Associations of Longitudinal Fetal Growth Patterns With Cardiometabolic Factors at Birth

BackgroundBirth weight is associated with cardiometabolic factors at birth. However, it is unclear when these associations occur in fetal life. We aimed to investigate the associations between fetal growth in different gestational periods and cord blood cardiometabolic factors.MethodsWe included 1,458 newborns from the Born in Guangzhou Cohort Study, China. Z-scores of fetal size parameters [weight, abdominal circumference (AC), and femur length (FL)] at 22 weeks and growth at 22–27, 28–36, and ≥37 weeks were calculated from multilevel linear spline models. Multiple linear regression was used to examine the associations between fetal growth variables and z-scores of cord blood cardiometabolic factors.ResultsFetal weight at each period was positively associated with insulin levels, with stronger association at 28–36 weeks (β, 0.31; 95% CI, 0.23 to 0.39) and ≥37 weeks (β, 0.15; 95% CI, 0.10 to 0.20) compared with earlier gestational periods. Fetal weight at 28–36 (β, −0.32; 95% CI, −0.39 to −0.24) and ≥37 weeks (β, −0.26; 95% CI, −0.31 to −0.21) was negatively associated with triglyceride levels, whereas weight at 28–36 weeks was positively associated with HDL levels (β, 0.12; 95% CI, 0.04 to 0.20). Similar results were observed for AC. Fetal FL at 22 and 22–27 weeks was associated with increased levels of insulin, glucose, and HDL.ConclusionsFetal growth at different gestational periods was associated with cardiometabolic factors at birth, suggesting that an interplay between fetal growth and cardiometabolic factors might exist early in pregnancy.

Roles of Cardiometabolic Factors in Mediating the Causal Effect of Type 2 Diabetes on Cardiovascular Diseases: A Two-Step, Two-Sample Multivariable Mendelian Randomization Study

ObjectivesTo investigate the roles of cardiometabolic factors (including blood pressure, blood lipids, thyroid function, body mass, and insulin sensitivity) in mediating the causal effect of type 2 diabetes (T2DM) on cardiovascular disease (CVD) outcomes. DesignTwo-step, two-sample multivariable Mendelian randomization (MVMR) study.SettingInternational genome-wide association study (GWAS) consortia data.ExposureT2DM, blood pressure: systolic blood pressure (SBP), diastolic blood pressure (DBP); blood lipids: low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides (TG); thyroid function: hyperthyroidism, hypothyroidism; body mass index (BMI), waist-hip-ratio (WHR), and insulin sensitivity. Main outcomesCVD including coronary heart disease (CHD), myocardial infarction (MI) and stroke.MethodsSummary-level data for exposures and main outcomes were extracted from GWAS consortia. We used two-sample MR to illustrate the causal effect of T2DM on CVD subtypes and regression-based MVMR to quantify the possible mediation effects of cardiometabolic factors on CVD.ResultsEach additional unit of log odds of T2DM increased 16% risk of CHD [OR: 1.16, 95% confidence interval (CI): 1.12-1.21], 15% risk of MI (OR: 1.15, 95%CI: 1.10-1.20), and 10% risk of stroke (OR: 1.10, 95%CI: 1.06-1.13). In mediation analysis, SBP, DBP and TG were found as main mediators, while the mediation effects of other cardiometabolic factors were not significant. The proportion of total effect of T2DM on CHD mediated by SBP, DBP and TG was 16% (95%CI: 8%-24%), 7% (95%CI: 1%-13%) and 10% (95%CI: 2%-18%), respectively. Mediation effect of SBP and DBP on MI and stroke, TG on MI was also prominent, while mediation effect of TG on stroke was not significant. Combined mediation effect of all three mediators accounted for 29%, 26% and 13% of total effect of T2DM on CHD, MI and stroke, respectively.ConclusionSBP, DBP and TG mediate a substantial proportion of the causal effect of T2DM on CVD and thus interventions on these factors might reduce considerable excess risk of CVD among T2DM patients.

Metabolic Factors Mediate the Association Between Serum Uric Acid to Serum Creatinine Ratio and Cardiovascular Disease

