Future Hypertension Research Articles

Evidence that Young Normotensive South Asians Show Early Signs of Disturbed Arterial Blood Pressure (ABP) Regulation of in Acute Mental Stress Relative to White Europeans

The risk of cardiovascular disease (CVD) including hypertension is higher in South Asians (SAs) than White Europeans (WEs). But, whether disturbances in autonomic control of the cardiovascular system are present in early adulthood in SAs has not been tested. Thus, we performed studies on young 20 WEs and 21 SAs aged (21.9±0.36, 20.7±0.41 respectively, equal numbers of men and women in each group) in whom arterial blood pressure (ABP), electrocardiogram (ECG), heart rate (HR) and respiration were recorded at rest, during mental stress (3 min Colour Stroop test) and during 5 min slow breathing (6 breaths/min). Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were computed from the pulse contour. Baroreflex sensitivity (BRS) was calculated by the sequence method as change in R-R interval evoked by spontaneous up and down sequences in systolic pressure (SP) at rest and during mental stress and as the relationship between R-R interval and the fall in SP evoked by standing from a squat before and at 0, 3, 6 min following the stress test. HRV was computed in time-domain during mental stress and slow breathing. Comparisons within and between WEs and SAs were done by paired and un-paired t-tests respectively. At rest, WEs and SAs had similar mean ABP (mABP, 86.9±1.42 vs 87.1±1.77mmHg), HR (71.1±2.45 vs 76.2±3.56 beats/min), CO (4.8±0.21 vs 5.2±0.21L/min), SV (76.5±3.86 vs 81.5±2.97ml), TPR (1.14±0.06 vs 1.01±0.04 resistance units), and BRS (up-sequence: 1.2±0.05, down-sequence: 1.2±0.05 vs 1.0±0.09 and 1.2±0.09ms/mmHg). Further, mental stress evoked similar increases in mABP and HR in WEs and SAs but was accompanied by an increase CO in WEs and by an increase in TPR in SAs. Concomitantly, vagal indices of HRV were depressed during mental stress in SAs only (RMSSD: 66.2±7.8 to56.2±11.4 and 67.6±8.7 to 50.0±6.5*ms, *: P<0.05 within WE or SAs). Further during up-sequences in SP, BRS was depressed in both SAs and WEs during mental stress, but during down-sequences, BRS was depressed in WE only (to 0.59±0.10 vs 0.96±0.08*ms/mmHg). Also, following mental stress, BRS during squat to stand, an index of vagosympathetic activity, was depressed in WEs only (0.5±0.04 at rest to 0.3±0.04* vs 0.5±0.06 to 0.5±0.06ms/mmHg). On the other hand, slow breathing, tended to decrease ABP in both WEs and SAs (82.1±1.8 to 79.2±2.1mmHg: P<0.05; 79.4±2.0 to 77.4±2.0mmHg: P=0.09 respectively) and increased vagal indices of HRV in both WEs and SAs (66.3±8.6 to 86.0±13.2*ms; 67.6±8.7 to 86.48.8*ms). These results suggest that during and after mental stress, young normotensive SAs show greater sympathetic vasoconstriction than WEs, and attenuated respiratory modulation of HR, while their ability to evoke baroreflex tachycardia by vagal inhibition and sympathetic activation is preserved relative to young WEs. Such disturbances in would be expected to increase the risk of future CVD and hypertension in SAs, particularly in those with high levels of daily stress. The finding that slow breathing increased vagal activity in young SAs raises the possibility that regular slow breathing may help to normalize autonomic regulation of ABP in SAs and limit future CVD.

Combined Oral Contraceptive Pill-Induced Hypertension and Hypertensive Disorders of Pregnancy: Shared Mechanisms and Clinical Similarities.

Oral contraceptive pill-induced hypertension (OCPIH) and hypertensive disorders in pregnancy (HDP) share common risk factors and pathophysiological mechanisms, yet the bidirectional relationship between these two conditions is not well-established. We review and describe OCPIH and HDP to better understand how hormonal and metabolic imbalances affect hypertension. Oral contraceptive pills continue to be a popular method of contraception, with an incidence of OCPIH ranging from 1-8.5% among OCP users. HDP have an incidence of 5-10% of all pregnancies in the USA and have been shown to be a powerful predictor of lifetime adverse cardiovascular outcomes, including future hypertension. OCPIH and HDP share common risk factors such as age, BMI, past personal and family history of hypertension, as well as pathogenic mechanisms, including alterations in hormonal metabolism and the renin angiotensin aldosterone system; imbalance of vasodilator-vasoconstrictor compounds; and changes in the cardiovascular system. Future research should address additional potential mechanisms that underlie hypertension in these two conditions where endocrine changes, either physiological (pregnancy) or iatrogenic (use of OCP), play a role. This may lead to novel, targeted treatment options to improve hypertension management and overall cardiovascular risk profile management in this subset of young female patients.

