Increased Risk Of Cardiovascular Disease Research Articles

Use of Censored Data Methods to Estimate Blood Pressure Percentiles in US Adults

Abstract Blood pressure (BP) levels are important modifiable risk factors for incident cardiovascular disease (CVD). However, many adults are on anti-hypertensive medication (MEDS) which lowers their BP but is a marker for increased CVD risk. To capture the association of BP and its treatment with risk, it is important to estimate BP levels in the absence of medication, i.e., Underlying BP. One proposed ad-hoc solution is to add a fixed increment e.g., 10/5 mm Hg to systolic (SBP)/diastolic (DBP) for people on MEDS to approximate their Underlying BP. However, what this increment should be, and whether it applies to all MEDS users is unclear. In this manuscript, we propose a novel time-to-event approach to estimate Underlying BP, treating BPs on MEDS as censored observations. The results indicate that the median Treatment Effect (i.e., Underlying BP – Observed BP) for SBP/DBP is 12.0/7.7 for men and 16.9/6.5 for women and is significantly modified by age, BMI and black race. The Underlying BP for MEDS users is then combined with the observed BP for non-MEDS users to derive age-sex-specific BP percentiles for Underlying BP based on a representative sample of normal weight U.S. adults aged 18-79 using NHANES data from 1999-2018.

Reproductive genetics and health.

For those affected, infertility is linked to impaired overall health and reduced life expectancy. In particular, infertile individuals bear an increased risk for cardiovascular disease (CVD) and different types of cancer, partially due to lifestyle differences and to genetic alterations that cause both infertility and an increased cancer risk. Genetic variants causing an increased CVD risk are more commonly found in infertile individuals, but their link to infertility remains unclear. Offspring of infertile couples, conceived via medically assisted reproduction, are as likely as their parents to exhibit or develop adiposity, hormonal alterations such as insulin resistance, and infertility. The effects on health of subsequent generations are completely unclear.

Anxiety and Depression Associated With Increased Cardiovascular Disease Risk Through Accelerated Development of Risk Factors

BackgroundPrior studies have incompletely assessed whether the development of cardiometabolic risk factors (CVDRF) (hypertension, hyperlipidemia, and diabetes mellitus) mediates the association between anxiety and depression (anxiety/depression) and cardiovascular disease (CVD). ObjectivesThe authors aimed to evaluate the following: 1) the association between anxiety/depression and incident CVDRFs and whether this association mediates the increased CVD risk; and 2) whether neuro-immune mechanisms and age and sex effects may be involved. MethodsUsing a retrospective cohort design, Mass General Brigham Biobank subjects were followed for 10 years. Presence and timing of anxiety/depression, CVDRFs, and CVD were determined using ICD codes. Stress-related neural activity, chronic inflammation, and autonomic function were measured by the assessment of amygdalar-to-cortical activity ratio, high-sensitivity CRP, and heart rate variability. Multivariable regression and mediation analyses were employed. ResultsAmong 71,214 subjects (median age 49.6 years; 55.3% female), 27,048 (38.0%) developed CVDRFs during follow-up. Pre-existing anxiety/depression associated with increased risk of incident CVDRF (OR: 1.71 [95% CI: 1.59-1.83], P < 0.001) and with a shorter time to their development (β = −0.486 [95% CI: −0.62 to −0.35], P < 0.001). The development of CVDRFs mediated the association between anxiety/depression and CVD events (log-odds: 0.044 [95% CI: 0.034-0.055], P < 0.05). Neuro-immune pathways contributed to the development of CVDRFs (P < 0.05 each) and significant age and sex effects were noted: younger women experienced the greatest acceleration in the development of CVDRFs after anxiety/depression. ConclusionsAnxiety/depression accelerate the development of CVDRFs. This association appears to be most notable among younger women and may be mediated by stress-related neuro-immune pathways. Evaluations of tailored preventive measures for individuals with anxiety/depression are needed to reduce CVD risk.

