Endothelial Dysfunction Is Related to Monocyte Activation in Antiretroviral-Treated People With HIV and HIV-Negative Adults in Kenya

Abstract Background Residual monocyte activation may contribute to increased risk for endothelial dysfunction and subsequent atherosclerotic cardiovascular diseases (CVDs) among people with HIV (PWH) on antiretroviral therapy (ART). We examined the relationship between monocyte activation and endothelial activation in PWH in Kenya. Methods Serum levels of markers of endothelial activation (soluble/circulating intercellular [sICAM-1] and vascular [sVCAM-1] cell adhesion molecule–1), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and monocyte activation (soluble CD14 [sCD14]) were measured in 275 PWH on ART and 266 HIV-negative persons. Linear regression was used to evaluate associations, adjusting for demographic and traditional CVD risk factors. Results Among 541 participants, the median age was 43 years, 50% were female, and most PWH were virally suppressed (97%). sICAM-1 and sVCAM-1 levels were significantly higher in PWH than in HIV-negative participants (P < .001 for both). After further adjustment for traditional CVD risk factors, HIV infection remained associated with 49% (95% CI, 33% to 67%) greater sICAM-1 and 30% (95% CI, 14% to 48%) greater sVCAM-1 relative to uninfected controls. Adjustment for sCD14 substantially attenuated the difference between PWH and HIV-negative individuals. In a stratified analysis of PWH, both sICAM-1 and sVCAM-1 were positively associated with sCD14 (P < .001). Conclusions Despite viral suppression, African PWH have evidence of enhanced endothelial activation associated with sCD14, suggesting that monocyte activation plays a role in atherosclerotic plaque development. Future studies are needed to determine mechanistic pathways leading to monocyte activation in this population.

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Incidence of cardiometabolic diseases in people living with and without HIV in the UK: a population-based matched cohort study

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab420 ◽

2021 ◽

Author(s):

Tiffany E Gooden ◽

Mike Gardner ◽

Jingya Wang ◽

Kate Jolly ◽

Deirdre A Lane ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Heart Disease ◽

Ischaemic Heart Disease ◽

Population Based ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Increased Risk ◽

All Cause Mortality ◽

Hiv Negative

Abstract Background Evidence on the risk of cardiovascular disease (CVD) and CVD risk factors in people with HIV (PWH) is limited. We aimed to identify the risk of composite CVD, individual CVD events and common risk factors. Methods This was a nationwide population-based cohort study comparing adult (≥18y) PWH with HIV-negative individuals matched on age, sex, ethnicity and location. The primary outcome was composite CVD comprising stroke, myocardial infarction (MI), peripheral vascular disease (PVD), ischaemic heart disease and heart failure. The secondary outcomes were individual CVD events, hypertension, diabetes, chronic kidney disease (CKD) and all-cause mortality. Cox proportional hazard regression models were used to examine the risk of each outcome. Results We identified 9233 PWH and 35721 HIV-negative individuals. An increased risk was found for composite CVD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.28-1.77), stroke (aHR 1.42, 95% CI 1.08-1.86), ischaemic heart disease (aHR 1.55, 95% CI 1.24-1.94), hypertension (aHR 1.37, 95% CI 1.23-1.53), type 2 diabetes (aHR 1.28, 95% CI 1.09-1.50), CKD (aHR 2.42, 95% CI 1.98-2.94) and all-cause mortality (aHR 2.84, 95% CI (2.48-3.25). Conclusions PWH have a heightened risk for CVD and common CVD risk factors, reinforcing the importance for regular screening for such conditions.