Cardiovascular Responses to Submaximal Exercise Stress Test in Adolescents with High Visceral Fatness

Background and Aim: Visceral adiposity per se was associated with risk of developing hypertension in future. There is escalating trend of visceral obesity in Indian adolescents. Nonetheless, the Asian Indian population is known to have an affinity for central fat deposition than peripheral fat. Meanwhile, the association of visceral adiposity and cardiovascular response to exercise in Indian adolescents of 18-19 years’ age group has not been well described so far. Therefore, the present study was undertaken. Methods: A Cross-sectional study was conducted on 120 non-athletes’ (60 males and 60 females) late Indian Adolescents of 18-19 years’ age group. Visceral Fat (VF) and Other Body composition were measured by Bioelectrical Impedance technique using Omron HBF 302 body fat analyzer. The participants were customized into two groups based on their Visceral Fat Level (0-9: Normal VF group; &gt; 9: High VF group). Exercise Testing was done by treadmill exercise test following standard Bruce protocol. Cardiovascular reactivity (Heart Rate, Systolic and Diastolic Blood Pressure) was checked at the end of each stage of Bruce Protocol. Results: Increased SBP and DBP responses to treadmill exercise tests at different stages were seen in high VF groups in both the genders. However, no abnormal reactivity was observed in high VF groups of both the genders. Conclusion: During treadmill exercise stress test, high blood pressure reactivity was seen in high visceral fat adolescents as compared to normal visceral fat adolescents, which was primarily due to their high resting blood pressure. Adolescents with normal visceral fat were competent to cross more number of Bruce stages than high visceral fat Indian adolescents. Visceral fat had a stronger influence on baseline cardiovascular parameters like systolic and diastolic blood pressure as well as blood pressure parameter during exercise than total body fat.

A NEW GENETIC RISK SCORE FOR BLOOD PRESSURE STRONGLY ASSOCIATES WITH THE INCIDENCE OF HYPERTENSION AND CARDIOVASCULAR ENDPOINTS IN TWO SWEDISH COHORTS

Objective: The clinical value of the polygenetic component of blood pressure is commonly questioned. We constructed a new BP-GRS, including the most recently published variants genome wide significantly associated with either systolic or diastolic blood pressure (SBP, DBP), to investigate its association to the incidence of hypertension and cardiovascular endpoints in two urban-based cohorts: the Malmö Diet and Cancer (MDC, n = 29295) and Malmö Preventive Project (MPP, n = 9367). Design and method: The genotyping was performed with the Illumina GWAS chip (GSA array v1) and a weighted BP-GRS858 based on 858 SNPs was calculated, normalized, and divided into deciles. Logistic regression and survival Cox Regression models were used to test the associations of the new BP-GRS858 with outcomes. Results: At baseline, we found a difference of 11.2 mmHg (SBP) and 6 mmHg (DBP) between the top and the bottom deciles of BP-GRS858. In MPP, the top vs bottom decile of BP-GRS858 was associated with a doubled risk of incident hypertension (OR, 95%CI: 2.2, 1.7–2.8, p-value: 2.0E-10). In MDC, when comparing the top and bottom deciles of BP-GRS858, significant association was found between the age and sex adjusted BP-GRS858 and the incidence of total cardiovascular events (HR, 95%CI: 1.5; 1.3–1.7; p-value: 1.5E-12), stroke (HR, 95%CI: 1.6, 1.4–1.8; p-value: 2.1E-9), coronary artery disease (HR, 95%CI: 1.5, 1.4–1.8; p-value:1.3E-11), heart failure (HR, 95%CI: 1.5, 1.3–1.8, p-value: 2.5E-5), atrial fibrillation (HR, 95%CI: 1.2–1.1,1.4; p-value: 0.001) and total mortality (HR, 95%CI: 1.1, 1.0–1.2; p-value: 0.009). Most of these associations remained significant after adjusting for traditional risk factors, including hypertension. Conclusions: Our findings confirm that adding novel genetic variants into a polygenic BP-GRS, despite very low effect sizes of individual variants, increases its predictive performance. GRS858 contributes with clinically meaningful predictive information regarding future hypertension and CVD risk. Given that the exposure to high polygenetic risk starts at birth, we suggest that the BP-GRS858 might be useful to identify children or adolescents who would benefit from early hypertension screening and treatment.

Device Therapy of Hypertension.

