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1.
Metabolism ; 116: 154706, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33421505

RESUMO

BACKGROUND: Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular risk factors that correlate with each other. We hypothesized that other cardiovascular risk factors could affect their relationship. METHODS: We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years in 5975 Multi-Ethnic Study of Atherosclerosis (MESA) participants, free of apparent cardiovascular disease at baseline. RESULTS: Elevated Lp(a) was associated with larger absolute increase in CAC volume (3.21 and 4.45 mm3/year higher for Lp(a) ≥30 versus <30 mg/dL, and Lp(a) ≥50 versus <50 mg/dL, respectively), but not relative change in CAC volume. No association was found with change in CAC density when assessing continuous ln-transformed Lp(a). The association between elevated Lp(a) (≥30 mg/dL) and absolute change in CAC volume was greater in participants with higher circulating levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor alpha receptor 1 and fibrinogen (15.33, 11.81 and 7.02 mm3/year in quartile 4, compared to -3.44, -0.59 and 1.91 mm3/year in quartile 1, respectively). No significant interaction was found for other study variables. Similar interactions were seen when assessing Lp(a) levels ≥50 mg/dL. CONCLUSIONS: Elevated Lp(a) was associated with an absolute increase in CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. These results suggest Lp(a) as a potential biomarker for CAC volume progression.

2.
JAMA Netw Open ; 4(1): e2030435, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33399855

RESUMO

Importance: The incidence of and mortality from coronary heart disease (CHD) are substantially higher among African American individuals compared with non-Hispanic White individuals, even after adjusting for traditional factors associated with CHD. The unexplained excess risk might be due to genetic factors related to African ancestry that are associated with a higher risk of CHD, such as the heterozygous state for the sickle cell variant or sickle cell trait (SCT). Objective: To evaluate whether there is an association between SCT and the incidence of myocardial infarction (MI) or composite CHD outcomes in African American individuals. Design, Setting, and Participants: This cohort study included 5 large, prospective, population-based cohorts of African American individuals in the Women's Health Initiative (WHI) study, the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, the Multi-Ethnic Study of Atherosclerosis (MESA), the Jackson Heart Study (JHS), and the Atherosclerosis Risk in Communities (ARIC) study. The follow-up periods included in this study were 1993 and 1998 to 2014 for the WHI study, 2003 to 2014 for the REGARDS study, 2002 to 2016 for the MESA, 2002 to 2015 for the JHS, and 1987 to 2016 for the ARIC study. Data analysis began in October 2013 and was completed in October 2020. Exposures: Sickle cell trait status was evaluated by either direct genotyping or high-quality imputation of rs334 (the sickle cell variant). Participants with sickle cell disease and those with a history of CHD were excluded from the analyses. Main Outcomes and Measures: Incident MI, defined as adjudicated nonfatal or fatal MI, and incident CHD, defined as adjudicated nonfatal MI, fatal MI, coronary revascularization procedures, or death due to CHD. Cox proportional hazards regression models were used to estimate the hazard ratio for incident MI or CHD comparing SCT carriers with noncarriers. Models were adjusted for age, sex (except for the WHI study), study site or region of residence, hypertension status or systolic blood pressure, type 1 or 2 diabetes, serum high-density lipoprotein level, total cholesterol level, and global ancestry (estimated from principal components analysis). Results: A total of 23 197 African American men (29.8%) and women (70.2%) were included in the combined sample, of whom 1781 had SCT (7.7% prevalence). Mean (SD) ages at baseline were 61.2 (6.9) years in the WHI study (n = 5904), 64.0 (9.3) years in the REGARDS study (n = 10 714), 62.0 (10.0) years in the MESA (n = 1556), 50.3 (12.0) years in the JHS (n = 2175), and 53.2 (5.8) years in the ARIC study (n = 2848). There were no significant differences in the distribution of traditional factors associated with cardiovascular disease by SCT status within cohorts. A combined total of 1034 participants (76 with SCT) had incident MI, and 1714 (137 with SCT) had the composite CHD outcome. The meta-analyzed crude incidence rate of MI did not differ by SCT status and was 3.8 per 1000 person-years (95% CI, 3.3-4.5 per 1000 person-years) among those with SCT and 3.6 per 1000 person-years (95% CI, 2.7-5.1 per 1000 person-years) among those without SCT. For the composite CHD outcome, these rates were 7.3 per 1000 person-years (95% CI, 5.5-9.7 per 1000 person-years) among those with SCT and 6.0 per 1000 person-years (95% CI, 4.9-7.4 per 1000 person-years) among those without SCT. Meta-analysis of the 5 study results showed that SCT status was not significantly associated with MI (hazard ratio, 1.03; 95% CI, 0.81-1.32) or the composite CHD outcome (hazard ratio, 1.16; 95% CI, 0.92-1.47). Conclusions and Relevance: In this cohort study, there was not an association between SCT and increased risk of MI or CHD in African American individuals. These disorders may not be associated with sickle cell trait-related sudden death in this population.