Biological aging mediates the association between periodontitis and cardiovascular disease: results from a national population study and Mendelian randomization analysis

BackgroundThe relationship between periodontitis and cardiovascular disease (CVD) has been extensively studied, but the role of biological aging in this relationship remains poorly understood. This study is dedicated to investigating the effect of periodontitis on the incidence of CVD and to elucidating the potential mediating role of biological aging. Furthermore, this study will seek to elucidate the causal association between periodontitis, CVD, and biological aging.MethodsWe included 3269 participants from the National Health and Nutrition Examination Survey (2009–2014) with diagnostic information on periodontitis and composite CVD events. Biological aging was evaluated by utilizing both the Klemera–Doubal method’s calculated biological age (KDMAge) and phenotypic age (PhenoAge). Logistic regression, restricted cubic spline (RCS) analysis, and subgroup analysis were used for data analysis. Mediation analysis was employed to explore the mediating role of biological aging. Subsequently, Mendelian randomization (MR) analyses were performed using genome-wide association study databases to explore potential causal relationships between periodontitis, CVD, and biological aging.ResultsPeriodontitis was associated with a higher risk of CVD. Participants with periodontitis were found to have increased levels of biological aging, and elevated levels of biological aging were associated with increased CVD risk. Mediation analyses showed a partial mediating effect of biological aging (PhenoAge: 44.6%; KDMAge: 22.9%) between periodontitis and CVD risk. MR analysis showed that periodontitis played a causal role in increasing the risk of small vessel stroke, while myocardial infarction was found to increase the risk of periodontitis. In addition, reverse MR analysis showed that phenotypic aging can increase the risk of periodontitis, and there is a two-way causal relationship between CVD and biological aging.ConclusionsPeriodontitis is associated with an increased CVD risk, partially mediated by biological aging, with a complex causal interrelationship. Targeted interventions for periodontal health may slow the biological aging processes and reduce CVD risk.

A Qualitative Exploration of the Impact, Management, and Existing Psychological Support Available for Adults Living with Skin Conditions.

Skin conditions carry a significant physical, psychological, and social burden. People with skin conditions often engage in health-threatening behaviours that can worsen symptoms and increase cardiovascular disease risk. However, access to dedicated psychological and behaviour-change support is limited. The impact, management, and existing psychological support available to adults living with skin conditions was qualitatively explored to inform the development of a psychologically supportive digital intervention. Qualitative research involving a hybrid inductive- deductive approach was performed. Data collection and analysis were theoretically informed by the Common-Sense Model of Self-Regulation. Eight synchronous online group interviews with 43 English-speaking adults (≥ 18 years) with a range of skin conditions were conducted. Data were analysed using Reflexive Thematic Analysis. Three superordinate themes are outlined: (i) visibility underpinning life course impairment, (ii) seeking control amid uncertainty, and (iii) existing support for people with skin conditions. Skin conditions carry a substantial psychological burden, yet dermatology service provision is sub-optimal and patients often resort to seeking support from unreliable sources. Psychological support can have benefits, but barriers exist. This study reinforces the need for high-quality psychological support, and that patients wanted digital means to support effective self- management.

Changes in Atherosclerotic Cardiovascular Disease Risk Scores in a Predominantly Black Cohort with HIV and Associated Comorbidities: A Preliminary Study.

People with HIV (PWH) have an increased risk of atherosclerotic cardiovascular disease (ASCVD) compared to non-PWH, but the reasons for this increased risk remain elusive. We investigated the change in ASCVD risk scores over 4 years to identify clinical factors associated with change in risk scores or high-risk scores. We conducted a preliminary study using retrospective analysis of PWH, between 40 and 75 years old, seen at the Evelyn Jordan Center with at least two routine HIV visits. We collected clinical and demographic data and calculated the ASCVD risk scores using the Pooled Cohort Equation. Exploratory analyses examined change in risk score categories over time. Final adjusted analysis examined factors associated with change in continuous risk scores over time. Our sample included 187 PWH; 166 were black/African American and 79 were female. We found no significant change in ASCVD risk score over time. The risk score was significantly higher in PWH with hepatitis C (7.34%; 95% CI: 2.59, 12.09; p = 0.003) and trended higher in those with dual hepatitis B/C and hepatitis B compared to those without hepatitis (p = 0.07). We found that ASCVD risk did not change over a 4-year period among predominantly black young PWH, but infection with hepatitis C and dual hepatitis B/C were associated with higher ASCVD risk scores. Our findings illustrate the need for further longitudinal studies evaluating change in cardiovascular disease (CVD) risk and investigating viral hepatitis as an added potential contributor to increased CVD risk in high-risk, vulnerable populations.