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Relationship of urinary liver-type fatty acid-binding protein with cardiovascular risk factors in the Japanese population without chronic kidney disease: Sasayama study

BMC Nephrology ◽

10.1186/s12882-021-02398-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yoshimi Kubota ◽

Aya Higashiyama ◽

Mikio Marumo ◽

Masami Konishi ◽

Yoshiko Yamashita ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Proximal Tubular ◽

The Relationship

Abstract Background Urinary liver-type fatty acid-binding protein (L-FABP) is a well-known marker of proximal tubular impairment. We evaluated the relationship between cardiovascular disease (CVD) risk factors and levels of L-FABP in a cross-sectional community-based study. Participants with normoalbuminuria and normal estimated glomerular filtration rate (eGFR), that is, non-chronic kidney disease (non-CKD), were enrolled in this study. To the best of our knowledge, this is the first study to focus on the association between CVD risk factors and a proximal tubular marker in the Japanese general population with normoalbuminuria and normal eGFR. Methods The present study is part of the Sasayama study. The participants included 1000 community residents (447 men and 553 women) aged 40–64 years without a history of CVD or renal dysfunction. Out of these participants 375 men and 477 women, defined as non-CKD, were included for further analysis. In each sex, the highest quintile group was considered to have high-normal L-FABP levels. A multiple logistic regression model was used to evaluate the relationship between risk factors for CVD and high-normal L-FABP levels in the non-CKD participants. We performed a similar analysis using the high-normal urinary albumin to creatinine ratio (UACR) as a dependent variable instead of L-FABP. Results Among the non-CKD participants, in the highest quintile group (Q5, top 20%), L-FABP was ≥2.17 μg/gCre in men and ≥ 2.83 μg/gCre in women. In women, the multivariate odds ratio was 3.62 (1.45–9.00) for high-normal L-FABP in the presence of diabetes mellitus (DM) compared with that in the group without DM. However, the relationship between DM and the UACR level was not significant. In men, DM was significantly associated with high-normal UACR. However, the relationship with L-FABP levels was not significant. Conclusions The presence of DM was more strongly related to high-normal L-FABP levels than to high-normal UACR in women even at the stage of normoalbuminuria and normal eGFR. Our results were also consistent with the findings of a previous study where women were more prone to nonalbuminuric renal impairment compared to men, although further studies are required to confirm the results.

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Patterns of Immune Activation in HIV and Non HIV Subjects and Its Relation to Cardiovascular Disease Risk

Frontiers in Immunology ◽

10.3389/fimmu.2021.647805 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alinda G. Vos ◽

Caitlin N. Dodd ◽

Eveline M. Delemarre ◽

Stefan Nierkens ◽

Celicia Serenata ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Immune Activation ◽

Hiv Positive ◽

Inflammation Markers ◽

Cvd Risk Factors ◽

Immune Markers ◽

Cvd Risk ◽

The Impact ◽

Hiv Negative

IntroductionInsight into inflammation patterns is needed to understand the pathophysiology of HIV and related cardiovascular disease (CVD). We assessed patterns of inflammation related to HIV infection and CVD risk assessed with carotid intima media thickness (CIMT).MethodsA cross-sectional study was performed in Johannesburg, South Africa, including participants with HIV who were virally suppressed on anti-retroviral therapy (ART) as well as HIV-negative participants who were family members or friends to the HIV-positive participants. Information was collected on CVD risk factors and CIMT. Inflammation was measured with the Olink panel ‘inflammation’, allowing to simultaneously assess 92 inflammation markers. Differences in inflammation patterns between HIV-positive and HIV-negative participants were explored using a principal component analysis (PCA) and ANCOVA. The impact of differentiating immune markers, as identified by ANCOVA, on CIMT was assessed using linear regression while adjusting for classic CVD risk factors.ResultsIn total, 185 HIV-positive and 104 HIV negative participants, 63% females, median age 40.7 years (IQR 35.4 – 47.7) were included. HIV-positive individuals were older (+6 years, p <0.01) and had a higher CIMT (p <0.01). No clear patterns of inflammation were identified by use of PCA. Following ANCOVA, nine immune markers differed significantly between HIV-positive and HIV-negative participants, including PDL1. PDL1 was independently associated with CIMT, but upon stratification this effect remained for HIV-negative individuals only.ConclusionHIV positive patients on stable ART and HIV negative controls had similar immune activation patterns. CVD risk in HIV-positive participants was mediated by inflammation markers included in this study.