3.
J Occup Environ Med ; Publish Ahead of Print2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33405497

RESUMO

INTRODUCTION: Research on the effect of occupation on cardiovascular health (CVH) among older women is limited. METHODS: Each of the 7 American Heart Association's CVH metrics was scored as ideal (1) or non-ideal (0) and summed. Multivariable logistic regression was used to estimate the odds of poor overall CVH (CVH score of 0-2) comparing women employed in each of the top 20 occupational categories to those not employed in that category, adjusting for age, marital status, and race/ethnicity. RESULTS: 1) Bookkeeping, accounting, and auditing clerks; 2) first-line supervisors of sales workers; 3) first-line supervisors of office and administrative support workers; and 4) nursing, psychiatric, and home health aides were more likely to have poor overall CVH compared to women who did not work in these occupations. CONCLUSIONS: Several commonly held occupations among women were associated with poor CVH.

4.
J Psychiatr Res ; 133: 119-124, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33338734

RESUMO

Previous studies suggested a potential relationship between plasma lipoprotein (a) [Lp(a)] and elevated depressive symptoms. We aimed to investigate any such relationship in the Multi-Ethnic Study of Atherosclerosis participants who were free of cardiovascular events. Analysis included 4938 participants without elevated depressive symptoms and with Lp(a) levels measured at baseline. Participants were examined at four clinic visits over a 10-year period. Elevated depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D) and were defined as a CES-D score ≥16 or use of anti-depressants. Lp(a) level was measured with a latex-enhanced turbidimetric immunoassay. After adjusting for demographics, socioeconomic factors and other confounding factors in Cox regression analyses, a higher ln-transformed Lp(a) level was associated with new elevated depressive symptoms since baseline (hazard ratio [95% CI] = 1.09 [1.02-1.16] per SD increment in ln-transformed level, P = 0.01). However, no association was found when elevated Lp(a) levels were assessed using clinical cut-off point (≥30 or 50 mg/dL), nor in sensitivity analyses using alternative definitions of elevated depressive symptoms. No significant interaction with race/ethnicity was found for all the above analyses. Also, no significant association was found between baseline Lp(a) levels and absolute or relative changes in CES-D score between baseline and last follow-up visits. Our study suggests a potential association between Lp(a) level and new elevated depressive symptoms, but such association was not robust in the sensitivity analyses. Future studies are warranted to investigate the role of Lp(a) in depressive symptoms in other cohorts.

5.
Prim Care Diabetes ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33309035

RESUMO

AIMS: To investigate associations of health insurance with measures of glucose metabolism, and whether associations vary by diabetes status or insurance type. METHODS: Cross-sectional analysis of baseline data from the Multi-Ethnic Study of Atherosclerosis. Cohort a priori stratified by age <65 (N = 3,665) and ≥65 years (N = 2,924). Multivariable linear and logistic regression assessed associations between insurance and fasting glucose, HOMA-IR, and prevalent diabetes, controlling for relevant confounders, including age, sex, race/ethnicity, income, and education. RESULTS: In participants <65, compared to uninsured, having any insurance was associated with lower fasting glucose in participants with diabetes (Mean Difference = -20.4 mg/dL, P = 0.01), but not in participants without diabetes. Compared to Private insurance, uninsured participants had higher fasting glucose (Mean Difference = 3.8 mg/dL, P = 0.03), while participants with Medicaid had higher HOMA-IR (Mean Difference = 3.5 mg/dL, P < 0.01). In participants ≥65, compared to Private insurance, uninsured participants (Mean Difference = 7.5 mg/dL, P = 0.02), and participants with Medicaid only (Mean Difference = 19.9 mg/dL, P < 0.01) or Medicare + Medicaid (Mean Difference = 5.2 mg/dL, P = 0.03) had higher fasting glucose. CONCLUSIONS: In this large multiethnic cohort, having any insurance was associated with significantly lower fasting glucose for individuals with diabetes. Levels of fasting glucose and insulin resistance varied across different insurance types.