In the past decade, efforts to improve blood pressure control have looked beyond conventional approaches of lifestyle modification and drug therapy to embrace interventional therapies. Based upon animal and human studies clearly demonstrating a key role for the sympathetic nervous system in the etiology of hypertension, the newer technologies that have emerged are predominantly aimed at neuromodulation of peripheral nervous system targets. These include renal denervation, baroreflex activation therapy, endovascular baroreflex amplification therapy, carotid body ablation, and pacemaker-mediated programmable hypertension control. Of these, renal denervation is the most mature, and with a recent series of proof-of-concept trials demonstrating the safety and efficacy of radiofrequency and more recently ultrasound-based renal denervation, this technology is poised to become available as a viable treatment option for hypertension in the foreseeable future. With regard to baroreflex activation therapy, endovascular baroreflex amplification, carotid body ablation, and programmable hypertension control, these are developing technologies for which more human data are required. Importantly, central nervous system control of the circulation remains a poorly understood yet vital component of the hypertension pathway and mandates further investigation. Technology to improve blood pressure control through deep brain stimulation of key cardiovascular control territories is, therefore, of interest. Furthermore, alternative nonsympathomodulatory intervention targeting the hemodynamics of the circulation may also be worth exploring for patients in whom sympathetic drive is less relevant to hypertension perpetuation. Herein, we review the aforementioned technologies with an emphasis on the preclinical data that underpin their rationale and the human evidence that supports their use.

CENTRAL SYSTOLIC BLOOD PRESSURE RELATES INVERSELY TO NITRIC OXIDE SYNTHESIS IN YOUNG BLACK ADULTS: THE AFRICAN-PREDICT STUDY

Objective: Lower nitric oxide bioavailabilty associates with hypertension in diseased and elderly populations. With hypertension known to develop earlier in black populations, we compared both plasma and urinary nitric oxide-related markers and their associations with central systolic blood pressure and arterial stiffness in healthy young black and white adults. Design and method: We included healthy black and white men and women (n = 1110; 20–30 years) and measured central systolic blood pressure and pulse wave velocity, along with both plasma and urinary arginine, homoarginine, asymmetric dimethylarginine, symmetric dimethylarginine, as well as urinary ornithine/citrulline, nitrite and nitrate. Additionally, the urinary nitrate-to-nitrite ratio was calculated. Results: The black men and women had higher central systolic blood pressure and higher plasma arginine and asymmetric dimethylarginine, but lower urinary nitrate and urinary nitrate-to-nitrite ratio (all p&lt; = 0.003) than their white counterparts. In single and forward stepwise multiple regression analyses, we found an inverse association of central systolic blood pressure (adj. R2 = 0.124; β= –0.134; p = 0.006) and plasma homoarginine in black men. Central systolic blood pressure associated inversely with urinary nitrate-to-nitrite ratio in black women only (adj. R2 = 0.171; β= –0.130; p = 0.029). In the white women, central systolic blood pressure associated positively with urinary asymmetric dimethylarginine (adj. R2 = 0.372; β= 0.162; p = 0.015). Pulse wave velocity associated inversely with plasma asymmetric dimethylarginine (adj. R2 = 0.253; β= –0.163; p = 0.024) in the white women only. Conclusions: The lower nitric oxide synthesis and the higher central systolic blood pressure in our black cohort support the notion of a potential increased risk for future large artery stiffness and hypertension development in later life.

AQUAPORIN-3 AND CYBA GENETIC POLYMORPHISMS MAY PREDICT RISK OF DEVELOPING HYPERTENSION

Objective: Preeclampsia, a placentation disorder, affects 7% of pregnancies in Europe. It influences future cardiovascular disease, such as hypertension. Preeclampsia and hypertension have been associated with oxidative stress, therefore, key proteins in redox signaling may be involved with the development of hypertensive disorders during/after pregnancy. This study aimed at determining associations between oxidative stress-related gene polymorphisms (AQP3-rs2231231 and CYBA-rs4673) with the development of preeclampsia and the risk for future hypertension. Design and method: A cohort of 150pregnant Caucasian women, aged 35.24 ± 5.47 years, 60(40%) normotensive and 90(60%) preeclamptic, was evaluated. Based on a prospective study(2–16 years later), these women were evaluated for the development of hypertension and classified as normotensive 98(67%) or hypertensive 48(33%). The influence of genetic polymorphisms on the susceptibility for cardiovascular disease was evaluated. In this cohort, anthropometric/haemodynamic parameters were studied. For statistical analysis chi-square and Student t-test were used. Results: During pregnancy, no differences between the distribution of studied genetic polymorphisms in preeclampsia were found. However, based on the AQP3 dominant model of A, our data showed that AA+AC genotypes were more frequent (73.3%;p = 0.014) in hypertensive individuals. Moreover, allele A, the allele of risk, was associated with a 3.405-fold higher risk (p = 0.016,OR = 3.405,95%CI[1.26–9.19]) to develop hypertension after pregnancy. In addition, a higher systolic(p = 0.017) and diastolic(p = 0.008) pressure were also observed in women carrying the AA+AC genotype. Furthermore, based on CYBA dominant model of C, TT genotype of polymorphism was also correlated with the development of hypertension(100.0%;p = 0.007) after pregnancy. On the other hand, looking at the recessive model of C, CT+TT genotype was associated with the development of hypertension. Allele T, the allele of risk, was associated with 6.5-fold risk (p = 0,024,OR = 6.500,95%CI[1.28–33.03] to develop hypertension. Moreover, CT+TT genotypes of CYBA genetic polymorphism were more associated with increased weight (p = 0.014), higher waist circumference(p = 0.010), hip(p = 0.008) and systolic(p &lt; 0.001) and diastolic blood pressure(p &lt; 0.001). Conclusions: In this study, AQP3 genetic polymorphism was found associated with the hypertensive disorders after pregnancy for the first time. In addition, CYBA was also associated with the development of essential hypertension. These results open new perspectives in the development of new approaches for cardiovascular disease prevention.

