Clinical Cardiovascular Disease Risk Factors Research Articles

Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor

BackgroundPrader-Willi syndrome (PWS) is a rare genetic neurodevelopmental syndrome with highly increased risk of obesity and cardiovascular disease (CVD). Recent evidence suggests that inflammation is implicated in the pathogenesis. Here we investigated CVD related immune markers to shed light on pathogenetic mechanisms.MethodsWe performed a cross-sectional study with 22 participants with PWS and 22 healthy controls (HC), and compared levels of 21 inflammatory markers that reflect activity in different aspects of CVD related immune pathways and analyzed their association with clinical CVD risk factors.ResultsSerum levels of matrix metalloproteinase 9 (MMP-9) was (median (range)) 121 (182) ng/ml in PWS versus 44 (51) ng/ml in HC, p = 1 × 10-9), myeloperoxidase (MPO) was 183 (696) ng/ml versus 65 (180) ng/ml, p = 1 × 10-5) and macrophage inhibitory factor (MIF) was 46 (150) ng/ml versus 121 (163) ng/ml (p = 1 × 10-3), after adjusting for age and sex. Also other markers tended to be elevated (OPG, sIL2RA, CHI3L1, VEGF) but not significantly after Bonferroni correction (p > 0.002). As expected PWS had higher body mass index, waist circumference, leptin, C-reactive protein, glycosylated hemoglobin (HbA1c), VAI and cholesterol, but MMP-9, MPO and MIF remained significantly different in PWS after adjustment for these clinical CVD risk factors.ConclusionPWS had elevated levels of MMP-9 and MPO and of reduced levels of MIF, which were not secondary to comorbid CVD risk factors. This immune profile suggests enhanced monocyte/neutrophil activation, impaired macrophage inhibition with enhanced extracellular matrix remodeling. These findings warrant further studies targeting these immune pathways in PWS.

Ventricular-arterial coupling and cardiovascular risk among young adults: The African-PREDICT study.

Ventricular-arterial coupling (VAC) has independent diagnostic and prognostic value for cardiovascular (CV) risk stratification, but studies on its association with anthropometric and CV factors are sparse in young individuals without overt CV disease. We aim to provide descriptive data regarding VAC and its associations with CV risk factors in young adults without overt CV disease. For 631 (mean age, 24 ± 3 yr; 51% female) individuals, VAC was determined by carotid-femoral pulse wave velocity (PWV)/global longitudinal strain (GLS). Multivariable logistic and linear regression models were performed to explore the association between PWV/GLS and CV risk factors. A P-value < 0.05 was considered statistically significant. The mean PWV/GLS was 0.33 ± 0.07 m/s%. Higher ratios of PWV/GLS associated with older age, male sex, and a higher prevalence of CV risk factors (i.e., higher blood pressure, prevalent hypertension, higher waist circumference, active smoking, higher plasma triglycerides, lower high-density lipoprotein cholesterol, and an adverse urine albumin/creatinine ratio). Furthermore, higher PWV/GLS was associated with echocardiographic measures such as lower ejection fraction and higher left ventricle mass index. In expanded logistic regression models, higher ratios of PWV/GLS were significantly associated with the prevalence of active smoking [odds ratio (OR), 1.88; confidence interval (CI) 1.36-2.58, P < 0.001] and hypertension (OR 1.98; CI 1.40-2.80, P < 0.001). We demonstrated that worse VAC reflected by higher values of PWV/GLS are significantly associated with CV risk factors in young adults. The results suggest that PWV/GLS might serve as a tool to improve the profiling of cardiovascular risk in young adults.NEW & NOTEWORTHY Assessing VAC is especially useful in heart failure and valvular heart disease, but less is known about VAC in the pathophysiology of CV disease risk in younger individuals. In young individuals without overt CV disease, we showed descriptive data regarding VAC, determined by PWV/GLS ratio, and explored the associations of VAC with clinical CV disease risk factors. Worse VAC, reflected by higher values of PWV/GLS, associated with high blood pressure and smoking in young adults.

