Effect Of Systolic Blood Pressure Research Articles

The association of lipid metabolism with bone metabolism and the role of human traits: a Mendelian randomization study.

The impact of lipid metabolism on bone metabolism remains controversial, and the extent to which human traits mediate the effects of lipid metabolism on bone metabolism remains unclear. This study utilized mendelian randomization to investigate the effects of blood lipids on bone mineral density (BMD) at various skeletal sites and examined the mediating role of human traits in this process. We leveraged genetic data from large-scale genome-wide association studies on blood lipids (n=1,320,016), forearm bone mineral density (FA-BMD) (n=10,805), lumbar spine bone mineral density (LS-BMD) (n=44,731), and femoral neck bone mineral density (FN-BMD) (n=49,988) to infer causal relationships between lipid and bone metabolism. The coefficient product method was employed to calculate the indirect effects of human traits and the proportion of mediating effects. The results showed that a 1 standard deviation(SD) increase in HDL-C, LDL-C and TC was associated with a decrease in LS-BMD of 0.039 g/cm2, 0.045 g/cm2 and 0.054 g/cm2, respectively. The proportion of mediating effects of systolic blood pressure (SBP) on HDL-C to LS-BMD was 3.17%, but suppression effects occurred in the causal relationship of LDL-C and TC to LS-BMD. Additionally, the proportion of mediating effects of hand grip strength (HGS) on the TC to LS-BMD pathway were 6.90% and 4.60% for the left and right hands, respectively. In conclusion, a negative causal relationship was established between lipid metabolism and bone metabolism. Our results indicated that SBP and HGS served as mediators for the effects of lipid metabolism on bone metabolism.

Mendelian randomization study of the relevance of blood pressure to vascular mortality among 150,000 participants in the mexico city prospective study

Abstract Background Mendelian randomization (MR) studies are commonly used to reduce confounding and reverse-causality when estimating the effects of risk factors on disease and provide estimates of effects over the whole life-course. However, most previous MR studies have been conducted in populations of European-ancestry. We used MR to investigate the effect of systolic blood pressure (SBP) on vascular mortality at ages 35-74 in a large prospective study of Mexican adults. Methods Between 1998 and 2004, 150,000 adults aged ≥35 years were recruited into the Mexico City Prospective Study and followed for median 19 years(1,2). Using 886 externally-selected single nucleotide polymorphisms (SNPs)(3) we created a genetic risk score for SBP (GRS-SBP). Those taking an antihypertensive drug at recruitment had their SBP adjusted by +6 mmHg(2) (adjustment by +15 mmHg rather than +6 mmHg was done in a sensitivity analysis). Cox regression and the MR ‘ratio’ method were then used to estimate the causal effect of SBP on vascular mortality at ages 35-74 years. Analyses were adjusted for age at risk, sex, residential district, education, smoking, alcohol consumption, physical activity, adiposity, diabetes mellitus and the first 7 genetic principal components. They excluded those aged ≥75 years, had incomplete data, or had prior vascular disease or any other chronic condition (except diabetes). Alternative MR approaches (inverse-variance-weighted, weighted median and MR Egger) were used for sensitivity analyses. Conventional epidemiological analyses of the association between SBP and mortality after correction for regression dilution bias were also done. Results Among 127,849 included individuals, the GRS-SBP explained 1.9% of baseline SBP variation. Those in the top fifth of the GRS-SBP distribution had 6.6 mmHg higher SBP and twice the prevalence of self-reported hypertension and antihypertensive drug use than those in the bottom fifth, but the GRS-SBP was uncorrelated with other factors. The strength of association between GRS-SBP and measured SBP was broadly similar in men and women, at different ages, and between people with different proportions of Amerindian genetic ancestry. Using the ratio method and a single estimate of the association of GRS-SBP with SBP, each 10 mmHg higher genetically predicted SBP was associated with 58% higher vascular mortality at ages 35-74 years (RR 1.58, 95% CI 1.27-1.96), including 69% higher ischaemic heart disease mortality (RR 1.69, 95% CI 1.31-2.16) and 65% higher stroke mortality (RR 1.65, 1.15-2.33). These genetic estimates were somewhat larger than conventional observational associations of usual SBP to risk. Alternative MR approaches found no evidence of pleiotropy and yielded similar conclusions. Conclusions These MR analyses confirm that blood pressure is a major cause of premature death from vascular diseases in Mexican adults.

Cardiovascular responses to combined mechanoreflex and metaboreflex activation in healthy adults: effects of sex and low- versus high-hormone phases in females.