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The Use of Sex-Specific Factors in the Assessment of Women’s Cardiovascular Risk

Circulation ◽

10.1161/circulationaha.119.043429 ◽

2020 ◽

Vol 141 (7) ◽

pp. 592-599 ◽

Cited By ~ 9

Author(s):

Anandita Agarwala ◽

Erin D. Michos ◽

Zainab Samad ◽

Christie M. Ballantyne ◽

Salim S. Virani

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Primary Prevention ◽

American Heart Association ◽

American Heart ◽

Heart Association ◽

The United States ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Increased Risk

Cardiovascular disease (CVD) is the leading cause of death among women in the United States. As compared with men, women are less likely to be diagnosed appropriately, receive preventive care, or be treated aggressively for CVD. Sex differences between men and women have allowed for the identification of CVD risk factors and risk markers that are unique to women. The 2018 American Heart Association/American College of Cardiology Multi-Society cholesterol guideline and 2019 American College of Cardiology/American Heart Association guideline on the primary prevention of CVD introduced the concept of risk-enhancing factors that are specific to women and are associated with an increased risk of incident atherosclerotic CVD in women. These factors, if present, would favor more intensified lifestyle interventions and consideration of initiation or intensification of statin therapy for primary prevention to mitigate the increased risk. In this primer, we highlight sex-specific CVD risk factors in women, stress the importance of eliciting a thorough obstetrical and gynecological history during cardiovascular risk assessment, and provide a framework for how to initiate appropriate preventive measures when sex-specific risk factors are present.

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Progression of retinopathy and incidence of cardiovascular disease: findings from the Chronic Renal Insufficiency Cohort Study

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2019-315333 ◽

2020 ◽

pp. bjophthalmol-2019-315333

Author(s):

Juan E Grunwald ◽

Maxwell Pistilli ◽

Gui-Shuang Ying ◽

Maureen G Maguire ◽

Ebenezer Daniel ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Cohort Study ◽

Renal Insufficiency ◽

Chronic Renal Insufficiency ◽

Kidney Diseases ◽

Vascular Pathology ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Increased Risk

PurposeChronic kidney disease (CKD) patients often develop cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between progression of retinopathy and concurrent incidence of CVD events in participants with CKD.DesignWe assessed 1051 out of 1936 participants in the Chronic Renal Insufficiency Cohort Study that were invited to have fundus photographs obtained at two timepoints separated by 3.5 years, on average.MethodsUsing standard protocols, presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter calibre were assessed at a retinal image reading centre by trained graders masked to study participants’ information. Participants with a self-reported history of CVD were excluded. Incident CVD events were physician adjudicated using medical records and standardised criteria. Kidney function and proteinuria measurements along with CVD risk factors were obtained at study visits.ResultsWorsening of retinopathy by two or more steps in the EDTRS retinopathy grading scale was observed in 9.8% of participants, and was associated with increased risk of incidence of any CVD in analysis adjusting for other CVD and CKD risk factors (OR 2.56, 95% CI 1.25 to 5.22, p<0.01). After imputation of missing data, these values were OR=1.66 (0.87 to 3.16), p=0.12.ConclusionProgression of retinopathy is associated with higher incidence of CVD events, and retinal-vascular pathology may be indicative of macrovascular disease even after adjustment for kidney diseases and CVD risk factors. Assessment of retinal morphology may provide important information when assessing CVD in patients with CKD.

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Western dietary pattern increases risk of cardiovascular disease in Iranian adults: a prospective population-based study

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2016-0508 ◽

2017 ◽

Vol 42 (3) ◽

pp. 326-332 ◽

Cited By ~ 9

Author(s):

Parvin Mirmiran ◽

Zahra Bahadoran ◽

Azita Zadeh Vakili ◽

Fereidoun Azizi

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Dietary Patterns ◽

Dietary Pattern ◽

Regression Models ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Western Dietary Pattern ◽