Abstract 10427: Association Between Blood Pressure Levels and Prevalence of Premature Atrial Contractions in Patients With Hypertension

Background: High blood pressure (BP) leads to left atrial functional and structural abnormalities, which is the substrate for atrial arrhythmias. We hypothesized that, among patients with hypertension, higher levels of systolic BP (SBP) would be associated with a higher prevalence of premature atrial contractions (PACs), the most common cardiac arrhythmia that has been associated with poor outcomes in the general populations. Methods: This analysis included 4,497 (mean age 62.1±13.2 years, 49.9% women, 48.9% Whites) participants with hypertension from the Third National Health and Nutrition Examination Survey who were free of clinical cardiovascular disease (CVD). Multivariable logistic regression analysis was used to examine the cross-sectional association between SBP and the prevalence of PACs ascertained from electrocardiograms (ECGs) read at a central ECG core. Multivariable Cox proportional hazard analysis was used to examine the association between baseline PACs and CVD mortality occurring during follow-up. Results: About 1.6% (n=74) of the participants had PACs at baseline. Patients with SBP &lt;140/&lt;90 mmHg had lower prevalence of PACs compared to those with SBP &gt; 140/≥90 mmHg (1.12% vs. 1.99%, p-value=0.019). Each 10 mmHg lower in SBP was associated with 11% lower odds of PACs in a multivariable logistic regression model adjusted for demographics, CVD risk factors, and major ECG abnormalities (OR (95%CI): 0.89 (0.78-1.02)). A total of 645 CVD deaths occurred during 14 years of follow-up. Presence (vs. absence) of PACs was associated with a 70% increased risk of CVD mortality in Cox models adjusted for demographics, CVD risk factors, and major ECG abnormalities (HR (95%CI): 1.70 (1.14-2.52)). Conclusions: Among patients with hypertension, presence of PACs is associated with an increased risk of CVD mortality, and lower levels of BP are associated with a lower prevalence of PACs. These findings highlight the potential role of intensive BP lowering in managing cardiac arrhythmias in hypertension patients.

Postprandial triglyceride levels rather than fat distribution may reflect early signs of disturbed fat metabolism in Iraqi immigrants

PurposePrevious studies have shown that at a similar body mass index, Middle Eastern immigrants are more insulin resistant and at higher risk for type 2 diabetes (T2D) than native Europeans. Insulin resistance is strongly associated with disturbed fat metabolism and cardiovascular disease (CVD). However, fat metabolism is poorly investigated comparing Middle Eastern and European ethnicities.MethodsThis observational study included 26 Iraqi and 16 Swedish-born men without T2D or clinical risk factors for CVD. An oral fat tolerance test (OFTT) was performed, where plasma triglycerides (p-TG) were measured for 6 h. mRNA expression and adipocyte size were measured in subcutaneous adipose tissue biopsies collected prior to OFTT, and magnetic resonance imaging was conducted to assess body fat distribution.ResultsThe median p-TG accumulation was higher and the clearance slower among Iraqis than Swedes. None of the groups reached their fasting p-TG (Iraqis 1.55 mmol/l; Swedes 0.95 mmol/l) after 6 h (Iraqis p-TG 3.10 mmol/l; Swedes p-TG 1.50 mmol/l). Adipocyte size, mRNA expression, and fat accumulation in the liver, muscle and abdomen were similar in both groups.ConclusionPostprandial p-TG levels rather than fat distribution may reflect early signs of disturbed fat metabolism in Iraqi immigrants without CVD risk factors.

Prevalence of Clinical Cardiovascular Disease Risk Factors Among HIV Infected Patients on Anti-Retroviral Treatment in a Tertiary Hospital in Ethiopia.

BackgroundAnti-retroviral treatment has improved mortality of human immunodeficiency virus (HIV) infected patients, which is offset by an increasing burden of cardiovascular diseases (CVD). Data regarding prevalence of cardiovascular disease risk factors in HIV infected patients in Ethiopia are very scarce. The aim of this study was to determine the prevalence of CVD risks and associated factors in patients with HIV.MethodsA cross-sectional study was conducted on 333 patients with HIV infection, using a modified World Health Organization’s stepwise approach to surveillance questionnaire. Anthropometric and blood pressure measurement was done along with biochemical studies. Cardiovascular risk was estimated using Framingham risk score. Multivariate logistic regression was used to examine the association between cardiovascular risks and associated factors, with a p-value of <0.05 considered statistically significant.ResultsThe mean age of the participants was 45 years, and 69.2% were females. Most (80.9%) of the participants had viral load below 50 copies/mL and the mean CD4 count was 579 cells/mm3. Dyslipidemia was the most common risk factor identified in 69.4%, followed by abnormal fasting blood glucose (≥100 mg/dL) in 36.8%. Hypertension was diagnosed in 23.8%, while 22.8% and 11.1% had metabolic syndrome and obesity, respectively. Framingham risk score was low in 95.9%. Male gender, increasing age, high body mass index and previous ART regimen being tenofovir disoproxil fumarate, lamivudine and nevirapine increased CVD risk factors.ConclusionTraditional cardiovascular risk factors were high in the population studied. There is a need to raise awareness about the risk factors, and patients should have timely follow-up and care.