Females generally have smaller blood pressure (BP) responses to isolated muscle mechanoreflex and metaboreflex activation compared with males, which may explain sex differences in BP responses to voluntary exercise. The mechanoreflex may be sensitized during exercise, but whether mechanoreflex-metaboreflex interactions differ by sex or variations in sex hormones remains unknown. Thirty-one young healthy subjects (females, n = 16) performed unilateral passive cycling (mechanoreflex), active cycling (40% peak Watts), postexercise circulatory occlusion (PECO; metaboreflex), and passive cycling combined with PECO (combined mechanoreflex and metaboreflex activation). Beat-to-beat BP, heart rate, inactive leg vascular conductance, and active leg muscle oxygenation were measured. Ten females underwent exploratory testing during low- and high-hormone phases of their self-reported menstrual cycle or oral contraceptive use. Systolic BP and heart rate responses did not differ between sexes during active cycling [Δ30 ± 9 vs. 29 ± 11 mmHg (males vs. females), P = 0.9; Δ33 ± 8 vs. 35 ± 6 beats/min, P = 0.4] or passive cycling with PECO (Δ26 ± 11 vs. 21 ± 10 mmHg, P = 0.3; Δ14 ± 7 vs. 18 ± 15 beats/min, P = 0.3). Passive cycling with PECO revealed additive, not synergistic, effects for systolic BP [males: Δ23 ± 14 vs. 26 ± 11 mmHg (sum of isolated passive cycling and PECO vs. combined activation); females: Δ26 ± 11 vs. 21 ± 12 mmHg, interaction P = 0.05]. Results were consistent in subset analyses with sex differences in active cycling BP (P > 0.1) and exploratory analyses of hormone phase (P > 0.4). Despite a lack of statistical equivalence, no differences in cardiovascular responses were found during combined mechanoreflex-metaboreflex activation between sexes or hormone levels. These results provide preliminary data regarding the involvement of muscle mechanoreflex-metaboreflex interactions in mediating sex differences in voluntary exercise BP responses.NEW & NOTEWORTHY The muscle mechanoreflex may be sensitized by metabolites during exercise. We show that cardiovascular responses to combined mechanoreflex (passive cycling) and metaboreflex (postexercise circulatory occlusion) activation are primarily additive and do not differ between males and females, or across variations in sex hormones in females. Our findings provide new insight into the contributions of muscle mechanoreflex-metaboreflex interactions as a cause for prior reports that females have smaller blood pressure responses to voluntary exercise.

Impact of the Level of Adherence to the DASH Diet on Blood Pressure: A Systematic Review and Meta-Analysis.

Introduction: the objective of our study was to systematically review the current literature and perform a meta-analysis to evaluate the effect of the level of adherence to the DASH diet on blood pressure. Methods: The identification of relevant studies, data extraction and critical appraisal of the included studies were performed independently by two reviewers. A random-effects model was employed to synthesize the available evidence using the standardized mean difference (SMD) as the appropriate effect size. Results: A total of 37 and 29 articles were included in the qualitative and quantitative analysis, respectively. The pooled effect for systolic blood pressure was SMD = -0.18 (95%CI: -0.32 to -0.04; I2 = 94%; PI: -0.93 to 0.57) and for diastolic blood pressure it was SMD = -0.13 (95%CI: -0.19 to -0.06; I2 = 94%; PI: -0.42 to 0.17). Conclusions: Our findings showed that greater adherence to the DASH diet has a beneficial effect on blood pressure compared to the lowest adherence. Increased compliance with DASH diet recommendations might also have a positive effect on cardiometabolic factors and overall health status. Future studies should aim to standardize the tools of adherence to the DASH diet and utilize rigorous study designs to establish a clearer understanding of the potential benefits of the level of adherence to the DASH diet in blood pressure management.

EXERCISE RELATED HYPOTENSIVE EFFECT IN A CARDIAC REHABILITATION PROGRAM AS A POSSIBLE PROGNOSTIC MARKER OF CARDIOVASCULAR RISK