Association of Urinary Metals With Cardiovascular Disease Incidence and All-Cause Mortality in the Multi-Ethnic Study of Atherosclerosis (MESA).

Exposure to metals has been associated with cardiovascular disease (CVD) end points and mortality, yet prospective evidence is limited beyond arsenic, cadmium, and lead. In this study, we assessed the prospective association of urinary metals with incident CVD and all-cause mortality in a racially diverse population of US adults from MESA (Multi-Ethnic Study of Atherosclerosis). We included 6599 participants (mean [SD] age, 62.1 [10.2] years; 53% female) with urinary metals available at baseline (2000 to 2001) and followed through December 2019. We used Cox proportional hazards models to estimate the adjusted hazard ratio and 95% CI of CVD and all-cause mortality by baseline urinary levels of cadmium, tungsten, and uranium (nonessential metals), and cobalt, copper, and zinc (essential metals). The joint association of the 6 metals as mixture and the corresponding 10-year survival probability was calculated using Cox Elastic-Net. During follow-up, 1162 participants developed CVD, and 1844 participants died. In models adjusted by behavioral and clinical indicators, the HR (95% CI) for incident CVD and all-cause mortality comparing the highest with the lowest quartile were, respectively: 1.25 (1.03, 1.53) and 1.68 (1.43, 1.96) for cadmium; 1.20 (1.01, 1.42) and 1.16 (1.01, 1.33) for tungsten; 1.32 (1.08, 1.62) and 1.32 (1.12, 1.56) for uranium; 1.24 (1.03, 1.48) and 1.37 (1.19, 1.58) for cobalt; 1.42 (1.18, 1.70) and 1.50 (1.29, 1.74) for copper; and 1.21 (1.01, 1.45) and 1.38 (1.20, 1.59) for zinc. A positive linear dose-response was identified for cadmium and copper with both end points. The adjusted HRs (95% CI) for an interquartile range (IQR) increase in the mixture of these 6 urinary metals and the corresponding 10-year survival probability difference (95% CI) were 1.29 (1.11, 1.56) and -1.1% (-2.0, -0.05) for incident CVD and 1.66 (1.47, 1.91) and -2.0% (-2.6, -1.5) for all-cause mortality. This epidemiological study in US adults indicates that urinary metal levels are associated with increased CVD risk and mortality. These findings can inform the development of novel preventive strategies to improve cardiovascular health.

Ambient Air Pollution and Incident Cardiovascular Disease in People with Type 2 Diabetes Mellitus: A cohort study.

We aimed to assess the effect of air pollution on incident cardiovascular disease (CVD) in people with type 2 diabetes mellitus (T2DM). We tracked 486 T2DM patients from 2012 to 2021. Cox regression models were applied to assess the hazard of exposure to particulate matter, carbon monoxide (CO), ozone, nitrogen dioxide, and sulfur dioxide (SO2) on incident CVD, revealing hazard ratios (HRs). CVD incidents occurred in 73 individuals. Among men, each 1-ppm increase in CO levels raised the risk of CVD (HR: 2.66 (95% CI: 1.30-5.44). For women, a 5-ppb rise in SO2 increased CVD risk (HR: 1.60 (95% CI: 1.11-2.30). No notable impact of particulate pollutants was found. Persistent exposure to gaseous air pollutants, specifically CO and SO2, is linked to the development of CVD in men and women with T2DM.

Interferon-free hepatitis C treatment increases a surrogate of atherosclerotic cardiovascular disease risk in Black veterans living with HIV.