0705 Association of high risk obstructive sleep apnea with atherosclerotic plaque, coronary stenosis and coronary artery calcium score in asymptomatic young and middle-aged adults in The Miami Heart (MiHeart) Study at Baptist Health South Florida

Abstract Introduction Obstructive Sleep Apnea (OSA) is associated with clinical cardiovascular disease (CVD). There are limited data evaluating association with subclinical CVD measured by cardiac computed tomography (CT). We hypothesized there would be significant association between high OSA risk and atherosclerotic plaque, coronary stenosis, and coronary artery calcium (CAC) score in Miami Heart Study cohort free of CVD. Methods Data from CVD free 2359 participants, age 40-65 years (May 2015-Sept 2018) from greater Miami were analyzed. Cardiac CT measured CAC, coronary plaque burden and stenosis. High OSA risk was defined as either OSA diagnosis and/or a high risk from Berlin questionnaire. Logistic regression examined association between high OSA risk (reference low OSA risk) and any plaque, coronary stenosis &amp;gt;50%, and CAC (&amp;gt; 0 and &amp;gt; 100 vs 0) in unadjusted models, and after accounting for age, sex, race/ethnicity (model 2), and BMI, diabetes, high cholesterol, and smoking (model 3). Results 800 (34%) participants had high OSA risk; were more likely to be male, Hispanic, with higher CVD risk factor burden compared to low OSA risk. High OSA risk had higher prevalence of any plaque (60% vs 44%), coronary stenosis ≥ 50% (8.3% vs 4.8%), CAC scores &amp;gt;0-99 (34% vs 26%), and CAC score ≥ 100 (16% vs 12%), compared to low OSA risk (all p &amp;lt; 0.05). High OSA risk was associated with higher odds of any plaque, coronary stenosis ≥ 50%, high-risk plaque features, CAC &amp;gt; 0 and CAC ≥ 100 in univariable models. When adjusting for age, sex and race/ethnicity, these patterns persisted, with 1.58 higher odds of any plaque (95% CI 1.31, 1.91), 1.54 higher odds of coronary stenosis ≥ 50% (95% CI 1.08, 2.20), 1.37 higher odds of having CAC &amp;gt; 0 (95% CI 1.13, 1.66). Associations became non-statistically significant when adjusting for CVD risk factors, except any plaque, which was independently associated after fully adjusted (OR 1.31 (1.05, 1.63). Conclusion Individuals with high risk for OSA, significantly prone for CVD risk factor, have higher likelihood for presence of any plaque, significant stenosis and CAC scores &amp;gt; 0, with these associations mostly mediated by CVD risk factors. Support (If Any) Baptist Health South Florida

Interleukin‐8 (IL‐8) as a Potential Mediator of an Association Between Trimethylamine N‐Oxide (TMAO) and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) among African‐Americans at Risk for Cardiovascular Disease

Trimethylamine N‐Oxide (TMAO) is a microbial metabolite derived from the hepatic‐gut axis and linked to inflammation and cardiovascular disease (CVD). Studies have shown that TMAO is linked to CVD and its risk factor hyperlipidemia by enhanced macrophage foam cell formation or alterations in reverse cholesterol transport. Other mechanisms have not been reported to date. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a largely hepatic expressed protein that blocks Low Density Lipoprotein (LDL) receptor recycling, leading to hyperlipidemia. The primary objective of this study was to investigate a potential relationship between TMAO and PCSK9 in order to explore a novel mechanism linking TMAO and CVD risk. We hypothesized that TMAO and PCSK9 would have a direct association among a sample of African American adults, a population at increased risk for CVD, and that this relationship would be mediated by inflammatory cytokines.African‐American adults at risk for CVD living in the Washington, DC area were recruited to participate in a cross‐sectional community‐based study that involved clinical examination and collection of fasting blood samples. Serum samples were analyzed for clinical CVD risk factors. Fasting levels of inflammatory cytokines (interleukin (IL)‐1 beta, tumor necrosis factor‐alpha, and interleukin‐8), TMAO, and PCSK9 were measured using Luminex and ELISA, respectively. Univariate and multivariate linear regression analyses and structural equation mediation analyses were conducted using STATA. All models were adjusted for body mass index (BMI) and atherosclerotic CVD risk score (ASCVD).The participant sample (n = 60) included a majority of self‐identified African‐American women (93.33%), who presented as obese (Mean BMI = 33). A significant association between TMAO and PCSK9 was identified in both unadjusted (β = 0.30, p = 0.02) and adjusted (β = 0.31, p =0.02) models. Both TMAO and PCSK9 were significantly associated with IL‐8 (TMAO: β = 0.45, p = 0.00; PCSK9: β = 0.23, p = 0.05) in adjusted models. Mediation analysis indicated that 34.77% of the relationship between TMAO and PCSK9 was explained by IL‐8 (Figure 1).Our findings indicate a potential PCSK9 involved pathway for TMAO and CVD risk. Furthermore, our results suggest this pathway is mediated by the inflammatory cytokine, IL‐8. Future studies may identify the role of dietary or stress‐related factors that could increase IL‐8 and potentially influence the TMAO‐PCKSK9 relationship.