Objective: There are some studies that analyze the correlation between the magnitude of the hypotensive effect after exercise and the long-term cardiovascular benefit. However, this same effect in a cardiac rehabilitation program (CRP) is unknown. The aim was meausuring the benefit of this effect in patients undergoing a cardiac rehabilitation program. Design and method: We analyzed 19 patients who completed a CRP for 3 months (2 weekly sessions of cardiovascular and resistance exercise), in the period between September 2021 and September 2022, after an Acute Coronary Syndrome or hospitalization for Decompensated Heart Failure. In each rehabilitation session, the blood pressure values were evaluated before the beginning of the exercise and after (1st minute and 5th minute of recovery). The effect was compared in two different moments of the program - 1st and 12th session - having defined as main “outcome” a magnitude of higher systolic blood pressure drop in the 12th compared to the 1st session. After completion of the CRP, all patients included in the study were given two validated questionnaires to assess insomnia (“Insomnia Severity Index – ISI”) and the impact of the current illness on quality of life (EQ-5D). Results: Regarding the patients included, the clinical and sociodemographic characteristics are described in table 1. Comparing males and females, using a T-student analysis, there was a statistically significant difference in relation to a greater systolic hypotensive effect in the male group compared to the female group (91.7% vs 40.0%, p < 0.05) – table 2. Regarding the analysis of the impact on quality of life, the total number of patients with improvement in the hypotensive effect of systolic blood pressure showed statistically significant lower values in the questionnaire (EQ5D) – 6.8±1.3 vs 9.0±1.0 (p<0.05) and higher in the score of insomnia 10.7 ± 9.0 vs. 3.9 ± 4.1 - table 2. Conclusions: The systolic hypotensive effect of exercise, observed in the rehabilitation program of the current study, is associated with better rates of insomnia and impact on quality of life. The authors intend to confirm this hypothesis in the longitudinal evaluation of future events.

Systolic, diastolic blood pressure and pulse pressure and risk of stroke in young aged patients with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background It is well-known that higher blood pressure (BP) is associated with a higher risk of stroke with atrial fibrillation (AF). However, there is limited data about the effect of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) on the risk of ischemic stroke in young and low-risk AF patients Methods Using the Korean Health Insurance Service database, patients who were newly diagnosed with AF between January 2009 and December 2016 and had health screening examination data within 2-year after AF diagnosis were included. Patients aged between 20 and 39 years were finally included in this analysis. During follow-up, incident ischemic stroke was evaluated as a primary outcome. Hazard ratio (HR) and the corresponding 95% confidence intervals (CI) were calculated using multivariable Cox proportional hazard models. Results A total of 15,980 patients were included in this analysis (mean age 32.4±4.8 years, 66.9% of men). Mean CHA2DS2-VASc score was 0.7±0.8 and oral anticoagulation rate was 5.6%. During a median 5.2-year of follow-up, 73 patients had an incident ischemic stroke (incidence rate, 0.9 per 1,000 person-years). After multivariable adjustment, SBP ranging from 140 to 159 mmHg and 160 mmHg or higher were associated with a significantly higher risk of ischemic stroke by 8.4-fold and 11.6-fold compared to SBP under 100 mmHg (Figure). DBP 95mmHg or higher was associated with a higher risk of ischemic stroke by 4.2-fold than DBP under 65 mmHg (Figure). Patients with PP ranging from 50 to 59 mmHg and 60 mmHg or higher showed a significantly higher risk of ischemic stroke than those with PP ranging from 40 to 49 mmHg (HR [95% CI]; 1.81 [1.04-3.18] and 3.15 [1.49-6.64], respectively). Also, lower PP than 30 mmHg was associated with a higher risk of stroke (3.96 [1.36-11.53]). Conclusion Optimal BP control might be crucial to preventing ischemic stroke in these young and low-risk AF patients.

Mediation analysis for high-dimensional mediators and outcomes with an application to multimodal imaging data

Multimodal neuroimaging data have attracted increasing attention for brain research. An integrated analysis of multimodal neuroimaging data and behavioral or clinical measurements provides a promising approach for comprehensively and systematically investigating the underlying neural mechanisms of different phenotypes. However, such an integrated data analysis is intrinsically challenging due to the complex interactive relationships between the multimodal multivariate imaging variables. To address this challenge, a novel multivariate-mediator and multivariate-outcome mediation model (MMO) is proposed to simultaneously extract the latent systematic mediation patterns and estimate the mediation effects based on a dense bi-cluster graph approach. A computationally efficient algorithm is developed for dense bi-cluster structure estimation and inference to identify the mediation patterns with multiple testing correction. The performance of the proposed method is evaluated by an extensive simulation analysis with comparison to the existing methods. The results show that MMO performs better in terms of both the false discovery rate and sensitivity compared to existing models. The MMO is applied to a multimodal imaging dataset from the Human Connectome Project to investigate the effect of systolic blood pressure on whole-brain imaging measures for the regional homogeneity of the blood oxygenation level-dependent signal through the cerebral blood flow.

