Arteriosclerosis, Atherosclerosis, and Cardiovascular Health: Joint Relations to the Incidence of Cardiovascular Disease.

[Figure: see text].

A patient with Silver-Russell syndrome with multilocus imprinting disturbance, and Schimke immuno-osseous dysplasia unmasked by uniparental isodisomy of chromosome 2.

Silver-Russell syndrome (SRS) is a congenital disorder characterized by prenatal and postnatal growth failure and craniofacial features. Hypomethylation of the H19/IGF2:IG-differential methylated region (H19LOM) is observed in 50% of SRS patients, and 15% of SRS patients with H19LOM had multilocus imprinting disturbance (MLID). Schimke immuno-osseous dysplasia (SIOD), characterized by spondyloepiphyseal dysplasia and nephropathy, is an autosomal recessive disorder caused by mutations in SMARCAL1 on chromosome 2. We report a patient with typical SRS-related features, spondyloepiphyseal dysplasia, and severe nephropathy. Molecular analyses showed H19LOM, paternal uniparental isodisomy of chromosome 2 (iUPD(2)pat), and a paternally inherited homozygous frameshift variant in SMARCAL1. Genome-wide methylation analysis showed MLID in this patient, although it showed no MLID in another patient with SIOD without SRS phenotype. These results suggest that iUPD(2)pat unmasked the recessive mutation in SMARCAL1 and that the SMARCAL1 gene mutation may have no direct effect on the patient's methylation defects.

Arteriosclerose, aterosclerose, arteriolosclerose e esclerose calcificante da média de Monckeberg: qual a diferença? / Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg medial calcific sclerosis: what is the difference?

Resumo A principal causa de óbito na contemporaneidade são as doenças cardiovasculares. Arteriosclerose, aterosclerose, arteriolosclerose e arteriosclerose de Monckeberg são termos frequentemente utilizados como sinônimos, mas traduzem alterações distintas. O objetivo desta revisão foi discutir os conceitos de arteriosclerose, aterosclerose, arteriolosclerose e esclerose calcificante da média de Monckeberg. O termo arteriosclerose é considerado mais genérico, significando o enrijecimento e a consequente perda de elasticidade da parede arterial, abarcando os demais tipos. A aterosclerose é uma doença inflamatória secundária a lesões na camada íntima, que tem como principal complicação obstrução crônica e aguda do lúmen arterial. A arteriolosclerose se refere ao espessamento das arteríolas, particularmente relacionada à hipertensão arterial sistêmica. Já a esclerose calcificante da média de Monckeberg designa a calcificação, não obstrutiva, da lâmina elástica interna ou da túnica média de artérias musculares. As calcificações vasculares, que incluem lesões ateroscleróticas e a esclerose calcificante da média de Monckeberg, vêm sendo estudadas como um fator de risco para a morbimortalidade cardiovascular.

Abstract Cardiovascular diseases are the main cause of death in contemporary times. Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg's arteriosclerosis are terms that are often used interchangeably, but they refer to different vascular pathologies. The objective of this study is to review the concepts of atherosclerosis, atherosclerosis, arteriosclerosis and Monckeberg medial calcific sclerosis (MMCS). The term arteriosclerosis is more generic, meaning the stiffening and consequent loss of elasticity of the arterial wall, and encompasses the other terms. Atherosclerosis is an inflammatory disease secondary to lesions in the intimal layer and whose main complication is acute and chronic obstruction of the arterial lumen. Arteriolosclerosis refers to thickening of arterioles, particularly in association with systemic arterial hypertension. MMCS refers to non-obstructive calcification in the internal elastic lamina or the tunica media of muscular arteries. Vascular calcifications, which include atherosclerotic lesions and MMCS, have been studied as a risk factor for cardiovascular morbidity and mortality.

Habitual Night Eating Was Positively Associated With Progress of Arterial Stiffness in Chinese Adults.

