mmol/l which is the Canadian guideline threshold for Statin therapy. 38 patients were classified as high FRS and 36 of these had an LDL cholesterol >2.0mmol/l, yet none were treated indicating that their FRS had likely never been previously calculated. [1]: pending:yes

Relationship between vascular age and classic cardiovascular risk factors and arterial stiffness

We aimed at establishing if the substitution of vascular age (VA) for chronological age (CA) causes a change in the Framingham Risk Score (FRS) categories. Sex differences in predictors of increased VA among cardiovascular (CV) risk factors and arterial stiffness (AS) parameters were identifi ed. In 187 asymptomatic subjects with CV risk factors, classifi ed into 3 FRS categories the VA was derived from the nomograms of the carotid intima-media thickness. Two groups: 1 - subjects whose VA has exceeded CA for at least 5 years and 2 - others were established. Carotid AS parameters were obtained from echo-tracking. Substitution of VA for CA changed the FRS category into the higher one in 11.8% of subjects. Diabetes mellitus (DM) was the predictor of increased VA in both sexes, while metabolic syndrome (MS) only in women. The cut-off values of AS parameters that allow for prediction of increased VA were determined from the ROC-curve analysis - in men: b > 7.3, Ep > 103 kPa, AC < 0.61 mm2/kPa after adjustment for DM, BMI > 29.1 kg/m2, WHR > 0.85 and CA > 51 years; in women: b > 9.6, Ep > 126 kPa, AC < 0.75 mm2/kPa, PWV-b > 7.4 m/s after adjustment for DM, BMI > 25.8 kg/m2, WHR > 0.80 and CA > 60 years. The substitution of VA for CA may increase the FRS category. Sex differences in predictors of increased VA were identifi ed. AS parameters proved to be predictors of increased VA besides the classic risk factors.

Hypertension prevalence and Framingham risk score stratification in a large HIV-positive cohort in Uganda

To report the prevalence of hypertension and projected 10-year absolute risk of acute cardiovascular disease in a large prospectively followed cohort of HIV-positive youth and adults beginning antiretroviral therapy in sub-Saharan Africa. HIV-positive individuals seeking HIV treatment, ages 13 years and older, were assessed for repeated blood pressure measurements over the first year following initiation of antiretroviral therapy, including serum total cholesterol, high-density lipoprotein, CD4 cell count and related clinical and laboratory measurements. Outcomes include hypertension, defined according to the 7th Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure categories, and Framingham Risk Score based 10-year cardiovascular disease risk estimates. Five thousand, five hundred and sixty-three patients had at least two blood pressure measurements on at least two separate occasions during the first year of antiretroviral therapy [median age of therapy initiation 34, first and third quartile (Q1-Q3) 28-40 years, 1841 (33.1%) men, baseline CD4 cell count 161 cells/μl (Q1-Q3 72-231 cells/μl]. Hypertension was diagnosed in 1551 patients [27.9%, 95% confidence interval (CI) 26.7- 29.1] including 786 (14.1%, 95% CI 13.2-15.1) who met criteria for stage 2 hypertension. The age-standardized prevalence for Ugandans aged 13 or more was 24.8% (95% CI 23.8-26.1). Among those with complete laboratory studies (n=1102), nearly all women were in the 10% or less 10-year Framingham Risk Score category, but 20% of men were at at least 10% or more long-term risk of acute cardiovascular disease. Efforts to combine HIV treatment with vascular disease risk factor prevention and management are urgently needed to address noncommunicable disease multimorbidity in HIV-positive persons in sub-Saharan Africa, particularly in men.