The long-term reproducibility of the white-coat effect on blood pressure as a continuous variable from the Ohasama Study

There is little information about the reproducibility of the white coat effect, which was treated as a continuous variable. To investigate a long-term interval reproducibility of the white-coat effect as a continuous variable. We selected 153 participants without antihypertensive treatment (men, 22.9%; age, 64.4 years) from the general population of Ohasama, Japan, to assess the repeatedly measured white-coat effect (the difference between blood pressures at the office and home) in a 4-year interval. The reproducibility was assessed by testing the intraclass correlation coefficient (two-way random effect model-single measures). The white-coat effect for systolic/diastolic blood pressure slightly decreased by 0.17/1.56 mmHg at the 4-year visit on average. The Bland–Altman plots showed no significant systemic error for the white-coat effects (P ≥ 0.24). The intraclass correlation coefficient (95% confidence interval) of the white-coat effect for systolic blood pressure, office systolic blood pressure, and home systolic blood pressure were 0.41 (0.27–0.53), 0.64 (0.52–0.74), and 0.74 (0.47–0.86), respectively. Change in the white-coat effect was mainly affected by a change in office blood pressure. Long-term reproducibility of the white-coat effect is limited in the general population without antihypertensive treatment. The change in the white-coat effect is mainly caused by office blood pressure variation.

The Effect of Systolic Blood Pressure on Cement Penetration Depth in Primary Total Knee Arthroplasty

Background: Cement Penetration Depth (CPD) into bone is an important factor for successful Total Knee Arthroplasties (TKA). Our study investigated the effect of Systolic Blood Pressure (SBP) on average tibial, femoral and total CPD in primary TKA. Methods and Findings: In this retrospective cohort study, patients who had a primary TKA between November 2018 and February 2020 at four, academic medical centers were included. CPD was evaluated according to the Knee Society Radiographic Evaluation System on radiographs one month post-operatively. Two independent evaluators measured four zones of tibial penetration and three zones of femoral penetration and averaged their results. The measurements were combined to create an average tibial, average femoral and average total CPD. SBP was collected at the 3/4 time of surgery length- the estimated time of cementation. 1221 primary TKA cases were included in the study – 1128 in the tourniquet group and 93 in the tourniquet-less group. There were no significant differences between the age, sex, BMI, or LOS between the two cohorts. A multiple, multivariate analysis was performed. In the tourniquet-less group, SBP did not significantly affect average tibial CPD (p=0.98), average femoral CPD (p=0.45), or average total CPD (p=0.23). However, tourniquet use was found to significantly increase average femoral (p<0.001) and total penetration (p=0.001). Conclusion: SBP did not significantly affect tibial, femoral, or total CPD in patients undergoing tourniquet-less, primary TKA. However, the use of a tourniquet significantly aids in average femoral and total CPD. The clinical significance of this difference needs further investigation.

129: BLOOD PRESSURE REDUCTION AND RISK OF ACUTE KIDNEY INJURY IN PATIENTS WITH AORTIC SYNDROMES

Introduction: Acute kidney injury (AKI) occurs frequently in patients with aortic dissection and is associated with increased hospitalization and early mortality. It is unclear whether AKI is a consequence of the aortic syndrome itself or attributable to rapid hemodynamic changes that result from strict blood pressure and heart rate goals. The objective of this study was to evaluate the effect of systolic blood pressure (SBP) reduction on risk of AKI in patients with aortic syndromes, with the hypothesis that patients who experience AKI will have a higher magnitude of SBP reduction. Methods: This was a single-center, retrospective cohort study conducted at an academic medical center. Patients were ≥18 years old, hospitalized from January 1, 2015 to December 31, 2021 with an aortic syndrome, and treated with antihypertensive infusions. The primary outcome was the difference between maximum SBP reduction in the no-AKI and AKI group at 4, 8, 12, and 24 hours. Secondary outcomes were accuracy of maximum SBP reduction in predicting AKI and the optimal SBP cutoff that predicts AKI. Student’s t-test was used to compare maximum SBP reduction between cohorts. Receiver operating characteristic (ROC) analysis was used for the secondary outcomes. Area under the curve (AUC) and SBP cutoff point were calculated as part of the ROC analysis. Chi-squared test was used to calculate risk of AKI when exceeding the SBP cutoff. Results: A total of 71 patients were analyzed (n = 48, no-AKI; n = 23, AKI). Seventy-six percent of patients had Type B aortic dissection, and mean SBP at baseline was 176 ±26 mmHg. For the primary outcome, there was a significant difference in maximum SBP reduction at all time points between the no-AKI and AKI group (4 hours, 47 vs 70 mmHg; 8 hours, 56 vs 82 mmHg; 12 hours, 62 vs 87 mmHg; 24 hours, 69 vs 95 mmHg; p < 0.001 for all comparisons). Maximum SBP reduction over 4, 8, 12, and 24 hours yielded an AUC-ROC of 0.77, 0.80, 0.79, and 0.79, respectively. Lowering SBP ≥54 mmHg within the first 4 hours significantly increased risk of AKI (OR, 6.65; 95% confidence interval, 1.88-19.72; p < 0.001). Conclusions: Patients with aortic syndromes who experience AKI have a higher magnitude of SBP reduction than those who do not experience AKI. Maximum SBP reduction appears to be an accurate predictor of AKI.