Background The serum uric acid/serum creatinine ratio (SUA/SCr), which represents renal function‐normalized SUA, is associated with diverse adverse outcomes. The aim of this study was to investigate the association between SUA/SCr and cardiovascular disease (CVD), and determine whether and to what extent this association is mediated by cardiometabolic factors. Methods and Results This prospective study enrolled 96 378 participants from the Kailuan study without stroke and myocardial infarction at baseline (2006). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses were conducted to separately explore the mediating effects of cardiometabolic factors on the association between SUA/SCr and CVD. During median follow up of 11.01 years, 6315 (6.55%) individuals developed incident CVD. After adjustment for potential confounders, the highest quartile of SUA/SCr was associated with the highest risk of CVD (HR, 1.15; 95% CI, 1.07–1.23), stroke (HR, 1.16; 95% CI, 1.07–1.26), ischemic stroke (HR, 1.12; 95% CI, 1.02–1.22), and hemorrhagic stroke (HR, 1.36; 95% CI, 1.11–1.65), but not with myocardial infarction (HR, 1.07; 95% CI, 0.92–1.25). The association was consistent across different degrees of kidney function and glucose tolerance statuses. Additionally, the association between high SUA/SCr and CVD was partially mediated by triglycerides (30.74%), body mass index (BMI) (19.52%), total cholesterol (15.06%), hs‐CRP (high‐sensitivity C‐reactive protein) (13.06%), diastolic blood pressure (11.75%), and blood glucose (−16.38%). Conclusions SUA/SCr and CVD were positively associated. Furthermore, this association was partially mediated through blood lipids, BMI, blood pressure, hs‐CRP, and blood glucose.

Association between short-term pulse pressure variability and cardiovascular death among normotensive adults

Background Short-term systolic and diastolic blood pressure variability have been associated with adverse cardiovascular (CVD) outcomes, especially in conjunction with traditional CVD risk factors. However, there are limited data on the relationship between short-term pulse pressure (systolic minus diastolic blood pressure) variability (PPV) and mortality. Purpose We examined the association between PPV and death due to cardiovascular causes. Methods Data from the United States National Health and Nutrition Examination Surveys (NHANES-III, 1988–1994) were linked to death certificates from the National Death Index until December 31, 2015. A total of 6,340 adults (2,981 men and 3,359 non-pregnant women) aged ≥20 years who were normotensive (BP<140/90, without history of hypertension and not taking antihypertensive medication) were followed for an average of 22.3 years. Individuals with any self-reported history of CVD (heart failure, myocardial infarction, stroke) were excluded. PPV was calculated as the standard deviation of six pulse pressure measurements across two visits less than two weeks apart. PPV was categorized into quartiles: Q1: ≤4, Q2: 4.1–6, Q3: 6.1–8, Q4: >8 mmHg. The primary outcome was CVD mortality. Cox proportional hazards models were used to determine hazard ratios, adjusting for demographics & sociobehavioral factors (age, race, ethnicity, poverty-income ratio, smoking status), cardiometabolic factors (waist circumference, HDL, triglycerides, microalbuminuria, diabetes status), BP-related factors (mean pulse pressure, between-visit variability), and accounting for the complex survey design. Results Whereas the proportion of CVD death among men was similar across quartiles, women in Q4 had significantly higher proportion of CVD death (Figure 1; p=0.0055). Women in Q4 of PPV had significantly higher risk of CVD mortality (unadjusted HR 3.63, 95% CI 1.66, 7.90) compared to Q1, even after 1) adjustment for demographics & sociobehavioral factors (HR 2.80, CI 1.40, 5.60), 2) additional adjustment for cardiometabolic factors (HR 2.59, CI 1.33, 5.05), and 3) additional adjustment for mean pulse pressure and between visit variability (HR 2.71, CI 1.42, 5.17). Men in Q4 also had increased, but insignificant, risk of CVD mortality (adjusted HR 1.06, CI 0.38, 2.96). Gender significantly modified the effect of PPV on CVD mortality (p=0.036 for interaction term). When looking at the first visit alone, every 1 mmHg increase in PPV was associated with a 11% significant increase in risk of cardiovascular mortality in females (1.11 [1.03, 1.19]), but only a 1% insignificant increase in males (1.01 [0.91, 1.12]). Conclusions These NHANES data with an average 22.3 years of follow-up indicate that two visit pulse pressure variability is associated with cardiovascular death and that this effect is more pronounced in women. FUNDunding Acknowledgement Type of funding sources: None. Figure 1. Pulse Pressure Variability and Mortality

Psoriatic Arthritis and Metabolic Syndrome: Is There a Role for Disease Modifying Anti-Rheumatic Drugs?

Although psoriatic arthritis (PsA) primarily leads to joint and skin damage, it is associated with higher prevalence of metabolic syndrome (MetS) and its components, namely hypertension, dyslipidemia, obesity, and type II diabetes. Additionally, chronic inflammation is known to aggravate these cardiometabolic factors, thus explaining the enhanced cardiovascular (CV) morbidity and mortality in RA. Furthermore, emerging evidence suggest that some risk factors can fuel inflammation, thus pointing to a bidirectional crosstalk between inflammation and cardiometabolic factors. Therefore, dampening inflammation by disease-modifying anti-rheumatic drugs (DMARDs) may be thought to ameliorate MetS burden and thus, CV risk and disease severity. In fact, recommendations for PsA management emphasize the need of considering comorbidities to guide the treatment decision process. However, the existing evidence on the impact of approved DMARDs in PsA on MetS and MetS components is far from being optimal, thus representing a major challenge for the clinical setting. Although a beneficial effect of some DMARDs such as methotrexate, TNF inhibitors and some small molecules is clear, no head-to-head studies are published and no evidence is available for other therapeutic approaches such as IL-23 or IL-17 inhibitors. This narrative review summarizes the main evidence related to the effect of DMARDs on MetS outcomes in PsA patients and identify the main limitations, research needs and future perspectives in this scenario.