6.
Br J Nutr ; : 1-10, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33308330

RESUMO

South Asians, who are at a disproportionately greater risk of atherosclerotic CVD (ASCVD), represent a rapidly growing population in the USA. The relationship between dairy products, a major component of South Asian diets, and body composition - an established risk factor for ASCVD, is unclear. The aim of the present study was to examine associations between dairy intake and multiple measures of body composition (BMI, waist and hip circumference, waist:hip ratio, abdominal lean mass, subcutaneous, visceral, and intermuscular fat areas) among South Asian adults in the USA. A baseline analysis was conducted using existing data from the Mediators of Atherosclerosis in South Asians Living in America cohort. In women, the highest (>1·9 servings/d) v. lowest (<1 serving/d) tertile of dairy intake was associated with 53 % lower odds of a waist circumference >80 cm (95 % CI 0·25, 0·89, Pfor trend<0·05). No associations were observed between dairy intake and measures of body composition. However, >3 servings of low-fat yogurt/week was associated with a 9·9 cm2 lower visceral fat area (95 % CI -19·07, -0·72, P<0·05) and 2·3 cm2 lower intermuscular fat area (95 % CI -3·76, -0·79, P<0·05) as compared with those with three servings/week. Milk and cheese were not associated with body composition measures. These analyses suggest that higher consumption of low-fat yogurt is associated with lower visceral and intermuscular fat in the whole sample, and women with higher dairy intake have lower waist circumference. Our study supports dietary incorporation of dairy products, and recognises the utility of multidimensional measures of central adiposity.

7.
Am J Clin Nutr ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33330926

RESUMO

BACKGROUND: The potential cardiovascular impact of dietary cholesterol intake has been actively debated for decades. OBJECTIVES: We aimed to evaluate associations of dietary cholesterol and egg intakes with incident cardiovascular disease (CVD) and all-cause and cause-specific mortality. METHODS: We included 96,831 US postmenopausal women aged 50-79 y without known CVD or cancer during baseline enrollment (1993-1998) of the Women's Health Initiative. Dietary information was collected using a validated FFQ. Incident CVD [i.e., ischemic heart disease (IHD) and stroke] and all-cause and cause-specific mortality were ascertained and adjudicated through February 2018. RESULTS: A total of 9808 incident CVD cases and 19,508 all-cause deaths occurred during a median follow-up of 17.8 y and 18.9 y, respectively. After multivariable adjustment for traditional risk factors and key dietary nutrients including dietary saturated fat, there were modest associations of dietary cholesterol intake with incident CVD (HRQ5versusQ1: 1.12; 95% CI: 1.03, 1.21; P-trend < 0.001) and all-cause mortality (HRQ5versusQ1: 1.09; 95% CI: 1.02, 1.15; P-trend < 0.001). Significant positive associations were also observed between dietary cholesterol and incident IHD (P-trend = 0.007), incident ischemic stroke (P-trend = 0.002), and CVD mortality (P-trend = 0.002), whereas there was an inverse association for incident hemorrhagic stroke (P-trend = 0.037) and no association for mortality from cancer, Alzheimer disease/dementia, respiratory diseases, or other causes (P-trend > 0.05). Higher egg consumption was also associated with modestly higher risk of incident CVD (P-trend = 0.004) and all-cause mortality (P-trend < 0.001), with HRs of 1.14 (95% CI: 1.04, 1.25) and 1.14 (95% CI: 1.07, 1.22), respectively, when comparing ≥1 egg/d with <1 egg/wk. CONCLUSIONS: Both higher dietary cholesterol intake and higher egg consumption appeared to be associated with modestly elevated risk of incident CVD and all-cause mortality in US postmenopausal women.