Veterans living with HIV (VLWH) and hepatitis C virus (HCV) co-infection have an exacerbated risk of cardiovascular disease (CVD). It is unknown if HCV cure reduces CVD risk in this population. We evaluated changes in low-density lipoprotein (LDL), as a surrogate of CVD risk, 18 months after HCV cure in VLWH. We found significant increases in LDL in VLWH with advanced fibrosis, potentially increasing CVD risk. Lower LDL thresholds to initiate lipid-lowering therapies in VLWH after HCV cure may be warranted.

Synergy Between NK Cells and Monocytes in Potentiating Cardiovascular Disease Risk in Severe COVID-19.

Evidence suggests that COVID-19 predisposes to cardiovascular diseases (CVDs). While monocytes/macrophages play a central role in the immunopathogenesis of atherosclerosis, less is known about their immunopathogenic mechanisms that lead to CVDs during COVID-19. Natural killer (NK) cells, which play an intermediary role during pathologies like atherosclerosis, are dysregulated during COVID-19. Here, we sought to investigate altered immune cells and their associations with CVD risk during severe COVID-19. We measured plasma biomarkers of CVDs and determined phenotypes of circulating immune subsets using spectral flow cytometry. We compared these between patients with severe COVID-19 (severe, n=31), those who recovered from severe COVID-19 (recovered, n=29), and SARS-CoV-2-uninfected controls (controls, n=17). In vivo observations were supported using in vitro assays to highlight possible mechanistic links between dysregulated immune subsets and biomarkers during and after COVID-19. We performed multidimensional analyses of published single-cell transcriptome data of monocytes and NK cells during severe COVID-19 to substantiate in vivo findings. During severe COVID-19, we observed alterations in cardiometabolic biomarkers including oxidized-low-density lipoprotein, which showed decreased levels in severe and recovered groups. Severe patients exhibited dysregulated monocyte subsets, including increased frequencies of proinflammatory intermediate monocytes (also observed in the recovered) and decreased nonclassical monocytes. All identified NK-cell subsets in the severe COVID-19 group displayed increased expression of activation and tissue-resident markers, such as CD69. We observed significant correlations between altered immune subsets and plasma oxidized-low-density lipoprotein levels. In vitro assays revealed increased uptake of oxidized-low-density lipoprotein into monocyte-derived macrophages in the presence of NK cells activated by plasma of patients with severe COVID-19. Transcriptome analyses confirmed enriched proinflammatory responses and lipid dysregulation associated with epigenetic modifications in monocytes and NK cells during severe COVID-19. Our study provides new insights into the involvement of monocytes and NK cells in the increased CVD risk observed during and after COVID-19.

Anthropometric indicators and cardiovascular diseases risk in pre-diabetic and diabetic adults: NHANES 1999–2018 cross-sectional analysis

BackgroundSince cardiovascular disease (CVD) stands as the primary cause of death in those with diabetes, and given the substantial influence of obesity as a common risk factor for both diabetes and atherosclerotic conditions, this investigation sought to find the relationship between anthropometric indicators and CVD risk within these populations. MethodsOur study examined 36,329 adults, including those with diagnosed diabetes, pre-diabetes, and without diabetes from National Health and Nutrition Examination Survey (NHANES) data spanning 1999 to 2018. Various anthropometric indicators such as body mass index (BMI), waist circumference, weight-adjusted waist index (WWI), waist-to-height ratio (WHtR), weight, and height were assessed. Baseline characteristics were compared among the three groups after weighting. Participants were then grouped based on anthropometric indicators, and logistic regression models were used to analyze the association between these indicators and CVD risk in the total diabetes group (including diabetic and pre-diabetic individuals). Threshold effect analysis was conducted to explore nonlinear relationships, and mediation analyses assessed whether serum parameters influenced these relationships. ResultsThis cross-sectional study involved 36,329 participants, weighted to a count of approximately 160.9 million, including over 45.9 million pre-diabetic individuals and around 16.6 million diabetic individuals. Baseline analysis showed significant associations between all six anthropometric indicators and CVD risk across patients with different diabetes statuses. Weighted restricted cubic spline (RCS) curve analysis highlighted increased CVD risk among the total diabetes group for each anthropometric indicator compared to the non-diabetic group. Anthropometric indicators were then divided into quartiles, and after adjusting for confounders, Model 3 revealed that the highest BMI group had a heightened risk of CVD compared to the lowest BMI group. Similar trends were observed in the WWI and WHtR subgroups. Threshold effect analysis of anthropometric indicators unveiled nonlinear associations between waist circumference, height, WWI and CVD risk. Mediation analysis suggested that lipid parameters, especially HDL, significantly mediated these relationships. ConclusionIn individuals with diabetes and pre-diabetes, BMI, weight, and WHtR displayed a consistent, linear increase correlation with CVD risk. Conversely, the link between waist circumference, height, and WWI and CVD risk showcased a more complex, nonlinear pattern. Moreover, HDL level emerged as notable mediator in the association between anthropometric indicators and the risk of CVD.