Using Genomic Structural Equation Modeling to Partition the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors into Maternal and Offspring Components in the Norwegian HUNT Study

The Barker Hypothesis posits that adverse intrauterine environments result in fetal growth restriction and increased risk of cardiometabolic disease through developmental compensations. Here we introduce a new statistical model using the genomic SEM software that is capable of simultaneously partitioning the genetic covariation between birthweight and cardiometabolic traits into maternally mediated and offspring mediated contributions. We model the covariance between birthweight and later life outcomes, such as blood pressure, non-fasting glucose, blood lipids and body mass index in the Norwegian HUNT study, consisting of 15,261 mother-eldest offspring pairs with genetic and phenotypic data. Application of this model showed some evidence for maternally mediated effects of systolic blood pressure on offspring birthweight, and pleiotropy between birthweight and non-fasting glucose mediated through the offspring genome. This underscores the importance of genetic links between birthweight and cardiometabolic phenotypes and offer alternative explanations to environmentally based hypotheses for the phenotypic correlation between these variables.

The correlation between testosterone and stroke and the mediating role of blood pressure: The Henan rural cohort study

AimsWe aimed to investigate the association of serum testosterone with stroke and calculate the proportion explained by blood pressure on this association. Materials and methodsA total of 6175 subjects were included in this study. Serum testosterone was quantified by liquid chromatography‐tandem mass spectrometry. The logistic regression model was used to evaluate the association between serum testosterone and stroke. Linear regression analysis was used to assess the associations of serum testosterone with blood pressure. In addition, mediation analysis was performed to identify the mediation effects of blood pressure on the association of serum testosterone with stroke. Sex-stratified analysis was employed throughout the research. ResultsAfter adjusting for multiple variables, serum testosterone levels were negatively associated with stroke in males (per 1 unit natural log‐transformed, odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.69-0.94; Tertile 3 vs Tertile 1, OR = 0.65, 95% CI:0.44-0.96). Furthermore, blood pressure played a partial mediating role in the relationship between testosterone and stroke in males. The indirect effect/total effect of systolic blood pressure, diastolic blood pressure and mean arterial pressure were 7.37%, 9.54% and 9.22%, respectively. Notably, the relationship between testosterone and stroke and the role of blood pressure in regulating them was not observed in females. ConclusionThis study describes that in rural Chinese males, testosterone can reduce the risk of stroke by affecting blood pressure. To some extent, we provide a new epidemiological evidence for the relationship between testosterone and stroke.

Unravelling the Distinct Effects of Systolic and Diastolic Blood Pressure Using Mendelian Randomisation.

A true discrepancy between the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on cardiovascular (CV) outcomes remains unclear. This study performed two-sample Mendelian randomization (MR) using genetic instruments that exclusively predict SBP, DBP or both to dissect the independent effect of SBP and DBP on a range of CV outcomes. Genetic predisposition to higher SBP and DBP was associated with increased risk of coronary artery disease (CAD), myocardial infarction (MI), stroke, heart failure (HF), atrial fibrillation (AF), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). Genetically proxied SBP exclusively was associated with CAD (OR 1.18, 95% CI: 1.03–1.36, per 10 mmHg), stroke (1.44[1.28–1.62]), ischemic stroke (1.49[1.30–1.69]), HF (1.41[1.20–1.65]), AF (1.28[1.15–1.43]), and T2DM (1.2[1.13–1.46]). Genetically proxied DBP exclusively was associated with stroke (1.21[1.06–1.37], per 5 mmHg), ischemic stroke (1.24[1.09–1.41]), stroke small-vessel (1.35[1.10–1.65]) and CAD (1.19[1.00–1.41]). Multivariable MR using exclusive SBP and DBP instruments showed the predominant effect of SBP on CAD (1.23[1.05–1.44], per 10 mmHg), stroke (1.39[1.20–1.60]), ischemic stroke (1.44[1.25–1.67]), HF (1.42[1.18–1.71]), AF (1.26[1.10–1.43]) and T2DM (1.31[1.14–1.52]). The discrepancy between effects of SBP and DBP on outcomes warrants further studies on underpinning mechanisms which may be amenable to therapeutic targeting.