Abstract 10173: Risk Factors of Cardiovascular Disease in Breast Cancer Patients

Introduction: Cardiovascular disease (CVD) events during cancer treatment can interfere with the delivery of curative therapy. In adult cancer survivors, CVD mortality is second only to cancer recurrence related mortality. We evaluated the demographic and clinical risk factors of CVD in breast cancer patients. Methods: A retrospective cohort study was conducted at Kaiser Permanente Southern California (KPSC) health system. We identified adult members (18+) diagnosed with primary breast cancer from 01/2000-12/2019 using the KPSC cancer registry. We only included patient who had at least one year of continuous health plan enrollment prior to their cancer diagnosis to determine risk factors status and to ensure they did not have any history of CVD (defined as cardiac arrest, cardiomyopathy, congestive heart failure, coronary atherosclerosis, heart valve disorders, myocardial infarction, ventricular fibrillation, dysrhythmias or stroke) prior to their cancer diagnosis. We evaluated the association of age at cancer diagnosis; race; ethnicity; obesity; cancer stage; and history of depression, drug abuse, renal failure, liver disease, lipid disorder, diabetes and hypertension using a proportional hazard model. All patients were followed from their cancer diagnosis to the earliest date of CVD (failure event) diagnosis or death or health plan disenrollment or end of study (12/2020). Results: In the cohort of 36,840 patients (Table 1), 11,993 (33%) had a CVD diagnosis during follow-up (average follow-up 5.3 years). The hazard rate of CVD increased significantly with age. Distant metastatic disease was associated with 7-fold higher CVD hazard as compared to in-situ cancer. Most other clinical factors significantly increased the hazard rate (Table 1). Conclusions: In breast cancer patients naïve to CVD disease prior to cancer diagnosis, the hazard rate of CVD post cancer diagnosis is significantly higher in older individuals and those with metastatic disease.

Abstract 010: Application Of A Lifestyle-based Score To Predict Cardiovascular Risk In African Americans: The Jackson Heart Study

Introduction: Cardiovascular disease (CVD) primordial prevention tools applicable to diverse populations are scarce. Hypothesis: We assessed the hypothesis that the Healthy Heart Score, a lifestyle-based tool to estimate CVD risk, will perform well in estimating CVD risk in an African American population. Methods: The Jackson Heart Study (JHS) is a prospective cohort, community-based study in Jackson, Mississippi that recruited participants between September 2000 and March 2004 (baseline), with a mean follow up of 12 years. A total of 5306 African American were recruited, 3041 individuals free of CVD at baseline were included for the current analysis. CVD incidence was defined as the first occurrence of fatal/non-fatal myocardial infarction (MI), stroke or fatal coronary heart disease (CHD). The Healthy Heart Score is a lifestyle-based CVD risk prediction model based on 9 components: body mass index (BMI), physical activity, cereal fiber, fruit and vegetables, red and processed meat, nuts, sugar and sweetened beverages and alcohol intake. Gender-specific beta coefficients from its derivation cohorts were used to assess the performance of the Healthy Heart Score. Model discrimination was assessed using Harrell′s C-Index for survival data and time dependent Area Under the Curve (AUC). Model calibration was evaluated through calibration plots. Results: A total of 189 CVD events occurred (111 in women and 78 in men, average age at baseline 53.1 (12.7) years). The Healthy Heart Score showed high-moderate discrimination for CVD events (C-statistic 0.75 (95% CI, 0.71-0.78)) but with little improvement over the age-only model. The time dependent AUC analysis showed similar results for CVD events and improved performance in the first year with the complete model (age only: AUC 0.76 (95% CI, 0.65-0.88) vs. Healthy Heart Score 0.78 (95% CI 0.68-0.89)). Both the age-only and Healthy Heart Score models had better performance in participants without diabetes at baseline. The Healthy Heart Score model showed good calibration. Conclusions and Relevance . In African Americans with a high prevalence of clinical CVD risk factors, the Hearty Heart Score does not improve prediction of mid-life CVD events beyond what is obtained by age alone.