Biological Pathways in Adolescent Aortic Stiffness.

BackgroundAortic stiffening begins in youth and antedates future hypertension. In adults, excess weight, systemic inflammation, dyslipidemia, insulin resistance, neurohormonal activation, and altered adipokines are implicated in the pathogenesis of increased aortic stiffness. In adolescents, we assessed the relations of comprehensive measures of aortic stiffness with body mass index (BMI) and related but distinct circulating biomarkers.Methods and ResultsA convenience sample of 246 adolescents (mean age, 16±2 years; 45% female, 24% Black, and 43% Hispanic) attending primary care or preventive cardiology clinics at 2 tertiary hospitals was grouped as normal weight (N=98) or excess weight (N=148, defined as BMI ≥age‐ and sex‐referenced 85th percentile). After an overnight fast, participants underwent anthropometry, noninvasive arterial tonometry, and assays for serum lipids, CRP (C‐reactive protein), glucose, insulin, renin, aldosterone, and leptin. We used multivariable linear regression to relate arterial stiffness markers (including carotid‐femoral pulse wave velocity) to BMI z score and a biomarker panel. Carotid‐femoral pulse wave velocity was higher in excess weight compared with normal weight group (5.0±0.7 versus 4.6±0.6 m/s; P<0.01). After multivariable adjustment, carotid‐femoral pulse wave velocity was associated with BMI z score (0.09 [95% CI, 0.01–0.18]; P=0.04) and with low‐density lipoprotein cholesterol (0.26 [95% CI, 0.03–0.50]; P=0.03).ConclusionsHigher BMI and low‐density lipoprotein cholesterol were associated with greater aortic stiffness in adolescents. Maintaining optimal BMI and lipid levels may mitigate aortic stiffness.

Association of Aquaporin-3, Aquaporin-7, NOS3 and CYBA polymorphisms with hypertensive disorders in women.

Preeclampsia (PE), a pregnancy disorder influenced by oxidative stress and hypoxia, affects the health of the mother and baby and is associated with an increased risk of future hypertension (HT). Aquaporins are a family of water channels, comprising members that also transport glycerol (aquaglyceroporins) and hydrogen peroxide (peroxiporins), key molecules for metabolic homeostasis and redox signaling. Here, we investigated the association of Aquaporin-3 (AQP3; rs2231231), Aquaporin-7 (AQP7; rs2989924), NOS3 (4B/A intron) and CYBA (rs4673) genetic polymorphisms with the development of hypertensive disorders by qPCR/PCR in a cohort of 150 normotensive (NT) women (N=90) or with previous PE (N=60) during pregnancy. Prospectively, women were reclassified 2-16years after pregnancy as NT (N=98) or hypertensive (N=48) and the genetic associations were reevaluated. In addition, genetic associations were reevaluated and compared between normotensive and hypertensive (HT) subjects. We found that AQP3 rs2231231, an aquaglyceroporin/peroxiporin, is associated with the development of HT, whereas AQP7, NOS3 and CYBA polymorphism did not correlate with PE or future HT. Because AQP3 was associated with hypertension only after pregnancy, its role might be related to later risk factors of hypertension such as metabolic syndrome or oxidative stress.

Fitness, waist circumference and their association with future blood pressure in youth: The UP&DOWN Longitudinal Study