Long-term association of remnant cholesterol with all-cause and cardiovascular disease mortality: a nationally representative cohort study.

Despite reducing low-density lipoprotein cholesterol (LDL-C) to the normal range, residual cardiovascular risk remain. Remnant cholesterol (RC) exerts a potential residual risk for cardiovascular disease (CVD) prevention, and the long-term longitudinal association between RC and mortality has yet to be well elucidated. This study examined a nationally representative sample of 13,383 adults aged 20 years or older (mean age 45.7 and 52% women) who participated in the NHANES III (from1988 to1994). Causes of death were ascertained by linkage to death records through December 31, 2019. The relations of RC with all-cause and CVD mortality were tested using weighted Cox proportional hazard models. Through a median follow-up of 26.6 years, 5,044 deaths were reported, comprising 1,741 deaths of CVD [1,409 deaths of ischemic heart disease (IHD) and 332 deaths of stroke] and 1,126 of cancer. Compared to those with RC <14.26 mg/dl (lowest quartile), participants with RC ≥29.80 mg/dl (highest quartile) had multivariable-adjusted HRs of 1.23 (95% CI: 1.07-1.42) for all-cause mortality, 1.22 (95% CI: 0.97-1.53) for CVD mortality, and 1.32 (95% CI: 1.03-1.69) for IHD mortality, and 0.89 (95% CI: 0.55-1.43) for stroke mortality, and 1.17 (95% CI 0.90-1.52) for cancer mortality. We observed that elevated RC levels increased CVD risk and IHD mortality despite LDL-C being in the normal range. Elevated blood RC was associated with an increased long-term risk of all-cause, CVD, and IHD mortality. These associations were independent of socioeconomic factors, lifestyles, and history of diseases, and remained robust across the LDL-C stratum. Measuring RC levels might favor clinical assessment of early CVD risk. Further investigation is needed to elucidate the optimal range of RC levels for cardiovascular disease health in the general population.

A biobehavioral observational study to understand the multilevel determinants of cardiovascular health in Black women: the BLOOM Study protocol

BackgroundThe racial/ethnic and gender disparities in cardiovascular disease (CVD) morbidity and mortality in the United States are evident. Across nearly every metric, non-Hispanic Black women have poorer overall cardiovascular health. Emerging evidence shows a disproportionately high burden of increased CVD risk factors in Black women of childbearing age, which has a far-reaching impact on both maternal and child outcomes, resulting in premature onset of CVD and further widens the racial disparities in CVD. There is growing recognition that the fundamental driver of persistent racial/ethnic disparities in CVD, as well as disparities in behavioral risk factors such as physical activity and sleep, is structural racism. Further, the lived personal experience of racial discrimination not only has a negative impact on health behaviors, but also links to various physiological pathways to CVD risks, such as internalized stress resulting in a pro-inflammatory state. Limited research, however, has examined the interaction between daily experience and health behaviors, which are influenced by upstream social determinants of health, and the downstream effect on biological/physiological indicators of cardiovascular health in non-pregnant Black women of childbearing age.Methods/DesignThe BLOOM Study is an observational study that combines real-time ambulatory assessments over a 10-day monitoring period with in-depth cross-sectional lab-based physiological and biological assessments. We will use a wrist-worn actigraphy device to capture 24-h movement behaviors and electronic ecological momentary assessment to capture perceived discrimination, microaggression, and stress. Blood pressure will be captured continuously through a wristband. Saliva samples will be self-collected to assess cortisol level as a biomarker of psychological stress. Lab assessments include a fasting venous blood sample, and assessment of various indices of peripheral and cerebral vascular function/health. Participants’ address or primary residence will be used to obtain neighborhood-level built environmental and social environmental characteristics. We plan to enroll 80 healthy Black women who are between 18 and 49 years old for this study.DiscussionResults from this study will inform the development of multilevel (i.e., individual, interpersonal, and social-environmental levels) lifestyle interventions tailored to Black women based on their lived experiences with the goal of reducing CVD risk.ClinicalTrials.gov IdentifierNCT06150989.