Wales Inverse Care Law Programme - Design and Implementation of Routine Data Evaluation and Lessons Learned

IntroductionThe Inverse Care Law (ICL) programme in Wales was setup to tackle health inequalities. Eligible populations from deprived communities, at higher risk of cardiovascular disease (CVD) were invited to a health-check and offered appropriate lifestyle and clinical interventions.&#x0D; Objectives and ApproachEvaluation of this programme is vital to ensure that targeted interventions have been received by those most in need, including referrals to lifestyle services and support. The use of longitudinal population-scale routine-data required the development of an approach which was both efficient and cost effective. To achieve this, the Welsh Longitudinal General Practice (WLGP) data held in SAIL Databank was utilised. A programme-specific methodology was agreed by the programme-board and developed so that data collected from GP records prior, during and post health-check accurately identified the eligible population and allowed the effective assessment of lifestyle and clinical risk factors for CVD; poor diet, physical inactivity, smoking and high alcohol intake, so appropriate interventions could be offered.&#x0D; ResultsWe evaluated the programme from 2015 to 2019 in 70 GP’s across the participating Health-Boards, and identified 175,671 individuals eligible by the programme criteria. Substantial preliminary work has been carried out to ensure the specification of outcome measures are both clinically and epidemiologically accurate and relevant. The final report scheduled for release in August-2020, which will evaluate the impact of the programme.&#x0D; Conclusion / ImplicationsThis ambitious evaluation of a large-scale programme set in the community involving disparate systems and a range of stakeholders, has been both complex and challenging, requiring substantial effort to design and implement. We hope the outcomes and lessons learned from our experience will improve the design, implementation and evaluation of the programme and lead to improvements in services and the quality of life for people in Wales, and provide an exemplar for health care providers worldwide wishing to conduct similar programmes in the future.

Cardiovascular disease risk prediction for people with type 2 diabetes in a population-based cohort and in electronic health record data.

ObjectiveElectronic health records (EHRs) have become a common data source for clinical risk prediction, offering large sample sizes and frequently sampled metrics. There may be notable differences between hospital-based EHR and traditional cohort samples: EHR data often are not population-representative random samples, even for particular diseases, as they tend to be sicker with higher healthcare utilization, while cohort studies often sample healthier subjects who typically are more likely to participate. We investigate heterogeneities between EHR- and cohort-based inferences including incidence rates, risk factor identifications/quantifications, and absolute risks.Materials and methodsThis is a retrospective cohort study of older patients with type 2 diabetes using EHR from New York University Langone Health ambulatory care (NYULH-EHR, years 2009–2017) and from the Health and Retirement Survey (HRS, 1995–2014) to study subsequent cardiovascular disease (CVD) risks. We used the same eligibility criteria, outcome definitions, and demographic covariates/biomarkers in both datasets. We compared subsequent CVD incidence rates, hazard ratios (HRs) of risk factors, and discrimination/calibration performances of CVD risk scores.ResultsThe estimated subsequent total CVD incidence rate was 37.5 and 90.6 per 1000 person-years since T2DM onset in HRS and NYULH-EHR respectively. HR estimates were comparable between the datasets for most demographic covariates/biomarkers. Common CVD risk scores underestimated observed total CVD risks in NYULH-EHR.Discussion and conclusionEHR-estimated HRs of demographic and major clinical risk factors for CVD were mostly consistent with the estimates from a national cohort, despite high incidences and absolute risks of total CVD outcome in the EHR samples.

Abstract P201: Prospective Associations of Innate and Adaptive Immune Cell Subsets in Peripheral Blood With Incident Myocardial Infarction