ObjectivesThe aim was to determine the independent associations of muscular fitness (MF), cardiorespiratory fitness (CRF) and waist circumference (WC) with blood pressure (BP) levels over 2 years in children and adolescents. Methods1089 children (517 females) and 787 adolescents (378 females) with complete data on fitness, WC and BP (systolic [SBP] and diastolic [DBP]) were included. Upper MF was assessed through the handgrip strength test, and lower MF using the standing long jump test. The 20-m shuttle run test was used to assess CRF. WC was obtained following standardized methods. Different regression models were fitted by introducing fitness and WC at baseline and their changes as exposures and BP at follow-up and their changes as outcomes. ResultsWC at baseline was positively and independently associated with each BP variable at follow-up in children and adolescents (β=0.094–0.260; p≤0.05), and CRF was negatively associated with DBP in adolescents (β=−0.096; p=0.034). WC changes were associated with BP variables 2 years later in children (β=0.121–0.142; p<0.01). In adolescents, changes in upper MF (β=−0.116; p=0.001) and WC (β=0.080–0.098; p<0.05) were associated with SBP at follow-up. WC changes were independently associated with changes in each BP variable in children (β=0.111–0.145; all p<0.05) and SBP changes in adolescents (β=0.103 to 0.117; all p<0.01). ConclusionsWC, but neither MF nor CRF, is independently associated with BP and its changes over 2 years. The attainment or maintenance of optimal fatness levels in the pediatric population should be highly encouraged for the prevention of future hypertension.

Reduced heart-rate variability and increased risk of hypertension-a prospective study of the ELSA-Brasil.

Although autonomic disturbances are known to precede hypertension onset, the risks underlying different ranges of blood pressure and impaired cardiac autonomic modulation are still unknown. This study aimed to identify the risk of hypertension incidence related to low heart-rate variability profile in normotensive blood pressure subcategories: normal (<120/80 mmHg) and prehypertension (120/80-139/89 mmHg) in a 4-year follow-up. 7665 participants free of hypertension at baseline were examined. They were allocated into one of two groups (<P25 and ≥P25) based on age-specific value distributions of heart-rate variability ranges presented in the literature. The relationship between heart-rate variability parameters (SDNN, RMSSD, VLF, LF, and HF) and hypertension incidence was analyzed using Poisson regression. The reference for the independent variable in these regressions was the dataset with all HRV values ≥P25. After full adjustments for age, sex, ethnicity, educational level, body mass index, smoking status, glucose, insulin, dyslipidemia, alcohol consumption, and physical activity, low values for all heart-rate variability indices were significantly associated with an increased relative risk of developing hypertension in the overall sample. Individuals with normal BP levels presented an increased risk for low SDNN, VLF, and LF values, whereas the risk in prehypertensive participants was only verified for low VLF. In conclusion, cardio autonomic disturbances precede the incidence of clinical hypertension and are potentially involved in its pathophysiological basis and progression. Even individuals with normal blood pressure may be at an increased risk for future hypertension in the presence of reduced cardio autonomic control.

Clinical Evaluation of the Polygenetic Background of Blood Pressure in the Population-Based Setting.

The clinical value of the polygenetic component of blood pressure (BP) is commonly questioned. We evaluated a genetic risk score for BP (BP-GRS858), based on the most recently published genome-wide association studies variants that were significantly associated with either systolic BP or diastolic BP, for prediction of hypertension and cardiovascular end points. The genotyping was performed in 2 urban-based prospective cohorts: the Malmö Diet and Cancer (n=29 295) and the Malmö Preventive Project (n=9367) and a weighted BP-GRS858 based on 858 SNPs was calculated. At baseline, we found a difference of 9.0 mm Hg (systolic BP) and 4.8 mm Hg (diastolic BP) between the top and the bottom quartile of BP-GRS858. In Malmö Preventive Project, the top versus bottom quartile of BP-GRS858 was associated with a doubled risk of incident hypertension (odds ratio, 2.05 [95% CI, 1.75-2.39], P=1.4×10-21), a risk higher than that of body mass index, as evaluated in quartiles. In Malmö Diet and Cancer, significant association was found between the age and sex-adjusted BP-GRS858 and the incidence of total cardiovascular events, stroke, coronary artery disease, heart failure, atrial fibrillation, and total mortality. Most of these associations remained significant after adjusting for traditional risk factors, including hypertension. BP-GRS858 could contribute predictive information regarding future hypertension, with an effect size comparable to other well-known risk factors such as obesity, and predicts cardiovascular events. Given that the exposure to high polygenetic risk starts at birth, we suggest that the BP-GRS858 might be useful to identify children or adolescents who would benefit from early hypertension screening and treatment.

Characteristics, anticoagulation, and outcomes of portal vein thrombosis after intra-abdominal surgery