Association of ambient temperature and acute heart failure with preserved and reduced ejection fraction.

Evidence on the association between ambient temperature and the onset of acute heart failure (AHF) is scarce and mixed. We sought to investigate the incidence of AHF admissions based on ambient temperature change, with particular interest in detecting the difference between AHF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). Individualized AHF admission data from January 2015 to December 2016 were obtained from a multicentre registry (Tokyo CCU Network Database). The primary event was the daily number of admissions. A linear regression model, using the lowest ambient temperature as the explanatory variable, was selected for the best-estimate model. We also applied the cubic spline model using five knots according to the percentiles of the distribution of the lowest ambient temperature. We divided the entire population into HFpEF+HFmrEF and HFrEF for comparison. In addition, the in-hospital treatment and mortality rates were obtained according to the interquartile ranges (IQRs) of the lowest ambient temperature (IQR1 <5.5°C; IQR25.5-13.3°C; IQR3 13.3-19.7°C; and IQR4 >19.7°C). The number of admissions for HFpEF, HFmrEF and HFrEF were 2736 (36%), 1539 (20%), and 3354 (44%), respectively. The lowest ambient temperature on the admission day was inversely correlated with the admission frequency for both HFpEF+HFmrEF and HFrEF patients, with a stronger correlation in patients with HFpEF+HFmrEF (R2 =0.25 vs. 0.05, P<0.001). In the sensitivity analysis, the decrease in the ambient temperature was associated with the greatest incremental increases in HFpEF, followed by HFmrEF and HFrEF patients (3.5% vs. 2.8% vs. 1.5% per -1°C, P<0.001), with marked increase in admissions of hypertensive patients (systolic blood pressure >140mmHg vs. 140-100mmHg vs. <100mmHg, 3.0% vs. 2.0% vs. 0.8% per -1°C, P for interaction <0.001). A mediator analysis indicated the presence of the mediator effect of systolic blood pressure. The in-hospital mortality rate (7.5%) did not significantly change according to ambient temperature (P=0.62). Lower ambient temperature was associated with higher frequency of AHF admissions, and the effect was more pronounced in HFpEF and HFmrEF patients than in those with HFrEF.

The Causal Effect of Systolic Blood Pressure Lowering on Vascular Outcomes in Diabetes: A Mendelian Randomization Study.

The effect of lowering systolic blood pressure (SBP) on clinical outcomes in diabetic patients is controversial. We used 2-sample mendelian randomization (MR) to study the causal effect of decreasing SBP on the risk of macrovascular and microvascular outcomes in diabetic patients. We used 362 SBP-related genetic variants from a large genome-wide association study (n = 299 024) and UK Biobank (n = 375 256) as exposure. We evaluated 5 macrovascular and microvascular complications up to 60 742 cases as outcomes in diabetes, including coronary artery disease (CAD), peripheral artery disease (PAD), nephropathy, retinopathy, and composite complications. All cases were diagnosed together with diabetes. We performed follow-up analyses by conducting 7 sensitivity analyses and comparing the present MR with results in general population, and clinical trials. Genetic predisposition of each 10-mm Hg SBP decrease was significantly associated with a 28% decreased risk of CAD (odds ratio [OR]: 0.72; 95% CI, 0.59-0.89; P = .002), a 34% decreased risk of nephropathy (OR: 0.66; 95% CI, 0.54-0.81; P < .001), and a 34% decreased risk of the composite complications (OR: 0.66; 95% CI, 0.58-0.76; P < .001), and was nominally associated with a decreased risk of PAD (OR: 0.69; 95% CI, 0.48-0.99) and retinopathy (OR: 0.90; 95% CI, 0.81-0.99). The MR results in diabetes were similar with that in the general population and clinical trials. SBP lowering was causally associated with an attenuated risk of diabetic CAD and nephropathy. It provides genetic evidence for the beneficial effect of lifelong SBP control in preventing diabetes-related vascular outcomes.