Introduction: Activation of cell-mediated immunity promotes atherogenesis in animal models and correlates with advanced atherosclerosis and coronary syndromes in humans. Whether innate and adaptive immune cell subsets are risk factors for clinical cardiovascular disease (CVD) events is unknown. Hypothesis: Circulating proportions of pro-inflammatory (Th1, Th17), anti-inflammatory (Th2, T regulatory), and differentiated (naive, memory, and senescent) CD4 + T cells are risk factors for myocardial infarction (MI) and angina. We explored other cell types in secondary analyses. Methods: We performed a case-cohort study within the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS) (n=2,162). Case outcomes were incident MI and incident angina (n=869 total cases) compared to a cohort random sample (n=1,293). Immune cell phenotypes (n=34, including monocytes, T cells, and B cells) were measured by flow cytometry using cell samples cryopreserved at the MESA baseline and CHS Year 11 exams. Associations of immune cell phenotypes with MI and a composite outcome of incident MI or incident angina (MI-angina) were evaluated using Cox proportional hazards models, with sampling weights and CVD risk factor adjustment, over a median follow-up time of 9.3 years. We analyzed results separately in each cohort and in a combined-cohort meta-analysis. Based on previous findings, we specified seven CD4 + T cell populations as primary hypotheses (stated above). In Bonferroni-adjusted secondary analyses, we investigated associations of 27 additional cell phenotypes measured in the study. Results: In our primary hypotheses, the associations of Th1, Th2, T regulatory, naive, memory, and senescent CD4 + cells with incident MI were moderate and not statistically significant in either cohort individually or in combined-cohort analyses (hazards ratios ranging from 0.88 for naive cells (95% confidence interval (CI): 0.73, 1.06) to 1.15 for Th2 cells (95 CI: 0.96,1.38); all P-values &gt;0.05). Associations of these cells with the composite endpoint of incident MI-angina were also null (hazards ratios ranging from 0.90 (Th1 cells; 95% CI: 0.74, 1.11) to 1.11 (Th17 cells; 95% CI: 0.91, 1.37); all P-values &gt;0.10). In exploratory secondary analyses that investigated subsets of CD14 + monocytes, CD8 + T cells, and CD19 + B cells, no significant relationships with incident MI or MI-angina were observed. Conclusions: In a study of modest sample size, these results suggest that variation in the proportions of several lymphocyte and monocyte subsets measured in peripheral blood are only weakly, if at all, associated with incident MI or incident angina. Given the literature on the roles of cellular immunity in atherosclerosis, large prospective studies evaluating the relationships of immune cell subsets with the progression of atherosclerosis are warranted.

Early or Late Pregnancy Loss and Development of Clinical Cardiovascular Disease Risk Factors: A Prospective Cohort Study

(BJOG. 2019;126:33–42) Certain pregnancy complications, including preterm birth, preeclampsia and gestational hypertension, are female-specific risk factors for cardiovascular disease (CVD), the leading cause of death for both men and women. Pregnancy loss has been suggested as a possible risk factor for CVD. Although stillbirth and spontaneous abortion have been associated with an increased risk of stroke and ischemic heart disease, there is a lack of information regarding increased risk of CVD in women with a history of spontaneous pregnancy loss. This study aimed to assess the associations of pregnancy loss and risk of hypertension, type 2 diabetes (T2D), and hypercholesterolemia.

Collagen biomarkers are associated with decline in renal function independently of blood pressure and other cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis Study.

We studied associations of circulating collagen type I carboxy-terminal telopeptide (ICTP) and procollagen type III N-terminal propeptide (PIIINP) with long-term renal function decline. In the Multi-Ethnic Study of Atherosclerosis, we included 2492 participants initially aged 45-84 years and free of clinical cardiovascular disease (CVD), excluding people with estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m or urine albumin/creatinine (UAC) at least 30 mg/g. The primary outcome in median 9.4-year follow-up was renal function decline (≥30% decline in eGFR between any two exams or incident UAC ≥ 30 mg/g). The associations of baseline plasma ICTP and PIIINP with renal function decline were estimated using Poisson regression, adjusting for baseline variables race/ethnicity, sex, age, and continuous eGFR and UAC, with further adjustment for CVD risk factors and medications. Baseline serum ICTP was 3.27 ± 1.43 μg/l and PIIINP was 5.43 ± 1.85 μg/l. Mean baseline eGFR was 91.5 ± 18.4 ml/min per 1.73 m. Renal function decline occurred in 19.5% during 9.4-year follow-up. The renal function decline outcome was positively associated with serum ICTP and PIIINP: relative incidence density (95% confidence interval) per SD 1.22 (1.11-1.33) and 1.27 (1.16-1.40), respectively. Additional adjustment for other risk factors did not greatly alter findings. High collagen biomarker concentrations in serum were associated with future decline in renal function in people initially free of CVD and with normal eGFR, consistent with collagen production signaling renal decline. The continuous association observed for ICTP which, unlike PIIINP, is filtered by the kidney, may owe to its double status as a sensitive marker of glomerular function and collagen degradation.

Association of Insulin Dose, Cardiometabolic Risk Factors, and Cardiovascular Disease in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study.