BackgroundIntra-abdominal surgery is a cause of portal vein thrombosis; however, postsurgical portal vein thrombosis has not been extensively described. MethodsThis is a retrospective study of 107 patients with postsurgical portal vein thrombosis followed for a median 25 months (interquartile range 11–51). Outcomes were complete radiographic resolution of portal vein thrombosis and development of clinical portal hypertension. ResultsSurgeries associated with portal vein thrombosis included colectomy (n = 42), bariatric surgery (n = 25), and splenectomy (n = 11). Presentations were nonspecific, typically characterized by abdominal pain. Sixty-three patients (59%) achieved complete radiographic resolution. On univariable analysis, provoking surgery, occlusivity of portal vein thrombosis, and anticoagulant used were associated with complete radiographic resolution. Colectomy was associated with a complete radiographic resolution rate of 30/42 (71%), bariatric 10/25 (40%), splenectomy 2/11 (18%), and other 21/29 (72%), (log rank P = .0033). Nonocclusive thrombus was associated with a complete radiographic resolution rate of 44/62 (71%), occlusive thrombus 19/45 (42%), (log rank P = .0101). Direct oral anticoagulants were associated with a complete radiographic resolution rate of 27/35 (77%), enoxaparin 20/29 (69%), warfarin 14/31 (45%), and no anticoagulant 2/12 (17%), (log rank P = .0002). On multivariable analysis, only anticoagulant choice was significantly associated with complete radiographic resolution. Using direct oral anticoagulants as reference, no anticoagulant yielded an adjusted hazard ratio of 0.10 for complete radiographic resolution (95% confidence interval 0.023–0.44), warfarin 0.40 (95% confidence interval 0.20–0.78), and enoxaparin 0.64 (95% confidence interval 0.49–1.60). Failure to achieve complete radiographic resolution was associated with greater risk of future clinical portal hypertension. Twenty-three patients (21%) went on to develop clinical portal hypertension; 20 who failed to achieve complete radiographic resolution (45%), and only 3 who achieved complete radiographic resolution (5%), (log rank P < .0001). ConclusionThe natural history of postsurgical portal vein thrombosis is variable and influenced by type of surgery, degree of occlusion, and, most notably, type of anticoagulant used. Failure to recanalize the portal vein carries considerable risk of future clinical portal hypertension.

Joint Associations of Maternal-Fetal APOL1 Genotypes and Maternal Country of Origin With Preeclampsia Risk

Preeclampsia, which disproportionately affects Black women, is a leading cause of preterm delivery and risk for future hypertension and chronic kidney disease (CKD). Apolipoprotein L1 (APOL1) kidney risk alleles, common among Black individuals, contribute substantially to CKD disparities. Given the strong link between preeclampsia and CKD, we investigated whether maternal and fetal APOL1 risk alleles can jointly influence preeclampsia risk, and explored potential modifiers of the association between APOL1 and preeclampsia. Nested case-control study. 426 Black mother-infant pairs (275 African Americans and 151 Haitians) from the Boston Birth Cohort. Maternal and fetal APOL1 risk alleles. Preeclampsia. Logistic regression models with adjustment for demographic characteristics were applied to analyze associations between fetal and maternal APOL1 risk alleles and risk of preeclampsia and to investigate the effects of modification by maternal country of origin. Fetal APOL1 risk alleles tended to be associated with an increased risk of preeclampsia, which was not statistically significant in the total genotyped population. However, this association was modified by maternal country of origin (P<0.05 for interaction tests): fetal APOL1 risk alleles were significantly associated with an increased risk of preeclampsia among African Americans under recessive (odds ratio [OR], 3.6 [95% CI, 1.3-9.7]; P=0.01) and additive (OR, 1.7 [95% CI, 1.1-2.6]; P=0.01) genetic models but not in Haitian Americans. Also, maternal-fetal genotype discordance at the APOL1 locus was associated with a 2.6-fold higher risk of preeclampsia (P<0.001) in African Americans. Limited sample size in stratified analyses; self-reported maternal country of origin; pre-pregnancy estimated glomerular filtration rate (eGFR) and proteinuria data in mothers were not collected; unmeasured confounding social and/or environmental factors; no replication study. This study supports the hypothesis that fetal APOL1 kidney risk alleles are associated with increased risk for preeclampsia in a recessive mode of inheritance in African Americans and suggests that maternal-fetal genotype discordance is also associated with this risk. These conclusions underscore the need to better understand maternal-fetal interaction and their genetic and environmental factors as contributors to ethnic disparities in preeclampsia.

Dietary fat and alcohol in the prediction of indices of vascular health among young adults