Background Night eating has been associated with an elevated risk of obesity, dyslipidemia, and cardiovascular disease. However, there is no longitudinal study on whether habitual night eating, regardless of diet quality and energy intake, is associated with arterial stiffness, a major etiological factor in the development of cardiovascular disease. Methods and Results The study included 7771 adult participants without cardiovascular disease, cancer, or diabetes mellitus prior to dietary assessment by a validated food frequency questionnaire in 2014 through 2015. Participants were categorized into 3 groups based on self-reported night-eating habits: never or rarely, some days (1-5 times per week), or most days (6+ times per week). Arterial stiffness was assessed by brachial-ankle pulse wave velocity at baseline and repeatedly during follow-ups. Mean differences and 95% CIs in the yearly change rate of brachial-ankle pulse wave velocity across the 3 groups were calculated, adjusting for age, sex, socioeconomic status, total energy intake, diet quality, sleep quality, and other cardiovascular disease risk factors. At baseline, 6625 (85.2%), 610 (7.8%), and 536 (6.9%) participants reported night eating as never or rarely, some days, or most days, respectively. During a mean 3.19 years, we observed a positive association between night-eating frequency and progression of arterial stiffness (P trend=0.01). The adjusted difference in brachial-ankle pulse wave velocity change rate between the group that ate at night most days and the group that never or rarely ate at night was 14.1 (95% CI, 0.6-27.5) cm/s per year. This association was only significant in women, but not in men (P interaction=0.03). Conclusions In an adult population free of major chronic diseases, habitual night eating was positively associated with the progression of arterial stiffness, a hallmark of arteriosclerosis and biological aging. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-TNRC-11001489.

Cohabiting with Smokers Is an Independent Factor for Worsening Arterial Stiffness Even in Smoking Workers.

Preventing cardiovascular disease (CVD) is an urgent public health challenge. Although brachial-ankle pulse wave velocity (baPWV) can indicate the risk of arterial stiffness and CVD, findings regarding whether baPWV is associated with smoking are inconsistent. This study considered the influence of smoking on arteriosclerosis, specifically focusing on secondhand smoke (SHS), and aimed to construct a strategy for preventing the worsening of arteriosclerosis. We recruited 295 male employees from five companies who had smoking habits such as being smokers, living with smokers, and exposure to SHS outside the home. We measured body composition and hemodynamics, including blood pressure and baPWV, and found that baPWV had significant positive correlations with age, smoking index, alcohol consumption, body-fat percentage, blood pressure, and heart rate, and significant negative correlations with height, fat-free mass, and lower-limb muscle mass. Moreover, baPWV showed a significant adverse effect on participants who had metabolic syndrome (MetS) risk factors such as hypertension, dyslipidemia, and diabetes. Multiple regression analysis showed that baPWV had significant positive relationships with age, height, MetS risk factors, cohabitation with smokers, blood pressure, and heart rate, and a significant negative relationship with lower-limb muscle mass. The same results were obtained when adjusting for current smoking status, smoking index, cohabitation with smokers at birth, and frequency of exposure to SHS outside the home. Exposure to tobacco smoke due to cohabitation with smokers increased baPWV regardless of the person's smoking habits. Thus, to prevent an increase in baPWV in housemates and smokers, it is necessary for smokers to quit smoking.

Epigenetic loci for blood pressure are associated with hypertensive target organ damage in older African Americans from the genetic epidemiology network of Arteriopathy (GENOA) study.

BACKGROUND: Hypertension is a major modifiable risk factor for arteriosclerosis that can lead to target organ damage (TOD) of heart, kidneys, and peripheral arteries. A recent epigenome-wide association study for blood pressure (BP) identified 13 CpG sites, but it is not known whether DNA methylation at these sites is also associated with TOD. METHODS: In 1218 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study, a cohort of hypertensive sibships, we evaluated the associations between methylation at these 13 CpG sites measured in peripheral blood leukocytes and five TOD traits assessed approximately 5 years later. RESULTS: Ten significant associations were found after adjustment for age, sex, blood cell counts, time difference between CpG and TOD measurement, and 10 genetic principal components (FDR q < 0.1): two with estimated glomerular filtration rate (eGFR, cg06690548, cg10601624), six with urinary albumin-to-creatinine ratio (UACR, cg16246545, cg14476101, cg19693031, cg06690548, cg00574958, cg22304262), and two with left ventricular mass indexed to height (LVMI, cg19693031, cg00574958). All associations with eGFR and four associations with UACR remained significant after further adjustment for body mass index (BMI), smoking status, and diabetes. We also found significant interactions between cg06690548 and BMI on UACR, and between 3 CpG sites (cg19693031, cg14476101, and cg06690548) and diabetes on UACR (FDR q < 0.1). Mediation analysis showed that 4.7% to 38.1% of the relationship between two CpG sites (cg19693031 and cg00574958) and two TOD measures (UACR and LVMI) was mediated by blood pressure (Bonferroni-corrected P < 0.05). Mendelian randomization analysis suggests that methylation at two sites (cg16246545 and cg14476101) in PHGDH may causally influence UACR. CONCLUSIONS: In conclusion, we found compelling evidence for associations between arteriosclerotic traits of kidney and heart and previously identified blood pressure-associated DNA methylation sites. This study may lend insight into the role of DNA methylation in pathological mechanisms underlying target organ damage from hypertension.