OBJECTIVEThe Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated the beneficial effects of intensive therapy on atherosclerosis and clinical cardiovascular disease (CVD) outcomes. The current analyses evaluated the relationship between longitudinal changes in insulin dose and CVD risk factors and outcomes.RESEARCH DESIGN AND METHODSA total of 1,441 participants were randomly assigned to intensive or conventional diabetes therapy during the DCCT. After an average of 6.5 years of follow-up, 96% of the surviving cohort enrolled in the EDIC observational study, which included annual visits with detailed medical history, physical examination, and laboratory testing. CVD events were adjudicated by a review committee. Generalized linear mixed models and Cox proportional hazards regression models were used to assess the association between insulin dose and cardiometabolic risk factors and CVD risk, respectively, over a total of 30 years.RESULTSHigher insulin doses were significantly associated with a less favorable cardiometabolic risk profile (higher BMI, pulse rate, and triglycerides and lower HDL cholesterol) with the exception of lower diastolic blood pressure and lower LDL cholesterol. In a minimally adjusted model, a 0.1 unit/kg body wt/day increase in insulin dose was associated with a 6% increased risk of any CVD (95% CI 3, 9). However, the association with insulin dose was no longer significant after adjustment for other CVD risk factors.CONCLUSIONSDuring DCCT/EDIC, higher insulin doses were associated with adverse trends in several cardiometabolic risk factors, even after multivariable adjustment, but not with incident CVD outcomes.

Differences in statin utilization and lipid lowering by race, ethnicity, and HIV status in a real-world cohort of persons with human immunodeficiency virus and uninfected persons

Risks for cardiovascular diseases, including myocardial infarction and stroke, are elevated in people with HIV infection (PWH). However, no trials of statin utilization with clinical cardiovascular disease (CVD) end points have been completed in PWH, and there are sparse real-world data regarding statin use and lipid-lowering effectiveness. We therefore used a unique cohort of PWH and uninfected controls to evaluate (1) differences in statin types used for PWH versus uninfected persons; (2) lipid lowering achieved by statin use for PWH versus uninfected persons; and (3) racial and ethnic disparities in appropriate statin use among PWH and uninfected persons. We analyzed a cohort of 5,039 PWH and 10,011 uninfected demographically matched controls who received care at a large urban medical center between January 1, 2000, and May 17, 2017. Medication administration records, prescription data, and validated natural language processing algorithms were used to determine statin utilization. Statins were categorized by generic active ingredient name and intensity (high, moderate, or low). Lipid values collected in routine clinical care were available for analysis. The first set of analyses was restricted to PWH and uninfected matched controls taking statins and compared (1) differences in statin type and (2) difference in cholesterol levels after versus before statin initiation by HIV status. For the second set of analyses, we first used prevalent CVD risk factors to determine participants with statin indications and then determined how many of these participants were taking statins. We then compared statin utilization among persons with indications for statins by race/ethnic group for PWH and uninfected matched controls using multivariable-adjusted logistic regression. Among people prescribed statins, PWH were more likely than controls to have ever taken pravastatin (34.8% vs 12.3%, P < .001) or atorvastatin (72.2% vs 65.6%, P = .002) and less likely to have ever taken simvastatin (14.2% vs 39.5%, P < .001). Among PWH with indications for statin utilization, 55.7% of whites, 39.4% of blacks, and 45.8% of Hispanics were prescribed statins (P < .001). These differences in statin prescription by race/ethnicity remained significant after adjustment for demographics (including insurance status), cardiovascular risk factors, antiretroviral therapy use, HIV viremia, and CD4 count. These racial/ethnic disparities in statin utilization were less pronounced among uninfected persons. Among PWH with statin indication(s), blacks and Hispanics were less likely than whites to have been prescribed a statin. These racial/ethnic disparities were less pronounced among uninfected persons. There were significant differences in type of statin used for PWH compared to uninfected matched controls. Future efforts addressing disparities in CVD prevention among PWH are warranted.

Urinary 2,5-dicholorophenol and 2,4-dichlorophenol concentrations and prevalent disease among adults in the National Health and Nutrition Examination Survey (NHANES)

ObjectiveTo test cross-sectional associations between urinary concentrations of 2,5-dichlorophenol (2,5-DCP) and 2,4-dichlorophenol (2,4-DCP) with the prevalence of cardiovascular disease (CVD), cancer, lung disease, thyroid problems and liver conditions.MethodsLogistic regression was...