ObjectivesArterial stiffness, particularly of the aorta, is an independent predictor of future cardiovascular disease, all-cause mortality, and hypertension. Arterial stiffening may be caused or exacerbated by the composition of the diet. Current research has indicated that habitual dietary patterns may influence arteriosclerosis, or the thickening and hardening of the artery walls, but has yet to identify a specific food group as the culprit. In young, college-aged adults, dietary fat intake and alcohol consumption tend to be higher compared to other periods throughout the life cycle. Therefore, the purpose of this study was to determine the influence of dietary fat and alcohol consumption on the vascular health of apparently healthy young adults. MethodsThe data collected were assessed to determine if dietary fat and alcohol in young (18–30 y), college-aged adults (n = 50) were independent predictors of an increase in arterial stiffening. Vascular health was determined by the carotid-femoral pulse-wave velocity and the augmentation index corrected for a heart rate of 75 beats/min; dietary patterns were assessed using the Dietary Health Questionnaire II. ResultsThe gold standard marker of aortic stiffness, carotid femoral pulse-wave velocity, was positively correlated with cheese consumption (R2 = 0.092, P = 0.033), alcohol consumption (R2 = 0.102, P = 0.024), and total energy/calories (%) from alcohol (R2 = 0.118, P = 0.015) in univariate analysis. In forward-selection multiple regression analysis, energy from alcohol and cheese consumption accounted for 23.7% of the variance in carotid-femoral pulse-wave velocity (P = 0.009). The augmentation index wave reflection marker was positively correlated with total dietary fat (R2 = 0.110, P = 0.019), trans fatty acids (R2 = 0.092, P = 0.032), saturated fatty acids (R2 = 0.124, P = 0.012), monounsaturated fatty acids (R2 = 0.012, P = 0.015), red-meat consumption (R2 = 0.094, P = 0.030), and discretionary fat from solids in univariate analysis (R2 = 0.137, P = 0.008). Discretionary fat from solids accounted for 13.7% of the variation in augmentation index in forward-selection multiple regression analysis (P = 0.008). ConclusionsThese results indicate the potential roles of dietary fat and alcohol consumption in early vascular aging by stiffening the arteries of young, college-aged adults, which may in turn contribute to future adverse cardiovascular disease outcomes.

Central systolic blood pressure relates inversely to nitric oxide synthesis in young black adults: the African-PREDICT study.

Lower nitric oxide (NO) bioavailabilty associates with hypertension in patients and elderly populations. With hypertension known to develop earlier in black populations, we compared both plasma and urinary NO-related markers and their associations with central systolic blood pressure (cSBP) and arterial stiffness in healthy young black and white adults. We included healthy black and white men and women (n = 1110; 20-30 years) and measured cSBP and pulse wave velocity (PWV), along with both plasma and urinary arginine, homoarginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), as well as urinary ornithine/citrulline, nitrite and nitrate. In addition, the urinary nitrate-to-nitrite ratio (UNOxR) was calculated. The black men and women had higher cSBP and higher plasma arginine and ADMA, but lower urinary nitrate and UNOxR (all p ≤ 0.003) than their white counterparts. In single and forward stepwise multiple regression analyses, we found an inverse association of cSBP (adj. R2 = 0.124; β = -0.134; p = 0.006) and plasma homoarginine in black men. Central SBP associated inversely with UNOxR in black women only (adj. R2 = 0.171; β = -0.130; p = 0.029). In the white women, cSBP associated positively with urinary ADMA (adj. R2 = 0.372; β = 0.162; p = 0.015). PWV associated inversely with plasma ADMA (adj. R2 = 0.253; β = -0.163; p = 0.024) in the white women only. The lower NO synthesis and the higher cSBP in our black cohort support the notion of a potential increased risk for future large artery stiffness and hypertension development in later life.

The prevalence of hypertension and its distribution by sociodemographic factors in Central Mozambique: a cross sectional study

BackgroundHypertension (HTN) is a major risk factor for cardiovascular diseases, and its prevalence has been rising in low- and middle-income countries. The current study describes HTN prevalence in central Mozambique, association between wealth and blood pressure (BP), and HTN monitoring and diagnosis practice among individuals with elevated BP.MethodsThe study used data from a cross-sectional, representative household survey conducted in Manica and Sofala provinces, Mozambique. There were 4101 respondents, aged ≥20 years. We measured average systolic and diastolic BP (SBP and DBP) from three measurements taken in the household setting. Elevated BP was defined as having either SBP ≥140 or DBP ≥90 mmHg.ResultsThe mean age of the participants was 36.7 years old, 59.9% were women, and 72.5% were from rural areas. Adjusting for complex survey weights, 15.7% (95%CI: 14.0 to 17.4) of women and 16.1% (13.9 to 18.5) of men had elevated BP, and 7.5% (95% CI: 6.4 to 8.7) of the overall population had both SBP ≥140 and DBP ≥90 mmHg. Among participants with elevated BP, proportions of participants who had previous BP measurement and HTN diagnosis were both low (34.9% (95% CI: 30.0 to 40.1) and 12.2% (9.9 to 15.0) respectively). Prior BP measurement and HTN diagnosis were more commonly reported among hypertensive participants with secondary or higher education, from urban areas, and with highest relative wealth. In adjusted models, wealth was positively associated with higher SBP and DBP.ConclusionsThe current study found evidence of positive association between wealth and BP. The prevalence of elevated BP was lower in Manica and Sofala provinces than the previously estimated national prevalence. Previous BP screening and HTN diagnosis were uncommon in our study population, especially among rural residents, individuals with lower education levels, and those with relatively less wealth. As the epidemiological transition advances in Mozambique, there is a need to develop and implement strategies to increase BP screening and deliver appropriate clinical services, as well as to encourage lifestyle changes among people at risk of developing hypertension in near future.