8.
J Hypertens ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33239550

RESUMO

OBJECTIVES: The radial artery pulse waveform is a continuous measure of pressure throughout the cardiac cycle, and thus can provide more information than just systolic and diastolic blood pressures. New indices based on a Windkessel model of the waveform, PTC1 and PTC2, are related to arterial compliance and add information for prediction of incident cardiovascular disease (coronary heart disease, stroke, myocardial infarction) but their association with heart failure is unknown. METHODS: Among 6229 adults (mean age 62 years) from four race/ethnic groups who were initially free of clinical cardiovascular disease and heart failure in 2000-2002, we evaluated the associations of baseline PTC1 and PTC2 with incident heart failure. RESULTS: Mean ±â€Šstandard deviation PTC1 and PTC2 were 394 ±â€Š334 and 94 ±â€Š46 ms, respectively. During a median of 15.7 years follow-up, there were 357 heart failure events (148 with reduced, 150 with preserved, and 59 with unknown ejection fraction). After adjustment for traditional risk factors, the hazard ratio for heart failure per 1 standard deviation higher PTC2 was 0.73 (95% confidence interval: 0.63--0.85). Higher PTC2 was also significantly associated with lower risk of heart failure with reduced ejection fraction (hazard ratio = 0.67; 95% confidence interval: 0.56--0.80). There was no evidence of a significant association between PTC2 and heart failure with preserved ejection fraction or between PTC1 and heart failure. CONCLUSION: The PTC2 measure of the radial artery pulse waveform may represent a novel phenotype related to heart failure, especially heart failure with reduced ejection fraction.

9.
Circulation ; : CIR0000000000000912, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33251828

RESUMO

Cardiovascular disease (CVD) is the leading cause of death in women, who have a notable increase in the risk for this disease after menopause and typically develop coronary heart disease several years later than men. This observation led to the hypothesis that the menopause transition (MT) contributes to the increase in coronary heart disease risk. Over the past 20 years, longitudinal studies of women traversing menopause have contributed significantly to our understanding of the relationship between the MT and CVD risk. By following women over this period, researchers have been able to disentangle chronological and ovarian aging with respect to CVD risk. These studies have documented distinct patterns of sex hormone changes, as well as adverse alterations in body composition, lipids and lipoproteins, and measures of vascular health over the MT, which can increase a woman's risk of developing CVD postmenopausally. The reported findings underline the significance of the MT as a time of accelerating CVD risk, thereby emphasizing the importance of monitoring women's health during midlife, a critical window for implementing early intervention strategies to reduce CVD risk. Notably, the 2011 American Heart Association guidelines for CVD prevention in women (the latest sex-specific guidelines to date) did not include information now available about the contribution of the MT to increased CVD in women. Therefore, there is a crucial need to discuss the contemporary literature on menopause and CVD risk with the intent of increasing awareness of the significant adverse cardiometabolic health-related changes accompanying midlife and the MT. This scientific statement provides an up-to-date synthesis of the existing data on the MT and how it relates to CVD.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33231259

RESUMO

CONTEXT: Glycogen storage diseases are rare. Increased glycogen in the liver results in increased attenuation. OBJECTIVE: Investigate the association and function of a noncoding region associated with liver attenuation but not histologic nonalcoholic fatty liver disease. DESIGN: Genetics of Obesity-associated Liver Disease Consortium. SETTING: Population-based Main Outcome: Computed tomography measured liver attenuation. RESULTS: Carriers of rs4841132-A (frequency 2-19%) do not show increased hepatic steatosis; they have increased liver attenuation indicative of increased glycogen deposition. rs4841132 falls in a noncoding RNA LOC157273 ~190kb upstream of PPP1R3B. We demonstrate that rs4841132-A increases PPP1R3B through a cis genetic effect. Using CRISPR/Cas9 we engineered a 105bp deletion including rs4841132-A in human hepatocarcinoma cells which increases PPP1R3B, decreases LOC157273 and increases glycogen perfectly mirroring the human disease. Overexpression of PPP1R3B or knockdown of LOC157273 increased glycogen but did not result in decreased LOC157273 or increased PPP1R3B, respectively, suggesting that the effects may not all occur via affecting RNA levels. Based on EHR data, rs4841132-A associates with all components of the metabolic syndrome (MetS). However, rs4841132-A associated with decreased low-density lipoprotein (LDL) cholesterol and risk for myocardial infarction (MI). A metabolic signature for rs4841132-A includes increased glycine, lactate, triglycerides and decreased acetoacetate and beta-hydroxybutyrate. CONCLUSIONS: These results show that rs4841132-A promotes a hepatic glycogen storage disease by increasing PPP1R3B and decreasing LOC157273. rs4841132-A promotes glycogen accumulation and development of MetS but lowers LDL cholesterol and risk for MI. These results suggest that elevated hepatic glycogen is one cause of MetS that does not invariably promote MI.