Abstract P032: Initiating Hypertension Treatment To Prevent Incident Cardiovascular Disease: A Population Estimate Using The Cardiovascular Disease Policy Model

Background: Hypertension is a leading preventable cause of CHD, stroke, and heart failure (HF). WHO hypertension guidelines recommend initiating first dose medication in hypertensive adults with access to healthcare, yet many US adults with a usual source of care are not receiving treatment. We estimate the population impact of initiating hypertensive therapy in untreated US adults with uncontrolled blood pressure (BP) and access to usual healthcare on incident CVD. Methods: We used the CVD Policy Model, a dynamic state-transition model of CVD risk factors, events, and outcomes to simulate the impact over 10 years of treating uncontrolled BP in our target population of US adults 35-94 years of age with no prior CVD, baseline systolic BP ≥140mmHg, and no current hypertensive medication use, estimated from National Health and Nutrition Examination Survey years 2015-2018. We initiated first dose medication in the target population reporting access to a usual source of healthcare and at least two visits per year. We used the Law, Morris and Wald equation to estimate the systolic BP effect size for a standard first dose of medication. Results: Initiating hypertension medications in those with currently untreated but with regular healthcare access would prevent 214,000 incident CVD events in the US, a quarter of which (52,000) are incident heart failure (Table 1). First dose treatment (and maintenance) would be expected to reduce incident CHD by 9.1%, HF by 6.1%, ischemic stroke by 8.1%, and hemorrhagic stroke by 11.3% over the decade, compared to no treatment. Treatment of hypertension would have the greatest relative benefit in the prevention on incident CVD events in those younger than 65, compared with those over 65 years of age. Conclusion: In the US population with regular access to healthcare, initiating first dose medications for hypertension in those with elevated blood pressure but currently untreated would reduce incident CVD in both sexes and all age groups, with particular benefit for prevention in those less than 65 years of age.

Associations between increased circulating endothelial progenitor cell levels and anxiety/depressive severity, cognitive deficit and function disability among patients with major depressive disorder

The association of major depressive disorder (MDD) with cardiovascular diseases (CVDs) through endothelial dysfunction is bidirectional. Circulating endothelial progenitor cells (cEPCs), essential for endothelial repair and function, are associated with risks of various CVDs. Here, the relationship of cEPC counts with MDD and the related clinical presentations were investigated in 50 patients with MDD and 46 healthy controls. In patients with MDD, a battery of clinical domains was analysed: depressed mood with Hamilton Depression Rating Scale (HAMD) and Montgomery–Åsberg Depression Rating Scale (MADRS), anxiety with Hamilton Anxiety Rating Scale (HAMA), cognitive dysfunction and deficit with Digit Symbol Substitution Test (DSST) and Perceived Deficits Questionnaire-Depression (PDQ-D), somatic symptoms with Depressive and Somatic Symptom Scale (DSSS), quality of life with 12-Item Short Form Health Survey (SF-12) and functional disability with Sheehan Disability Scale (SDS). Immature and mature cEPC counts were measured through flow cytometry. Increased mature and immature cEPC counts were significantly associated with higher anxiety after controlling the confounding effect of systolic blood pressure, and potentially associated with more severe depressive symptoms, worse cognitive performance and increased cognitive deficit, higher social disability, and worse mental health outcomes. Thus, cEPCs might have pleiotropic effects on MDD-associated symptoms and psychosocial outcomes.

Impact of low-fat and full-fat dairy foods on fasting lipid profile and blood pressure: exploratory endpoints of a randomized controlled trial

Dietary guidelines traditionally recommend low-fat dairy because dairy's high saturated fat content is thought to promote cardiovascular disease (CVD). However, emerging evidence indicates that dairy fat may not negatively impact CVD risk factors when consumed in foods with a complex matrix. The aim was to compare the effects of diets limited in dairy or rich in either low-fat or full-fat dairy on CVD risk factors. In this randomized controlled trial, 72 participants with metabolic syndrome completed a 4-wk run-in period, limiting their dairy intake to ≤3 servings/wk of nonfat milk. Participants were then randomly assigned to 1 of 3 diets, either continuing the limited-dairy diet or switching to a diet containing 3.3 servings/d of either low-fat or full-fat milk, yogurt, and cheese for 12 wk. Exploratory outcome measures included changes in the fasting lipid profile and blood pressure. In the per-protocol analysis (n=66), there was no intervention effect on fasting serum total, LDL, and HDL cholesterol; triglycerides; free fatty acids; or cholesterol content in 38 isolated plasma lipoprotein fractions (P>0.1 for all variables in repeated-measures ANOVA). There was also no intervention effect on diastolic blood pressure, but a significant intervention effect for systolic blood pressure (P=0.048), with a trend for a decrease in the low-fat dairy diet (-1.6±8.6 mm Hg) compared with the limited-dairy diet (+2.5±8.2 mm Hg) in post hoc testing. Intent-to-treat results were consistent for all endpoints, with the exception that systolic blood pressure became nonsignificant (P=0.08). In men and women with metabolic syndrome, a diet rich in full-fat dairy had no effects on fasting lipid profile or blood pressure compared with diets limited in dairy or rich in low-fat dairy. Therefore, dairy fat, when consumed as part of complex whole foods, does not adversely impact these classic CVD risk factors. This trial was registered at clinicaltrials.gov as NCT02663544.