Increased Risk

Limited data are available regarding the association of major dietary patterns and risk of cardiovascular disease (CVD) in Middle Eastern countries. We aimed to evaluate the association of major dietary patterns, using factor analysis, with the risk of CVD. Participants without CVD (n = 2284) were recruited from the Tehran Lipid and Glucose Study and were followed for a mean of 4.7 years. Dietary intake of participants was assessed at baseline (2006–2008); biochemical variables were evaluated at baseline and follow-up examination. Multivariate Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate risk of CVD across tertiles of dietary pattern scores. Linear regression models were used to indicate association of dietary pattern scores with changes of CVD risk factors over the study period. Two major dietary patterns, Western and traditional, were identified. During a mean 4.7 ± 1.4 years of follow-up, 57 participants experienced CVD-related events. In the fully adjusted model, we observed an increased risk of CVD-related events in the highest compared to the lowest tertile category of Western dietary pattern score (HR = 2.07, 95% CI = 1.03–4.18, P for trend = 0.01). Traditional dietary pattern was not associated with incidence of CVD or CVD risk factors. A significant association was observed between the Western dietary pattern and changes in serum insulin (β = 5.88, 95% CI = 0.34–11.4). Our findings confirm that the Western dietary pattern, characterized by higher loads of processed meats, salty snacks, sweets, and soft drinks, is a dietary risk factor for CVD in the Iranian population.

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Combined Effects of MMP-7, MMP-8 and MMP-26 on the Risk of Ischemic Stroke

Journal of Clinical Medicine ◽

10.3390/jcm8112011 ◽

2019 ◽

Vol 8 (11) ◽

pp. 2011

Author(s):

Fang-I Hsieh ◽

Hung-Yi Chiou ◽

Chaur-Jong Hu ◽

Jiann-Shing Jeng ◽

Huey-Juan Lin ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Genetic Risk ◽

Genetic Risk Score ◽

Weighted Average ◽

Combined Effects ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Increased Risk ◽

Weighted Genetic Risk Score

Ischemic stroke (IS) is multifactorial causation combining with traditional cardiovascular disease (CVD) and genetic risk factors. Combined effects of MMP-7, MMP-8 and MMP-26 on the risk of IS remain incompletely understood. We aimed to assess individual and joint effects for IS risk by weighted genetic risk score (wGRS) from these three genes and traditional CVD risk factors. A case-control study including 500 cases with IS and 500 stroke-free healthy controls frequency-matched with cases by age and sex was conducted. The wGRS was a weighted average of the number of risk genotype across selected SNPs from MMP-7, MMP-8 and MMP-26. Multivariate logistic regression models were used to analyze the relationship between wGRS and risk of IS. A wGRS in the second tertile was associated with a 1.5-fold increased risk of IS compared with the lowest tertile after adjusting for traditional CVD risk factors. Compared to subjects with low genetic and low modifiable CVD risk, those with high genetic and high modifiable CVD risk had the highest risk of IS (adjusted-OR = 5.75). In conclusion, higher wGRS was significantly associated with an increased risk for IS. A significant interaction between genetic and traditional CVD risk factors was also found on the risk of IS.

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Birthweight in offspring and cardiovascular mortality in their parents, aunts and uncles: a family-based cohort study of 1.35 million births

International Journal of Epidemiology ◽

10.1093/ije/dyz156 ◽

2019 ◽

Vol 49 (1) ◽

pp. 205-215

Author(s):

Fareeha Shaikh ◽

Marte Karoline Kjølllesdal ◽

David Carslake ◽

Camilla Stoltenberg ◽

George Davey Smith ◽

...