Coronary Artery Calcification Is an Independent Stroke Predictor in the General Population

Coronary artery calcification (CAC) is a noninvasive marker of plaque load that predicts myocardial infarcts in the general population. Herein, we investigated whether CAC predicts stroke events in addition to established risk factors that are part of the Framingham risk score. A total of 4180 subjects from the population-based Heinz Nixdorf Recall study (45-75 years of age; 47.1% men) without previous stroke, coronary heart disease, or myocardial infarction were evaluated for stroke events over 94.9 ± 19.4 months. Cox proportional hazards regressions were used to examine CAC as stroke predictor in addition to established vascular risk factors (age, sex, systolic blood pressure, low-density lipoprotein, high-density lipoprotein, diabetes mellitus, smoking, and atrial fibrillation). Ninety-two incident strokes occurred (82 ischemic, 10 hemorrhagic). Subjects suffering a stroke had significantly higher CAC values at baseline than the remaining subjects (median, 104.8[Q1;Q3, 14.0;482.2] vs 11.2[0;106.2]; P<0.001). In a multivariable Cox regression, log10(CAC+1) was an independent stroke predictor (hazards ratio, 1.52 [95% confidence interval, 1.19-1.92]; P=0.001) in addition to age (1.35 per 5 years [1.15-1.59]; P<0.001), systolic blood pressure (1.25 per 10 mm Hg [1.14-1.37]; P<0.001), and smoking (1.75 [1.07-2.87]; P=0.025). CAC predicted stroke in men and women, particularly in subjects <65 years of age and independent of atrial fibrillation. CAC discriminated stroke risk specifically in participants belonging to the low (<10%) and intermediate (10%-20%) Framingham risk score categories. CAC is an independent stroke predictor in addition to classical risk factors in subjects at low or intermediate vascular risk.

Abstract WP436: Plasma Inflammatory and Endothelial Activation Markers Are Associated with Carotid Intima Media Thickness in HIV-infected Individuals on Stable Antiretroviral Therapy

Background: Stroke risk is increased among HIV-infected persons on stable antiretroviral therapy (ART). Inflammatory cytokines and/or endothelial activation factors caused by HIV or other factors may confer risk beyond traditional cardiovascular (CVD) risk factors. Carotid intima-media thickness (cIMT) is associated with increased stroke risk. We assessed the hypothesis that soluble plasma inflammatory and endothelial activation biomarkers would be associated with cIMT independent of the Framingham Risk Score Category (FRSC), low: &lt;10%, medium: 10-20%, high: &gt;20% 10 year risk of CVD. Methods: Cross-sectional analyses were done in HIV+ subjects age &gt; 40 years on &gt; 6 months stable ART, without prevalent CVD. High-resolution B-mode ultrasound images of the right common carotid common artery (CCA) were obtained. CVD risk factors were collected and FRSC calculated. Plasma biomarkers were assayed by multiplex bead immunoanalysis. cIMT was log transformed to account for data non-normality. Univariate analyses were performed followed by sequential multivariate regression analyses for those showing significance with adjustment for age and FRSC. Results: Analyses were performed on 83 HIV+ subjects (n=72 males, median age 49 years, median CD4 Nadir 140, 72 with HIV RNA &lt; 50, 51 with low FRSC, 12 medium FRSC , 20 high FRSC). In univariate analyses, there were significant associations between the following biomarkers and log cIMT: sVCAM-1, CRP, SAA, IL-6, IL-8, and VEGF. There were no significant associations observed for sE-selectin, sICAM-1, MMP-9, MPO, tPAI-1, SAP, IL-1b, IL-10, TNF-α, MCP1, IFN-γ, and NT-proBNP. When age and FRSC were included in the model for biomarkers showing univariate significance, log CRP ( β=0.025; p=0.02), log SAA ( β=0.028; p=0.01), log IL-8 ( β=0.083; p=0.05), and VEGF ( β=0.0004; p=0.02) remained significantly associated with cIMT. Conclusions: In conclusion, the pro-inflammatory markers CRP, SAA, IL-8 and vascular activation marker, VEGF are associated with cIMT independent of age and traditional CVD risk factors in HIV-infected subjects on stable ART and suggest that inflammation and endothelial activation pathways involving these biomarkers may in part contribute to the excess stroke risk in HIV.