Association between multi-site atherosclerotic plaques and systemic arteriosclerosis: results from the BEST study (Beijing Vascular Disease Patients Evaluation Study).

BACKGROUND: Arteriosclerosis can be reflected in various aspect of the artery, including atherosclerotic plaque formation or stiffening on the arterial wall. Both arteriosclerosis and atherosclerosis are important and closely associated with cardiovascular disease (CVD). The aim of the study was to evaluate the association between systemic arteriosclerosis and multi-site atherosclerotic plaques. METHODS: The study was designed as an observational cross-sectional study. A total of 1178 participants (mean age 67.4 years; 52.2% male) enrolled into the observational study from 2010 to 2017. Systemic arteriosclerosis was assessed by carotid femoral artery pulse wave velocity (CF-PWV) and multi-site atherosclerotic plaques (MAP, > = 2 of the below sites) were reflected in the carotid or subclavian artery, abdominal aorta and lower extremities arteries using ultrasound equipment. The associations were assessed by multivariable logistic regression. RESULTS: The prevalence of CF-PWV > 12 m/s and MAP were 40.2% and 74.4%. Atherosclerotic plaques in 3 sites were more common in male compared with that in female (48.9% versus 36.9%, p < 0.05). All CVD factors were worse in participants with MAP than that with <=1 site. Participants with CF-PWV > 12 m/s corresponded to a mean 82% probability of MAP with age and sex-adjusted. Patients with peripheral artery disease showed the highest odds ratio (OR) (3.88) for MAP, followed by smoking (2.485), CF-PWV > 12 m/s (2.25), dyslipidemia (1.89), male (1.84), stroke (1.64), hypoglycemic agents (1.56) and age (1.09) (all p < 0.001). CONCLUSIONS: MAP was highly prevalent in this cohort, with male showing a higher prevalence than female. Higher systemic arteriosclerosis was independently associated with MAP, which indicating the supplementary value of arteriosclerosis for the earlier identification and intervention on MAP. TRIAL REGISTRATION: Clinical Trial, URL: http://www.clinicaltrials.gov . Unique identifier: NCT02569268 .

Marked Arterial Functional Changes in Patients With Arterial Vascular Events Across the Early Adult Lifespan.

OBJECTIVE: The age at which arteriosclerosis begins to contribute to events is uncertain. We determined, across the adult lifespan, the extent to which arteriosclerosis-related changes in arterial function occur in those with precipitous arterial events (stroke and critical limb ischemia). Approaches and Results: In 1082 black South Africans (356 with either critical limb ischemia [n=238] or stroke [n=118; 35.4% premature], and 726 age, sex, and ethnicity-matched randomly selected controls), arterial function was evaluated from applanation tonometry and velocity and diameter measurements in the outflow tract. Compared with age- and sex-matched controls, over 10-year increments in age from 20 to 60years, multivariate-adjusted (including steady-state pressures) aortic pulse wave velocity, characteristic impedance (Zc), forward wave pressures (Pf), and early systolic pulse pressure amplification were consistently altered in those with arterial events. Increases in Zc were accounted for by aortic stiffness (no differences in aortic diameter) and Pf by changes in Zc and not aortic flow or wave re-reflection. Multivariate-adjusted pulse wave velocity (7.48±0.30 versus 5.82±0.15 m/s, P<0.0001), Zc (P<0.0005), and Pf (P<0.0001) were higher and early systolic pulse pressure amplification lower (P<0.0001) in those with precipitous events than in controls. In comparison to age- and sex-matched controls, independent of risk factors, pulse wave velocity, and Zc (P<0.005 and <0.05) were more closely associated with premature events than events in older persons and Pf and early systolic pulse pressure amplification were at least as closely associated with premature events as events in older persons. CONCLUSIONS: Arteriosclerosis-related changes in arterial function are consistently associated with arterial events beyond risk factors from as early as 20 years of age.

Schimke immuno-osseous dysplasia, two new cases with peculiar EEG pattern.

INTRODUCTION: Schimke Immuno-Osseous Dysplasia (SIOD) is an autosomal recessive multisystem disorder caused by pathogenic variants in the gene SMARCAL1. The clinical picture is characterized by spondyloepiphyseal dysplasia resulting in growth failure, nephropathy and T-cell deficiency. Neurologic manifestations include microcephaly, cognitive impairment, migraine-like headaches and cerebrovascular manifestations such as cerebral atherosclerotic vascular disease and reversible cerebral vasoconstriction. The role of SMARCAL1 deficiency in non-vascular neurological complications is still under debate. Epilepsy has been reported in a few patients, even in the absence of brain abnormalities. Data regarding electroencephalographic (EEG) patterns in SIOD are scarce METHODS: We describe the clinical, neuroradiological and EEG findings in two unrelated patients with SIOD showing a peculiar pseudo-periodic EEG pattern apparently not related to the cerebrovascular complications, since it was recognized both before and after cerebrovascular events CONCLUSION: Our observations support the hypothesis that SMARCAL1plays an important role in neurodevelopment and brain function and expand the spectrum of neurological abnormalities related to SIOD.