Early or late pregnancy loss and development of clinical cardiovascular disease risk factors: a prospective cohort study

To assess the association between the outcome of a woman's first pregnancy and risk of clinical cardiovascular disease risk factors. Prospective cohort study. Nurses' Health Study II. Multivariable-adjusted Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between first pregnancy outcome and hypertension, type 2 diabetes, and hypercholesterolemia. Hypertension, type 2 diabetes, and hypercholesterolemia. Compared to women who reported a singleton live first birth, women with early spontaneous abortion (<12 weeks) had a greater rate of type 2 diabetes (HR: 1.20; 95% CI: 1.07-1.34) and hypercholesterolemia (HR: 1.06; 95% CI: 1.02-1.10), and a marginally increased rate of hypertension (HR: 1.05, 95% CI: 1.00-1.11). Late spontaneous abortion (12-19 weeks) was associated with an increased rate of type 2 diabetes (HR: 1.38; 95% CI: 1.14-1.65), hypercholesterolemia (HR: 1.11; 95% CI: 1.03-1.19), and hypertension (HR: 1.15; 95% CI: 1.05-1.25). The rates of type 2 diabetes (HR: 1.45; 95% CI: 1.13-1.87) and hypertension (HR: 1.15; 95% CI: 1.01-1.30) were higher in women who delivered stillbirth. In contrast, women whose first pregnancy ended in an induced abortion had lower rates of hypertension (HR: 0.87; 95% CI: 0.84-0.91) and type 2 diabetes (HR: 0.89; 95% CI: 0.79-0.99) than women with a singleton live birth. Several types of pregnancy loss were associated with an increased rate of hypertension, type 2 diabetes, and hypercholesterolemia, which may provide novel insight into the pathways through which pregnancy outcomes and CVD are linked. Pregnancy loss is associated with later maternal risk of hypertension, type 2 diabetes, and hypercholesterolemia.

Preterm Delivery and Maternal Cardiovascular Disease Risk Factors: The Nurses' Health Study II.

Background: Preterm delivery has been linked to future maternal cardiovascular disease (CVD); however, research investigating clinical CVD risk factors is limited. We evaluated whether women who have delivered an infant preterm are at higher risk of developing CVD risk factors after adjustment for prepregnancy confounders. Materials and Methods: We examined the association between preterm delivery and incident chronic hypertension, type 2 diabetes mellitus (T2DM), and hypercholesterolemia among 57,904 parous women in the Nurses' Health Study II. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between preterm delivery in first pregnancy and each CVD risk factor; adjusted cumulative incidence curves were computed using the Breslow estimator. Results: Preterm delivery (<37 weeks) was associated with HRs of 1.11 (95% CI: 1.06-1.17) for chronic hypertension, 1.17 (95% CI: 1.03-1.33) for T2DM, and 1.07 (95% CI: 1.03-1.11) for hypercholesterolemia, adjusting for age, race/ethnicity, parental education, and prepregnancy confounders (e.g., body mass index, smoking, and family history). HRs were higher in women who delivered very preterm (<32 weeks) and in the first 10 years after first birth. The cumulative incidence of each risk factor was highest in women who delivered very preterm. Conclusions: Women with a history of preterm delivery are at higher risk of developing chronic hypertension, T2DM, and hypercholesterolemia in the years after pregnancy. This increased risk was particularly pronounced in the first 10 years after a preterm delivery, indicating that it may be an important time period to implement lifestyle interventions.

Blood Pressure Response to Exercise and Cardiovascular Disease.

This review aimed to provide a clinical update on exercise blood pressure (BP) and its relationship to cardiovascular disease (CVD), outlining key determinants of abnormal exercise BP responses. We also highlight current evidence gaps that need addressing in order to optimise the relevance of exercise BP as clinical CVD risk factor. Abnormal exercise BP manifests as either exercise hypotension (low BP response) or as exaggerated exercise BP (high BP response). Exercise hypotension is an established sign of existing and likely severe CVD, but exaggerated exercise BP also carries elevated CVD risk due to its association with sub-clinical hypertension. Although exaggerated exercise BP is related to heightened CVD risk at any exercise intensity, recent data suggest that the BP response to submaximal intensity exercise holds greater prognostic and clinical significance than BP achieved at peak/maximal intensity exercise. Cardiorespiratory fitness is a strong modifier of the exercise BP response, and should be taken into consideration when assessing the association with CVD. Both exercise hypotension and exaggerated exercise BP serve as markers that should prompt evaluation for potential underlying CVD. However, the clinical utility of these markers is currently inhibited by the lack of consensus informing the definitions and thresholds for abnormalities in exercise BP.