Keyword(s):

Risk Factors ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Birth Registry ◽

Nuclear Families ◽

Hazard Ratios ◽

Increased Risk ◽

Paternal Aunt ◽

Family Based ◽

Cvd Mortality

Abstract Background A link between suboptimal fetal growth and higher risk of cardiovascular disease (CVD) is well documented. It has been difficult to assess the contribution of environmental versus genetic factors to the association, as these factors are closely connected in nuclear families. We investigated the association between offspring birthweight and CVD mortality in parents, aunts and uncles, and examined whether these associations are explained by CVD risk factors. Methods We linked Norwegian data from the Medical Birth Registry, the Cause of Death Registry and cardiovascular surveys. A total of 1 353 956 births (1967–2012) were linked to parents and one maternal and one paternal aunt/uncle. Offspring birthweight and CVD mortality association among all relationships was assessed by hazard ratios (HR) from Cox regressions. The influence of CVD risk factors on the associations was examined in a subgroup. Results Offspring birthweight was inversely associated with CVD mortality among parents and aunts/uncles. HR of CVD mortality for one standard deviation (SD) increase in offspring birthweight was 0.72 (0.69–0.75) in mothers and 0.89 (0.86–0.92) in fathers. In aunts/uncles, the HRs were between 0.90 (0.86–0.95) and 0.93 (0.91–0.95). Adjustment for CVD risk factors in a subgroup attenuated all the associations. Conclusions Birthweight was associated with increased risk of CVD in parents and in aunts/uncles. These associations were largely explained by CVD risk factors. Our findings suggest that associations between offspring birthweight and CVD in adult relatives involve both behavioural variables (especially smoking) and shared genetics relating to established CVD risk factors.

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Maternal cardiovascular disease risk factors as predictors of preterm birth in California: a case–control study

BMJ Open ◽

10.1136/bmjopen-2019-034145 ◽

2020 ◽

Vol 10 (6) ◽

pp. e034145

Author(s):

Anne B. Rohlfing ◽

Gregory Nah ◽

Kelli K. Ryckman ◽

Brittney D. Snyder ◽

Deborah Kasarek ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Preterm Birth ◽

Disease Risk ◽

Case Control ◽

Chronic Hypertension ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Increased Risk ◽

Early Preterm Birth

ObjectiveTo determine whether maternal cardiovascular disease (CVD) risk factors predict preterm birth.DesignCase control.SettingCalifornia hospitals.Participants868 mothers with linked demographic information and biospecimens who delivered singleton births from July 2009 to December 2010.MethodsLogistic regression analysis was employed to calculate odds ratios for the associations between maternal CVD risk factors before and during pregnancy (including diabetes, hypertensive disorders and cholesterol levels) and preterm birth outcomes.Primary outcomePreterm delivery status.ResultsAdjusting for the other maternal CVD risk factors of interest, all categories of hypertension led to increased odds of preterm birth, with the strongest magnitude observed in the pre-eclampsia group (adjusted OR (aOR), 13.49; 95% CI 6.01 to 30.27 for preterm birth; aOR, 10.62; 95% CI 4.58 to 24.60 for late preterm birth; aOR, 17.98; 95% CI 7.55 to 42.82 for early preterm birth) and chronic hypertension alone for early preterm birth (aOR, 4.58; 95% CI 1.40 to 15.05). Diabetes (types 1 and 2 and gestational) was also associated with threefold increased risk for preterm birth (aOR, 3.06; 95% CI 1.12 to 8.41). A significant and linear dose response was found between total and low-density lipoprotein (LDL) cholesterol and aORs for late and early preterm birth, with increasing cholesterol values associated with increased risk (likelihood χ2 differences of 8.422 and 8.019 for total cholesterol for late and early, and 9.169 and 10.896 for LDL for late and early, respectively). Receiver operating characteristic curves using these risk factors to predict late and early preterm birth produced C statistics of 0.601 and 0.686.ConclusionTraditional CVD risk factors are significantly associated with an increased risk of preterm birth; these findings reinforce the clinical importance of integrating obstetric and cardiovascular risk assessment across the healthcare continuum in women.

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Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

Current Pharmaceutical Design ◽

10.2174/1381612824666180110102341 ◽

2018 ◽

Vol 24 (3) ◽

pp. 281-290 ◽

Cited By ~ 4

Author(s):

Peter Riis Hansen

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Inflammatory Diseases ◽

Atherosclerotic Cardiovascular Disease ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Chronic Inflammatory Diseases ◽

Increased Risk ◽

Shared Risk

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD.

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