Association between ossification of the longitudinal ligament of the cervical spine and arteriosclerosis in the carotid artery.

Although several risk factors have been reported for cervical ossification of the longitudinal ligament (OPLL), most evaluations made in the past were based on plain X-ray, not on computed tomography (CT) scan. In this study, we aimed to clarify novel risk factors for cervical OPLL in asymptomatic subjects undergoing CT scan as their routine medical checkups. A total of 1789 Japanese asymptomatic subjects who underwent CT scan for the whole body as their routine medical checkups were retrospectively reviewed. The medical checkup also included laboratory examinations, bone mineral status, and ultrasound of the carotid artery. As a result, cervical OPLL was seen in 120 subjects (6.7%). As we compared the demographic and clinical data between subjects with and without OPLL, OPLL group showed older age, higher proportion of male sex, higher BMI, higher incidence of hypertension, higher levels of blood HbA1c and triglyceride, and higher incidence of plaques in the carotid artery. A multivariate logistic regression analysis revealed that age (Odds ratio (OR):1.03), male sex (OR: 1.91), and the presence of plaque in the carotid artery (OR: 1.71) were risk factors for OPLL. To the best of our knowledge, this is the first report to reveal an association between OPLL and arteriosclerotic lesions.

Surgical versus endovascular revascularization of subclavian artery arteriosclerotic disease.

BACKGROUND: Endovascular treatment offers an alternative, less invasive approach to open repair for subclavian artery atherosclerotic disease (SAAD). However, only few studies compared the outcomes of both strategies in the long run. This study reports on the performance of endovascular and surgical revascularization for SAAD. METHODS: A retrospective review was conducted on patients treated for SAAD at two institutions between January 1998 and December 2015. Primary outcome of this study was the composite endpoint of reintervention-free survival (RFS) defined as time to reintervention and/or death from any cause. Secondary endpoints included primary patency (PPR) and secondary patency (SPR) rates as well as overall survival and time to reintervention. RESULTS: Surgical treatment was the preferred treatment option in 27 (25%) patients, while 83 (75%) patients underwent primary stent therapy. The median follow-up was 87 months (interquartile range [IQR]: 38 to 151) in the surgical group and 27 (IQR: 12 to 59) in the endovascular (P=0.0001). Severe arterial wall calcification was more commonly observed in the surgical arm (P<0.0001), while mild and moderate calcification in the endovascular (P=0.0004 and P=0.014). Vessel occlusion was more frequent among patients treated surgically (100% vs. 34%, P<0.0001). At 98 months RFS was significantly higher after surgical treatment (95% vs. 54%, HR: 8.4, 95% CI: 3.9 to 18.1, P=0.0002). Although overall survival did not differ significantly between the two groups (HR: 4.28, 95% CI: 0.86 to 21.22, P=0.093), open repair was associated with reduced reintervention rate (HR: 12.04, 95% CI: 4.98 to 29.12, P=0.001). The PPR at 98 months following surgical and endovascular therapy amounted to 96% and 65% (HR: 12.87, 95% CI: 5.44 to 30.44, P=0.0008) respectively. No significant difference was observed regarding the SPR between the two groups (100% vs. 95%, P=0.090). CONCLUSIONS: Surgical treatment was associated in this cohort with increased patency and a significant reduction of reinterventions compared to the endovascular approach.

Carotid artery blood velocity decreases in patients with coronary slow flow: A manifestation of systemic arteriosclerosis.