11.
Ann Surg ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33156064

RESUMO

OBJECTIVE: To determine if premature menopause and early menarche are associated with increased risk of AAA, and to explore potential effect modification by smoking history. SUMMARY OF BACKGROUND DATA: Despite worse outcomes for women with AAA, no studies have prospectively examined sex-specific risk factors, such as premature menopause and early menarche, with risk of AAA in a large, ethnically diverse cohort of women. METHODS: This was a post-hoc analysis of Women's Health Initiative participants who were beneficiaries of Medicare Parts A&B fee-for-service. AAA cases and interventions were identified from claims data. Follow-up period included Medicare coverage until death, end of follow-up or end of coverage inclusive of 2017. RESULTS: Of 101,119 participants included in the analysis, the mean age was 63 years and median follow-up was 11.3 years. Just under 10,000 (9.4%) women experienced premature menopause and 22,240 (22%) experienced early menarche. Women with premature menopause were more likely to be overweight, Black, have ≥20 pack years of smoking, history of cardiovascular disease, hypertension, and early menarche. During 1,091,840 person-years of follow-up, 1125 women were diagnosed with AAA, 134 had premature menopause (11.9%), 93 underwent surgical intervention and 45 (48%) required intervention for ruptured AAA. Premature menopause was associated with increased risk of AAA [hazard ratio 1.37 (1.14, 1.66)], but the association was no longer significant after multivariable adjustment for demographics and cardiovascular disease risk factors. Amongst women with ≥20 pack year smoking history (n = 19,286), 2148 (11.1%) had premature menopause, which was associated with greater risk of AAA in all models [hazard ratio 1.63 (1.24, 2.23)]. Early menarche was not associated with increased risk of AAA. CONCLUSIONS: This study finds that premature menopause may be an important risk factor for AAA in women with significant smoking history. There was no significant association between premature menopause and risk of AAA amongst women who have never smoked. These results suggest an opportunity to develop strategies for better screening, risk reduction and stratification, and outcome improvement in the comprehensive vascular care of women.

12.
Chemistry ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073884

RESUMO

The synthesis and characterisation of new bis(bipyridine)ruthenium(II) ferrocenyl ß-diketonate complexes, [(bpy)2Ru(Fc-acac)][PF6] (bpy = 2,2'-bipyridine; Fc-acac = functionalized ferrocenyl ß-diketonate ligand) are reported. Alongside clinical platinum drugs, these bimetallic ruthenium-iron complexes have been screened for their cytotoxicity against MIA PaCa-2 (human pancreatic carcinoma), HCT116 p53+/+ (human colon carcinoma, p53-wild type) and ARPE-19 (human retinal pigment epithelial) cell lines. With the exception of one complex, the library exhibit nanomolar potency against cancerous cell lines, and their relative potencies are up to 40x, 400x and 72x more cytotoxic than cisplatin, carboplatin and oxaliplatin, respectively. Under hypoxic conditions, the complexes remain cytotoxic (sub-micromolar range), highlighting their potential in targeting hypoxic tumour regions. The Comet assay was used to determine their ability to damage DNA, and results show dose dependent damage which correlates well with the cytotoxicity results. Their potential to treat bacterial and fungal strains has been determined, and highlight complexes have selective growth inhibition of up to 87-100% against Staphylococcus aureus and Candida albicans.