The Effects of Cardiometabolic Factors on the Association Between Serum Uric Acid and Chronic Kidney Disease in Chinese Middle-Aged and Older Population: A Mediation Analysis.

IntroductionTo explore whether dyslipidemia, hyperglycemia or hypertension has mediating effect on the association between serum uric acid (SUA) and the development of chronic kidney disease (CKD).MethodsWe conducted a mediation analysis to explore the potential mediating effects of systolic blood pressure (SBP), diastolic blood pressure (DBP), blood glucose, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) on the association between SUA and estimated glomerular filtration rate (eGFR). The data were obtained from China Health and Retirement Longitudinal Study (CHARLS), covering 5,762 individuals.ResultsSUA had a negative dose-response total effect on eGFR (β -3.11, 95% CI -3.40 to -2.82, P-value<0.001). The linear regression between SUA and seven potential mediators indicated that blood glucose (β 0.80, 95% CI 0.18 to 1.42, P-value=0.012), TG (β 10.01, 95% CI 8.22 to 11.79, P-value<0.001), TC (β 2.64, 95% CI 1.83 to 3.45, P-value<0.001), HDL-C (β -0.27, 95% CI -0.52 to -0.02, P-value=0.034) and LDL-C (β 1.15, 95% CI 0.49 to 1.80, P-value=0.001) all had significant dose-response association with SUA, but SBP and DBP showed no significant association with SUA. In terms of the association between potential mediators and eGFR, only TG (β 0.003, 95% CI -0.001 to 0.01, P-value=0.117) and HDL-C (β 0.01, 95% CI -0.02 to 0.04, P-value=0.444) did not have significant linear association with eGFR. The linear regression showed that SUA was directly associated with eGFR (P-value<0.001).ConclusionsThis study supported that the association between SUA and the risk of CKD was not mediated by hypertension, hyperglycemia or dyslipidemia.

High level systolic blood pressure trajectories is the risk factor for cancer

Objective: To explore the effect of systolic blood pressure (SBP) trajectories on cancers. Methods: The relevant data of 54, 888 employees of Kailuan (Group) Limited Liability Company who participated in the 3 health examinations from 2006-2007, 2008-2009, 2010-2011 were collected and the new onset cancer cases were recorded. The systolic blood pressure trajectory grouping was carried out using the blood pressure measurement values of the 3 physical examinations. The life table method was used to calculate the incidence of cancer, and the multivariate Cox proportional hazard regression model was used to analyze the influence factors of cancer. Results: According to the systolic blood pressure trajectory, 54, 888 subjects were divided into 5 groups, including 14, 326 in the low-stable group, 25, 630 in the moderate-stable group, 5, 390 in the moderate-increasing group, 6, 438 in the elevated-lowering group, and 3, 104 in the elevated-stable group. A total of 1, 070 new onset cancer occurred during the follow-up period of (4.95±0.53) years. The incidence of cancer in the low-stable group, moderate-stable group, moderate-increasing group, elevated-lowering group and elevated-stable group were 1.3% (177/14, 326), 2.2% (491/25, 360), 3.1% (147/5, 390), 2.7% (156/6, 438) and 3.8% (99/3, 104), respectively, the difference was statistically significant (P<0.001). After adjusting for gender, age, smoking, drinking, physical exercise, body mass index (BMI), fasting blood glucose, total cholesterol, antihypertensive drugs, hypoglycemic drugs, and lipid-lowering drugs, multivariate Cox regression analysis showed that the systolic blood pressure trajectory was related to the incidence of cancer. Compared with the low-stable group, the Hazard ratio (HR) in the moderate-stable group, moderate-increasing group, elevated-lowering group and elevated-stable group were 1.413, 1.731, 1.557 and 1.907, respectively (all P<0.001). Conclusion: High systolic blood pressure trajectories is the risk factor for cancer.