OBJECTIVES: Coronary slow flow phenomenon (CSFP) could be a manifestation of systemic arteriosclerosis, as coronary and carotid arteries have similar intimal thickening. However, as an initial cause of arteriosclerosis, hemodynamic changes in carotid arteries have rarely been studied. METHODS: Twenty patients with angiography-proven CSFP and 39 patients with normal coronary flow (NCF) were enrolled. TIMI frame counts (CTFC) were investigated. Carotid intima-media thickness (CIMT), peak systolic velocity (PSV), and end-diastolic velocity (EDV) were measured by ultrasonography, and shear rate (SR) and resistance index (RI) were calculated. RESULTS: The results showed that PSV, EDV, SR, and RI were significantly lower in patients with CSFP (p＜0.01), but CIMT was significantly increased (P ï¼œ 0.01). PSV, EDV, SR, and RI were negatively correlated with CTFC, while CIMT was positively correlated with CTFC. Logistic regression analysis revealed that PSV (OR = 0.95, P < 0.01) could be an independent protective factor against CSFP, but CIMT (OR = 1.10, P ï¼œ 0.05) and male gender (OR = 9.89, P ï¼œ 0.01) could be risk factors for CSFP. CONCLUSIONS: The slow flow phenomenon was observed in both coronary and carotid arteries, which could be a characteristic manifestation of systemic arteriosclerosis in CSFP; the lower wall shear stress may be the underlying mechanism. Carotid ultrasound could be applied in the noninvasive diagnosis of CSFP in the future.

Association between acute aortic dissection and the distribution of aortic calcification.

OBJECTIVE: Aortic calcification (AC) is associated with increased risks of cardiovascular events and mortality. Numerous studies have explored the association between calcification and abdominal artery aneurysm. However, evidence regarding the association between AC and acute aortic dissection (AAD) is limited. We aimed to evaluate the association between AC-related variables and the development of intimal tear (IT) in patients with AAD. METHODS: We conducted a retrospective observational study involving 64 patients with type A AAD and 32 patients with type B AAD from February, 2011 to January, 2017 at a tertiary referral medical center in Taiwan. We used the default analysis module "calcification score analysis" to calculate all the calcification variables, including AC scores and volume. RESULTS: We identified an association between AC and AAD. Patients with AAD had a greater AC volume in the aortic arch and greater AC scores for both the ascending aorta and the aortic arch than did patients without AAD. However, hypertension and coronary artery disease, rather than AC remained to be the independent risk factor for AAD in multivariate analysis. Patients with type A AAD had greater mean and cumulative AC volumes in the aortic arch, greater cumulative AC volumes in the whole aorta and higher cumulative AC scores in the aortic arch than did patients with type B AAD. ACs were superimposed on ITs in nearly half of the patients with AAD. In patients with type A AAD, AC was more commonly located distal to the IT and farther from the IT. CONCLUSIONS: We identified the associations between AC-related variables and the location of IT in patients with AAD. However, AC was not an independent risk factor for AAD. The distribution of AC was different between patients with type A and type B AAD.

Association Between Body Mass Index (BMI) and Brachial-Ankle Pulse Wave Velocity (baPWV) in Males with Hypertension: A Community-Based Cross-Section Study in North China.

BACKGROUND The aim of this study was to investigate the association between body mass index (BMI) and brachial-ankle pulse wave velocity (baPWV) in hypertensive males. MATERIAL AND METHODS Altogether, 14 866 male hypertensive participants were included in the analysis. Participants were divided into 3 groups: low BMI group (BMI <24 kg/m²), moderate BMI group (24 kg/m² ≤BMI <28 kg/m²), and high BMI group (BMI ≥28 kg/m²). According to baPWV values, arteriosclerosis (AS) was set as 3 degrees: mild AS (baPWV ≥1400 cm/s), moderate AS (baPWV ≥1700 cm/s) and severe AS (baPWV ≥2000 cm/s). Multivariate logistic regression analysis was used to explore the effect of different BMI groups on different degrees of AS. The multivariate linear regression analysis was used to explore the relationship between BMI and baPWV. RESULTS Among low BMI, moderate BMI, and high BMI groups, the average baPWV values were 1824±401 cm/s, 1758±363 cm/s, and 1686±341 cm/s, respectively. Prevalence in the mild, moderate and high BMI groups were 91.0%, 87.8%, 81.5%, respectively for mild AS; 55.3%, 48.8%, and 40.0% respectively for moderate AS; and 25.9%, 20.2%, and 14.9% respectively for severe AS. Compared to the low BMI group, multivariate logistic regression analysis showed that odds ratio (OR) and 95% confidence intervals (95%CI) in the moderate BMI group and the high BMI were 0.71 (95%Cl, 0.62-0.80), 0.43 (95%Cl, 0.38-0.50) for mild AS; and similar trends were shown for moderate AS and severe AS. Based on age-stratification, a negative relationship remained for 35-55 years old participants for different degrees of AS among the moderate BMI group and the high BMI group. A negative relationship was detected between BMI and baPWV in total and different age-stages. CONCLUSIONS Among male hypertension participants in this study, there was a negative relationship between BMI and baPWV. High BMI was found to be a protective factor for AS especially in the age range of 35-55 years.