13.
J Am Coll Cardiol ; 76(12): 1455-1465, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32943164

RESUMO

BACKGROUND: Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear. OBJECTIVES: The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF. METHODS: The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio. RESULTS: Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p < 0.001), and the combined clinical model had good discrimination in men (C-statistic = 0.80) and in women (C-statistic = 0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic = 0.006; likelihood ratio chi-square = 146; p < 0.001), and after adding cardiac troponins in women (ΔC-statistic = 0.003; likelihood ratio chi-square = 73; p < 0.001). CONCLUSIONS: CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in a clinical HF risk prediction model is limited in both sexes.

14.
Diabetes ; 69(12): 2806-2818, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32917775

RESUMO

Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.

15.
JAMA Cardiol ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32936228

RESUMO

Importance: Atherosclerotic cardiovascular disease (ASCVD) may have unique risk factors in women. Most women have a history of pregnancy; common adverse pregnancy outcomes (APOs) appear to be associated with ASCVD, but prior studies have limitations. Objective: To assess whether APOs are associated with increased ASCVD risk independently of traditional risk factors. Design, Setting, and Participants: The APO history among participants in the Women's Health Initiative, a large multiethnic cohort of postmenopausal women, was assessed. The associations of 5 self-reported APOs (gestational diabetes, hypertensive disorders of pregnancy, low birth weight [ie, birth weight less than 2.49 kg], high birth weight [ie, birth weight greater than 4.08 kg], and preterm delivery by 3 weeks or more) with ASCVD were analyzed, adjusting for traditional ASCVD risk factors. Data were collected and analyzed in 2017. Exposures: APOs (gestational diabetes, hypertensive disorders of pregnancy, low birth weight, high birth weight, and preterm delivery). Main Outcomes and Measures: Adjudicated ASCVD. Results: A total of 48 113 Women's Health Initiative participants responded to the survey; the median (interquartile range) age at time of enrollment was 60.0 (55.0-64.0) years. A total of 13 482 participants (28.8%) reported 1 or more APOs. Atherosclerotic cardiovascular disease was more frequent in women who reported an APO compared with those without APOs (1028 of 13 482 [7.6%] vs 1758 of 30 522 [5.8%]). Each APO, analyzed separately, was significantly associated with ASCVD, and gestational diabetes, hypertensive disorders of pregnancy, low birth weight, and preterm delivery remained significant after adjustment for traditional ASCVD risk factors. When all APOs were analyzed together, hypertensive disorders of pregnancy (odds ratio, 1.27; 95% CI, 1.15-1.40) and low birth weight (odds ratio, 1.12; 95% CI, 1.00-1.26) remained independently associated with ASCVD. All findings were materially unchanged by additional adjustment for parity, body mass index, and socioeconomic factors. Conclusions and Relevance: In this large multiethnic cohort of women, hypertensive disorders of pregnancy and low birth weight were independently associated with ASCVD after adjustment for risk factors and other APOs.

16.
J Vasc Surg ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32882349

RESUMO

OBJECTIVE: Few studies have prospectively examined the associations of lipoprotein(a) [Lp(a)] levels with the risk of abdominal aortic aneurysm (AAA), especially in women. Accounting for commonly recognized risk factors, we investigated the baseline Lp(a) levels and the risk of AAA among postmenopausal women participating in the ongoing national Women's Health Initiative. METHODS: Women's Health Initiative participants with baseline Lp(a) levels available who were beneficiaries of Medicare parts A and B fee-for-service at study enrollment or who had aged into Medicare at any point were included. Participants with missing covariate data or known AAA at baseline were excluded. Thoracic aneurysms were excluded owing to the different pathophysiology. The AAA cases and interventions were identified using the International Classification of Diseases, 9th and 10th revision, codes and Current Procedural Terminology codes from claims data. Hazard ratios were computed using Cox proportional hazard models according to the quintiles of Lp(a). RESULTS: The mean age of the 6615 participants included in the analysis was 65.3 years. Of the 6615 participants, 66.6% were non-Hispanic white, 18.9% were black, 7% were Hispanic and 4.7% were Asian/Pacific Islander. Compared with the participants in the lowest Lp(a) quintile, those in higher quintiles were more likely to be overweight, black, and former or current smokers, to have hypertension, hyperlipidemia, and a history of cardiovascular disease, and to use menopausal hormone therapy and statins. During 65,476 person-years of follow-up, with a median of 10.4 years, 415 women had been diagnosed with an AAA and 36 had required intervention. More than one half had required intervention for a ruptured AAA. We failed to find a statistically significant association between Lp(a) levels and incident AAA. Additional sensitivity analyses stratified by race, with exclusion of statin users and alternative categorizations of Lp(a) using log-transformed levels, tertiles, and a cutoff of >50 mg/dL, were conducted, which did not reveal any significant associations. CONCLUSIONS: We found no statistically significant association between Lp(a) levels and the risk of AAA in a large and well-phenotyped sample of postmenopausal women. Women with high Lp(a) levels were more likely to be overweight, black, and former or current smokers, and to have hypertension, hyperlipidemia, and a history of cardiovascular disease, or to use hormone therapy and statins compared with those with lower Lp(a) levels. These findings differ from previous prospective, case-control, and meta-analysis studies that had supported a significant relationship between higher Lp(a) levels and an increased risk of AAA. Differences in the association could have resulted from study limitations or sex differences.