T-Cell Immune Dysregulation and Mortality in Women With Human Immunodeficiency Virus

Summary In women with HIV, higher activation and exhaustion of CD4+ T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression. Background Dysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women. Methods Among 606 women with HIV in the Women’s Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+ and CD8+ T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28–), exhaustion (%PD-1+), and nonactivation/normal function (%CD57–CD28+) with natural-cause, HIV-related, and non-HIV-related mortality. Results At baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+ T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+ T-cell count did not attenuate these associations. CD8+ T-cell markers were not associated with any outcomes adjusting for baseline factors. Conclusions Persistent CD4+ T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression.

Association between Triglyceride Glucose Index and the Risk of Peripheral Artery Disease

Background The triglyceride glucose (TyG) index has been used as a simple surrogate marker of insulin resistance, an independent predictor of atherosclerotic vascular diseases. However, few studies have investigated the relationship between the TyG index and peripheral artery disease (PAD).Methods A total of 3375 participants with comleted TyG and ankle brachial pressure index (ABPI) records were enrolled from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. The TyG index was calculated as ln[triglycerides (mg/dL)×glucose (mg/dL)/2], and the presence of PAD was defined as ABPI ≤ 0.9. Results The participants were 60.1±12.8 year old and 51.3% (1730) were male. The prevelance of PAD was 7.1% (238). Compared with the reference lowest quartile of TyG index, the highest quartile was associated with 1.66-fold (odds ratio [OR], 95% confidence interval [CI] 1.15-2.43; p=0.008) risk of PAD. After adjusted for sociodemographic, lifestyles, and cardiometabolic factors, the multivariate-adjusted OR and 95% CI were 1.55 (1.03-2.37; p=0.039) or participants within the highest quartile. TyG index was also independently and linearly associated with higher presence of PAD (OR 1.27 [1.02-1.56]; p=0.027). Subgroup analysis showed that the association between TyG index and the risk of PAD was still consistant across groups except for obesity.Conclusions Higher TyG index was significantly associated with the higher risk of PAD, which could be a marker of PAD.

Association Between Cardiometabolic Factors and Dizziness in African Americans: The Jackson Heart Study

Background Balance dysfunction is a complex, disabling health condition that can present with multiple phenotypes and etiologies. Data regarding prevalence, characterization of dizziness, or associated factors is limited, especially in an African American population. Purpose The aim of the study is to characterize balance dysfunction presentation and prevalence in an African American cohort, and balance dysfunction relationship to cardiometabolic factors. Research Design The study design is descriptive, cross sectional analysis. Study Sample The study sample consist of N = 1,314, participants in the Jackson Heart Study (JHS). Data Collection and Analysis JHS participants were presented an initial Hearing health screening questionnaire (N = 1,314). Of these, 317 participants reported dizziness and completed a follow-up Dizziness History Questionnaire. Descriptive analysis was used to compare differences in the cohorts' social-demographic characteristics and cardiometabolic variables to the 997 participants who did not report dizziness on the initial screening questionnaire. Based on questionnaire responses, participants were grouped into dizziness profiles (orthostatic, migraine, and vestibular) to further examine differences in cardiometabolic markers as related to different profiles of dizziness. Logistical regression models were adjusted for age, sex, education, reported noise exposure, and hearing sensitivity. Results Participants that reported any dizziness were slightly older and predominantly women. Other significant complaints in the dizzy versus nondizzy cohort included hearing loss, tinnitus, and a history of noise exposure (p < 0.001). Participants that reported any dizziness had significantly higher prevalence of hypertension, blood pressure medication use, and higher body mass index (BMI). Individuals with symptoms alluding to an orthostatic or migraine etiology had significant differences in prevalence of hypertension, blood pressure medication use, and BMI (p < 0.001). Alternatively, cardiometabolic variables were not significantly related to the report of dizziness symptoms consistent with vestibular profiles. Conclusion Dizziness among African Americans is comparable to the general population with regards to age and sex distribution, accordingly to previously published estimates. Participants with dizziness symptoms appear to have significant differences in BMI and blood pressure regulation, especially with associated orthostatic or migraine type profiles; this relationship does not appear to be conserved in participants who present with vestibular etiology symptoms.