Safety evaluation of high-dose intake of casein-derived peptide Met-Lys-Pro in healthy adults: A randomized, double-blind, placebo-controlled trial.

Met‐Lys‐Pro (MKP) is a casein‐derived angiotensin I‐converting enzyme inhibitory peptide with the potential to cross the blood–brain barrier. It has shown preventive effects against high blood pressure (BP) and cognitive decline in animal models and human studies. MKP shows good water solubility and can be blended into a variety of foods. However, its ease of intake may contribute to the possibility of overdose. Therefore, we aimed to evaluate the safety of high‐dose intake of MKP in healthy adults by conducting a randomized controlled trial with 30 subjects. Participants were randomly allocated to the MKP (n = 15) or placebo (n = 15) group. Over 4 weeks, the MKP group received test powder containing a daily dose of 1,000 μg of MKP, five times the minimum effective dose for cognitive improvement, whereas the placebo group received dextrin powder containing no detectable MKP. No clinical problems were observed in anthropometric and BP measurements or in blood and urine parameters. No adverse events owing to MKP intake were observed. These findings suggest that consumption of MKP is safe, and that it may be applicable as a safe preventive measure against hypertension and cognitive decline in future.

Resting Heart Rate as a Cardiovascular Risk Factor in Hypertensive Patients: An Update.

A large body of evidence has shown that resting heart rate (RHR) holds important prognostic information in several clinical conditions. In the majority of the general population studies, a graded association between RHR and mortality from all causes, cardiovascular (CV) disease, ischemic heart disease, and stroke has been observed. These associations appeared even stronger and more consistent in hypertensive patients. Studies performed with 24-hour ambulatory recording have shown that an elevated nighttime heart rate may confer an additional risk on top of office RHR. The mechanisms by which tachycardia alone or in association with sympathetic overactivity induces CV damage are well understood. Fast RHR is a strong predictor of future hypertension, metabolic disturbances, obesity, and diabetes. Several experimental lines of research point to high RHR as a main risk factor for the development of atherosclerosis, large artery stiffness, and CV disease. Elevated RHR is a common feature in patients with hypertension. Thus, there is a large segment of the hypertensive population that would benefit from a treatment able to decrease RHR. Improvement of unhealthy lifestyle should be the first goal in the management of the hypertensive patient with elevated RHR. Most clinical guidelines now recommend the use of combination therapies even in the initial treatment of hypertension. Although no results of clinical trials specifically designed to investigate the effect of RHR lowering in human beings without CV diseases are available, in hypertensive patients with high RHR a combination therapy including a cardiac slowing drug at optimized dose seems a sensible strategy. Tachycardia can be considered both as a marker of sympathetic overactivity and as a risk factor for cardiovascular events. In this sketch, the main cardiovascular and metabolic effects of increased sympathetic tone underlying high heart rate are shown. The link between tachycardia and cardiovascular events can be explained also by the direct hemodynamic action of heart rate on the arteries and the left ventricular (LV) wall.

Cancer and Cardiovascular Risk in Women With Hypertensive Disorders of Pregnancy Carrying a Common IGF1R Variant

ObjectiveTo evaluate the impact of insulin-like growth factor 1 receptor variant rs2016347 on the risk for breast and nonbreast cancers and cardiovascular disease in women with a history of hypertensive disorders of pregnancy (HDP). Patients and MethodsThis retrospective cohort study included all parous women in the UK Biobank with prior rs2016347 genotyping (N=204,155), with enrollment taking place from March 2006 to July 2010. History of HDP was self-reported, and outcomes included breast and all nonbreast cancers, hospital diagnoses of hypertension and cardiovascular disease, and direct blood pressure measurements. ResultsWomen with previous HDP had a higher risk for future hypertension and cardiovascular diagnoses, increased blood pressures, and lower risk for breast cancer compared with women without HDP, consistent with prior studies. Hazard ratios for all nonbreast cancers were unchanged. However, when taking genotype into account, HDP-positive women carrying at least 1 thymine (T) allele of rs2016347 had a lower risk for nonbreast cancer (hazard ratio, 0.59; 95% CI, 0.37 to 0.92; P=.02) and lower systolic blood pressure (−2.08±0.98 mm Hg; P=.03) compared with women with the guanine/guanine (GG) genotype with positive evidence of interaction (HDP:T allele) for both outcomes; P=.04 and P=.03, respectively. ConclusionWomen who experience HDP and carry a T allele of rs2016347 have 41% lower risk for developing nonbreast cancer and a lower systolic blood pressure of 2.08 mm Hg when compared with those with the GG genotype, suggesting a possible role of the insulin-like growth factor 1 axis for both cardiovascular and cancer risk in women with HDP.