17.
Kidney Med ; 2(1): 68-75, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32734227

RESUMO

Rationale & Objective: A low ankle-brachial index (ABI) is used to diagnose peripheral artery disease (PAD) but may be normal or elevated in patients with medial arterial calcification and stiff vessels, as is common in chronic kidney disease (CKD). The toe-brachial index (TBI) has been recommended because it is not influenced by medial arterial calcification, but alone the TBI does not capture risk associated with medial arterial calcification. We hypothesized that the difference between ABI and TBI (ABI - TBI) would capture both PAD and medial arterial calcification and thus better identify mortality risk from PAD, particularly in those with CKD. Study Design: Prospective cohort study. Setting & Participants: 471 patients with clinical suspicion for PAD referred for vascular testing. Exposures: ABI, TBI, and ABI - TBI. Outcome: All-cause mortality. Analytical Approach: Cox proportional hazards models evaluating the association of ABI - TBI with mortality over 7 years. Results: Mean age was 68 years, 89% were men, 35% had diabetes, 64% had CKD, and mean estimated glomerular filtration rate was 55 mL/min/1.73 m2. Median ABI was 0.96 (interquartile range [IQR], 0.73-1.08), median TBI was 0.62 (IQR, 0.46-0.81), and median ABI - TBI was 0.23 (IQR, 0.14-0.39). Higher ABI - TBI values were associated with increased risk in mortality only among participants with ABI values ≥ 0.9 (P = 0.03). Among participants with CKD and ABI values ≥ 0.9, participants with ABI - TBI values higher than the median had greater (HR, 1.79; 95% CI, 1.18-2.72) risk for mortality (P = 0.005). This was attenuated after age adjustment (HR, 1.41; 95% CI, 0.91-2.20) but did not change after further adjustment for confounders. Limitations: Mainly male cohort derived from a vascular laboratory; lack of limb outcomes and data for albuminuria. Conclusions: A high ABI - TBI value may be associated with higher risk for mortality in persons with CKD and a normal ABI. Age affects this association, and further studies evaluating ABI - TBI in larger populations are required.

18.
J Am Heart Assoc ; 9(16): e015451, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32752978

RESUMO

Background Underuse of cardiovascular medications for secondary prevention among individuals with peripheral artery disease (PAD) has been reported. Little is known about PAD treatment status in the Hispanic/Latino population in the United States, who may have limited access to health care and who have worse clinical outcomes than non-Hispanic individuals. Methods and Results We studied the use of cardiovascular therapies in 1244 Hispanic/Latino individuals recruited from 4 sites in the United States, including 826 individuals who reported diagnosis of PAD by physician and 418 individuals with coronary artery disease alone, in the Hispanic Community Health Study/Study of Latinos. We compared the prevalence of using antiplatelet therapy, lipid-lowering therapy and antihypertensive therapy by PAD and coronary artery disease status. Among those with PAD, we studied factors associated with taking cardiovascular medications, including demographic and socioeconomic factors, acculturation, access to health care and comorbidities, using multivariable regression models. The overall prevalence for individuals with PAD taking antiplatelet therapy, lipid-lowering therapy and, among hypertensive individuals, antihypertensive therapy was 31%, 26% and 57%, respectively. Individuals of Mexican background had the lowest use for all classes of cardiovascular medications. Older age, number of doctor visits and existing hypertension and diabetes mellitus were significantly associated with taking cardiovascular therapies in adjusted models. Compared with those with PAD alone, individuals with PAD and concurrent coronary artery disease were 1.52 (95% CI, 1.20-1.93) and 1.74 (1.30-2.32) times more likely to use antiplatelet agents and statins according to multivariable analysis. No significant difference of antihypertensive medication use was found among PAD patients with or without coronary artery disease. Conclusions Hispanic/Latino individuals with known PAD underuse cardiovascular medications recommended in clinical guidelines. More efforts should be directed to improve treatment in this important group.