Cardiovascular Risk Factor Management After Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy (HDP) are associated with significantly increased risk of developing future cardiovascular disease (CVD). Obstetricians play a crucial role in CVD prevention for postpartum women and birthing people with HDP because they are primarily responsible for immediate postpartum management and can assist with care transitions to other health care practitioners for long-term management of CVD risk factors. Standardized calculators can be used to evaluate long-term CVD risk, which can help guide intensity of treatment. Emerging technologies such as remote blood pressure monitoring demonstrate promise for improving outcomes among patients with HDP. After HDP, all patients should be advised of their increased CVD risk. A plan should be made to initiate lifestyle modifications and antihypertensive therapy to achieve optimal blood pressure control with a target of lower than 130/80 mm Hg, assess lipids within 2–3 years of delivery, and evaluate for development of type 2 diabetes. Other CVD risk factors such as nicotine use should similarly be identified and addressed. In this review, we summarize the essential components of managing CVD risk after a pregnancy complicated by HDP, including blood pressure monitoring, risk stratification tools, and evidence-based lifestyle recommendations.

Elevated Ambient Temperature Associated With Increased Cardiovascular Disease–Risk Among Patients on Hemodialysis

IntroductionAmbient temperatures have increased due to climate change in many parts of the world. Due to loss of renal function which impacts regulation of thermoregulatory mechanisms the ability to adapt and resilient to changing conditionals is particularly concerning among individuals with kidney failure. The aim of this study is to assess the effect of heat on mortality and health care utilization among US hemodialysis patients. MethodsWe conducted a retrospective analysis 2011-2016 in contiguous United States during warmer months among eligible dialysis patients identified in the United States Renal Data system. Daily ambient temperature was estimated on a 1 km grid and assigned to ZIP-code. Case-crossover design with conditional Poisson models were used to assess the risk of developing adverse health outcomes associated with temperature exposure. ResultsOverall, exposure to high temperature is associated with elevated risk for both mortality and health care utilization among hemodialysis patients. The risk ratios for all-cause mortality and daily temperature were 1.07 (95% CI: 1.03-1.11), 1.17 (1.14-1.21) for fluid disorder-related hospital admissions, and 1.19 (1.16-1.22) for cardiovascular event-related emergency department visits, comparing 99th percentile vs. 50th percentile daily temperatures. Larger effects were observed for cumulative lagged exposure three-days prior to the outcome and for Southwest and Northwest climate regions. ConclusionHeat exposure is associated with elevated risk for CVD-related mortality and health care utilization among this vulnerable population. Furthermore, the effect appears to be potentially cumulative in the short-term, and varies geographically.

Association of retinal image-based, deep learning cardiac BioAge with telomere length and cardiovascular biomarkers.

Our retinal image-based deep learning (DL) cardiac biological age (BioAge) model could facilitate fast, accurate, noninvasive screening for cardiovascular disease (CVD) in novel community settings and thus improve outcome with those with limited access to health care services. This study aimed to determine whether the results issued by our DL cardiac BioAge model are consistent with the known trends of CVD risk and the biomarker leukocyte telomere length (LTL), in a cohort of individuals from the UK Biobank. A cross-sectional cohort study was conducted using those individuals in the UK Biobank who had LTL data. These individuals were divided by sex, ranked by LTL, and then grouped into deciles. The retinal images were then presented to the DL model, and individual's cardiac BioAge was determined. Individuals within each LTL decile were then ranked by cardiac BioAge, and the mean of the CVD risk biomarkers in the top and bottom quartiles was compared. The relationship between an individual's cardiac BioAge, the CVD biomarkers, and LTL was determined using traditional correlation statistics. The DL cardiac BioAge model was able to accurately stratify individuals by the traditional CVD risk biomarkers, and for both males and females, those issued with a cardiac BioAge in the top quartile of their chronological peer group had a significantly higher mean systolic blood pressure, hemoglobin A 1c , and 10-year Pooled Cohort Equation CVD risk scores compared with those individuals in the bottom quartile (p<0.001). Cardiac BioAge was associated with LTL shortening for both males and females (males: -0.22, r2 = 0.04; females: -0.18, r2 = 0.03). In this cross-sectional cohort study, increasing CVD risk whether assessed by traditional biomarkers, CVD risk scoring, or our DL cardiac BioAge, CVD risk model, was inversely related to LTL. At a population level, our data support the growing body of evidence that suggests LTL shortening is a surrogate marker for increasing CVD risk and that this risk can be captured by our novel DL cardiac BioAge model.

Advanced cardiovascular physiology in an individual with type 1 diabetes after 10-year ketogenic diet.

Adults with type 1 diabetes (T1D) have an elevated risk for cardiovascular disease (CVD) compared with the general population. HbA1c is the primary modifiable risk factor for CVD in T1D. Fewer than 1% of patients achieve euglycemia (<5.7% HbA1c). Ketogenic diets (KD; ≤50 g carbohydrate/day) may improve glycemia and downstream vascular dysfunction in T1D by reducing HbA1c and insulin load. However, there are concerns regarding the long-term CVD risk from a KD. Therefore, we compared data collected in a 60-day window in an adult with T1D on exogenous insulin who consumed a KD for 10 years versus normative values in those with T1D (T1D norms). The participant achieved euglycemia with an HbA1c of 5.5%, mean glucose of 98 [5] mg/dL (median [interquartile range]), 90 [11]% time-in-range 70-180 mg/dL (T1D norms: 1st percentile for all), and low insulin requirements of 0.38 ± 0.03 IU/kg/day (T1D norms: 8th percentile). Seated systolic blood pressure (SBP) was 113 mmHg (T1D norms: 18th percentile), while ambulatory awake SBP was 132 ± 15 mmHg (T1D target: <130 mmHg), blood triglycerides were 69 mg/dL (T1D norms: 34th percentile), low-density lipoprotein was 129 mg/dL (T1D norms: 60th percentile), heart rate was 56 beats/min (T1D norms: >1SD below the mean), carotid-femoral pulse wave velocity was 7.17 m/s (T1D norms: lowest quartile of risk), flow-mediated dilation was 12.8% (T1D norms: >1SD above mean), and cardiac vagal baroreflex gain was 23.5 ms/mmHg (T1D norms: >1SD above mean). Finally, there was no indication of left ventricular diastolic dysfunction from echocardiography. Overall, these data demonstrate below-average CVD risk relative to T1D norms despite concerns regarding the long-term impact of a KD on CVD risk.NEW & NOTEWORTHY Adults with type 1 diabetes (T1D) have a 10-fold higher risk for cardiovascular disease (CVD) compared with the general population. We assessed cardiovascular health metrics in an adult with T1D who presented with a euglycemic HbA1c after following a ketogenic diet for the past 10 years. Despite concerns about the ketogenic diet increasing CVD risk, the participant exhibited below-average CVD risk relative to others with T1D when considering all outcomes together.