19.
J Clin Invest ; 130(11): 5688-5702, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-32701509

RESUMO

Males and females differ in body composition and fat distribution. Using a mouse model that segregates gonadal sex (ovaries and testes) from chromosomal sex (XX and XY), we showed that XX chromosome complement in combination with a high-fat diet led to enhanced weight gain in the presence of male or female gonads. We identified the genomic dosage of Kdm5c, an X chromosome gene that escapes X chromosome inactivation, as a determinant of the X chromosome effect on adiposity. Modulating Kdm5c gene dosage in XX female mice to levels that are normally present in males resulted in reduced body weight, fat content, and food intake to a degree similar to that seen with altering the entire X chromosome dosage. In cultured preadipocytes, the levels of KDM5C histone demethylase influenced chromatin accessibility (ATAC-Seq), gene expression (RNA-Seq), and adipocyte differentiation. Both in vitro and in vivo, Kdm5c dosage influenced gene expression involved in extracellular matrix remodeling, which is critical for adipocyte differentiation and adipose tissue expansion. In humans, adipose tissue KDM5C mRNA levels and KDM5C genetic variants were associated with body mass. These studies demonstrate that the sex-dependent dosage of Kdm5c contributes to male/female differences in adipocyte biology and highlight X-escape genes as a critical component of female physiology.

20.
Metabolism ; 111: 154321, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32712219

RESUMO

BACKGROUND: Lean muscle plays critical roles in physical functioning and metabolism. However, little is known regarding associations between muscle and mortality in adults. OBJECTIVE: The purpose was to evaluate associations between abdominal muscle quantity (area) and quality (density) with risk of all-cause mortality in a diverse cohort free of cardiovascular disease. DESIGN: Data were taken from the Abdominal Body Composition, Inflammation, and Cardiovascular Disease ancillary study of the Multi-Ethnic Study of Atherosclerosis prospective cohort study. Participants were adults (45-85 years) free of extant cardiovascular disease, and of Hispanic, African American, Chinese, or Caucasian descent. Of the original 6814 MESA participants, a random, representative sample (n = 1974) participated in the ancillary body composition study. Abdominal muscle area and density were measured from computed tomography scans spanning L2-L4. Muscle density was measured as attenuation in Hounsfield units, and area was quantified as cm2. Gender-stratified cox proportional hazard models assessed the risk of all-cause mortality across gender-specific quartiles of muscle area and density adjusting for confounders, with area and density entered simultaneously. RESULTS: At baseline, the mean age for men (n = 946) and women (n = 955) was 61.5 and 62.5 years and median follow-up time was 10.6 and 10.9 years, respectively. Muscle density was inversely associated with mortality, with the highest quartile of density showing a 73% reduction in risk for men (HR = 0.27, 95% CI = 0.14-0.51; p-trend<0.001) and 57% reduction for women (HR = 0.43, 95% CI = 0.18-1.01; p-trend = 0.04) compared to the lowest quartile when adjusting for mortality risk factors, lifestyle, BMI and visceral fat. There was no association between muscle area and all-cause mortality for men (p-trend = 0.58) or women (p-trend = 0.47). CONCLUSIONS: Greater abdominal muscle density, but not muscle area, is associated with markedly lower risk of all-cause mortality across a decade of follow up. Muscle quality may be a powerful predictor of mortality in community dwelling adults.


Assuntos
Músculos Abdominais/fisiopatologia , Aterosclerose/mortalidade , Aterosclerose/fisiopatologia , Composição Corporal/fisiologia , Grupos Étnicos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
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