Sympathetic and blood pressure reactivity in young adults with major depressive disorder

BackgroundSympathetic and blood pressure (BP) hyper-reactivity to stress may contribute to increased cardiovascular disease (CVD) risk in adults with major depressive disorder (MDD); however, whether this is evident in young adults with MDD without comorbid disease remains unclear. We hypothesized that acute stress-induced increases in muscle sympathetic nerve activity (MSNA) and BP would be exaggerated in young adults with MDD compared to healthy non-depressed young adults (HA) and that, in adults with MDD, greater symptom severity would be positively related to MSNA and BP reactivity. MethodsIn 28 HA (17 female) and 39 young adults with MDD of mild-to-moderate severity (unmedicated; 31 female), MSNA (microneurography) and beat-to-beat BP (finger photoplethysmography) were measured at rest and during the cold pressor test (CPT) and Stroop color word test (SCWT). ResultsThere were no group differences in resting MSNA (p = 0.24). Neither MSNA nor BP reactivity to either the CPT [MSNA: ∆24 ± 10 HA vs. ∆21 ± 11 bursts/min MDD, p = 0.67; mean arterial pressure (MAP): ∆22 ± 7 HA vs. ∆21 ± 10 mmHg MDD, p = 0.46)] or the SCWT (MSNA: ∆-4 ± 6 HA vs. ∆-5 ± 8 bursts/min MDD, p = 0.99; MAP: ∆7 ± 8 HA vs ∆9 ± 5 mmHg MDD; p = 0.82) were different between groups. In adults with MDD, symptom severity predicted MAP reactivity to the CPT (β = 0.78, SE = 0.26, p = 0.006), but not MSNA (p = 0.42). LimitationsThe mild-to-moderate symptom severity reflects only part of the MDD spectrum. ConclusionsNeither sympathetic nor BP stress reactivity are exaggerated in young adults with MDD; however, greater symptom severity may amplify BP reactivity to stress, thereby increasing CVD risk.

While You Are Sleeping: Marital Ambivalence and Blunted Nocturnal Blood Pressure.

Marital relationships offer health benefits, including a lower risk of cardiovascular disease (CVD). However, quality of the relationship matters; ambivalent behaviors may increase CVD risk by affecting blunted nocturnal blood pressure (BP) dipping. This study tracked daytime and nocturnal SBP and DBP in 180 normotensive individuals (90 couples; participant mean age 25.04; 91.58% white) over a 24 h period using ambulatory blood pressure monitors to explore the impact of martial quality. Results showed that perceptions of spousal ambivalence were associated with blunted nocturnal BP dipping. Perceptions of one's own behavior as ambivalent also showed blunted nocturnal dipping. When in an ambivalent relationship, a gender interaction was found such that women were most likely to have blunted SBP dipping, but men were more likely to have blunted nocturnal DBP dipping. Overall, this study found an association between ambivalence and BP dipping, thus uncovering one virtually unexplored pathway by which marital relationships may have adverse effects on health.

Divergent age-associated and metabolism-associated gut microbiome signatures modulate cardiovascular disease risk.

Insight into associations between the gut microbiome with metabolism and aging is crucial for tailoring interventions to promote healthy longevity. In a discovery cohort of 10,207 individuals aged 40-93 years, we used 21 metabolic parameters to classify individuals into five clusters, termed metabolic multimorbidity clusters (MCs), that represent different metabolic subphenotypes. Compared to the cluster classified as metabolically healthy (MC1), clusters classified as 'obesity-related mixed' (MC4) and 'hyperglycemia' (MC5) exhibited an increased 11.1-year cardiovascular disease (CVD) risk by 75% (multivariable-adjusted hazard ratio (HR): 1.75, 95% confidence interval (CI): 1.43-2.14) and by 117% (2.17, 1.72-2.74), respectively. These associations were replicated in a second cohort of 9,061 individuals with a 10.0-year follow-up. Based on analysis of 4,491 shotgun fecal metagenomes from the discovery cohort, we found that gut microbial composition was associated with both MCs and age. Next, using 55 age-specific microbial species to capture biological age, we developed a gut microbial age (MA) metric, which was validated in four external cohorts comprising 4,425 metagenomic samples. Among individuals aged 60 years or older, the increased CVD risk associated with MC4 or MC5, as compared to MC1, MC2 or MC3, was exacerbated in individuals with high MA but diminished in individuals with low MA, independent of age, sex and other lifestyle and dietary factors. This pattern, in which younger MA appears to counteract the CVD risk attributable to metabolic dysfunction, implies a modulating role of MA in cardiovascular health for metabolically unhealthy older people.