The impact of birth weight on cardiovascular disease risk in the Women's Health Initiative.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is among the leading causes of morbidity and mortality worldwide. Traditional risk factors predict 75-80% of an individual's risk of incident CVD. However, the role of early life experiences in future disease risk is gaining attention. The Barker hypothesis proposes fetal origins of adult disease, with consistent evidence demonstrating the deleterious consequences of birth weight outside the normal range. In this study, we investigate the role of birth weight in CVD risk prediction. METHODS AND RESULTS: The Women's Health Initiative (WHI) represents a large national cohort of post-menopausal women with 63,815 participants included in this analysis. Univariable proportional hazards regression analyses evaluated the association of 4 self-reported birth weight categories against 3 CVD outcome definitions, which included indicators of coronary heart disease, ischemic stroke, coronary revascularization, carotid artery disease and peripheral arterial disease. The role of birth weight was also evaluated for prediction of CVD events in the presence of traditional risk factors using 3 existing CVD risk prediction equations: one body mass index (BMI)-based and two laboratory-based models. Low birth weight (LBW) (<6 lbs.) was significantly associated with all CVD outcome definitions in univariable analyses (HR = 1.086, p = 0.009). LBW was a significant covariate in the BMI-based model (HR = 1.128, p < 0.0001) but not in the lipid-based models. CONCLUSION: LBW (<6 lbs.) is independently associated with CVD outcomes in the WHI cohort. This finding supports the role of the prenatal and postnatal environment in contributing to the development of adult chronic disease.

Maternal lipid levels during pregnancy and gestational diabetes: a systematic review and meta-analysis.

BACKGROUND: Lipid levels during pregnancy in women with gestational diabetes mellitus (GDM) have been extensively studied; however, it remains unclear whether dyslipidaemia is a potential marker of preexisting insulin resistance. OBJECTIVE: To evaluate the relationship between lipid measures throughout pregnancy and GDM. SEARCH STRATEGY: We searched PubMed-MedLine and SCOPUS (inception until January 2014) and reference lists of relevant studies. SELECTION CRITERIA: Publications describing original data with at least one raw lipid (total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], or triglyceride) measurement during pregnancy in women with GDM and healthy pregnant controls were retained. DATA COLLECTION AND ANALYSIS: Data extracted from 60 studies were pooled and weighted mean difference (WMD) in lipid levels was calculated using random effects models. Meta-regression was also performed to identify sources of heterogeneity. MAIN RESULTS: Triglyceride levels were significantly elevated in women with GDM compared with those without GDM (WMD 30.9, 95% confidence interval [95% CI] 25.4-36.4). This finding was consistent in the first, second and third trimesters of pregnancy. HDL-C levels were significantly lower in women with GDM compared with those without GDM in the second (WMD -4.6, 95% CI -6.2 to -3.1) and third (WMD -4.1, 95% CI -6.5 to -1.7) trimesters of pregnancy. There were no differences in aggregate total cholesterol or LDL-C levels between women with GDM and those without insulin resistance. AUTHOR'S CONCLUSIONS: Our meta-analysis shows that triglycerides are significantly elevated among women with GDM compared with women without insulin resistance and this finding persists across all three trimesters of pregnancy.

Efficacy and safety of dalcetrapib in type 2 diabetes mellitus and/or metabolic syndrome patients, at high cardiovascular disease risk.

AIMS: Mixed dyslipidaemia, characterized by low levels of high-density lipoprotein cholesterol (HDL-C) and high levels of triglycerides, is common in patients with type 2 diabetes mellitus (T2DM) and/or metabolic syndrome. Dalcetrapib effectively increases HDL-C levels by modulating cholesteryl ester transfer protein (CETP) activity. The aim of this analysis was to investigate the lipid modifying efficacy and safety of dalcetrapib in patients with T2DM and/or metabolic syndrome. METHODS: Post hoc analysis of dalcetrapib therapy in five placebo-controlled, Phase II trials (4-48 weeks of duration) involving T2DM and/or metabolic syndrome, in dyslipidaemic patients with coronary heart disease (CHD) or CHD risk equivalent. RESULTS: Both in patients with and without T2DM and/or metabolic syndrome, dalcetrapib decreased CETP activity by 26-58% and increased HDL-C levels by 23-34%, depending on dose and duration of treatment. Dalcetrapib did not significantly affect low-density lipoprotein cholesterol (LDL-C) or apolipoprotein B levels. Treatment with dalcetrapib was generally well tolerated with a similar number of adverse events reported between patient groups and between those receiving dalcetrapib compared with placebo. CONCLUSIONS: Dalcetrapib similarly decreased CETP activity and increased HDL-C levels in patients with and without T2DM or metabolic syndrome; the ongoing Phase III dal-OUTCOMES study will help to determine if dalcetrapib's improvement in lipid levels also reduces cardiovascular morbidity and mortality.

Underutilisation of cardiovascular medications among at-risk individuals.

AIMS: Guidelines recommend antihypertensive, lipid-lowering and/or antiplatelet therapy for prevention of cardiovascular disease (CVD). This study examined the utilisation of cardiovascular therapies among individuals at CVD risk to assess adherence to guidelines. METHODS: Respondents to the SHIELD study were classified based on National Cholesterol Education Program Adult Treatment Panel III risk categories. High coronary heart disease (CHD) risk (n = 7510) was defined as self-reported diagnosis of heart disease/heart attack, narrow or blocked arteries, stroke or diabetes; moderate risk (n = 4823) included respondents with > or = 2 risk factors (i.e., men > 45 years, women > 55 years, hypertension, low high-density lipoprotein cholesterol, smoking and family history of CHD); and low risk (n = 5307) was 0-1 risk factor. Respondents reporting a myocardial infarction, stroke or revascularisation at baseline (prior CVD event) (n = 3777), those reporting a new CVD event during 2 years of follow up (n = 953), and those with type 2 diabetes mellitus (n = 3937) were evaluated. The proportion of respondents reporting treatment with lipid-lowering, antiplatelet or antihypertensive agents was calculated. RESULTS: Utilisation of lipid-lowering therapy was low (< or = 25%) in each group. Prescription antithrombotic therapy was minimal among respondents with prior CVD events, but 47% received antihypertensive medication. No use before or after a new CVD event was reported by 36% of respondents for lipid-lowering, 32% for antithrombotic and > 50% for antihypertensive medications. CONCLUSIONS: More than 50% of at-risk respondents and > 33% of respondents with new CVD events were not taking CVD therapy as recommended by guidelines.

Anthropogenic modification of forests means only 40% of remaining forests have high ecosystem integrity.

Many global environmental agendas, including halting biodiversity loss, reversing land degradation, and limiting climate change, depend upon retaining forests with high ecological integrity, yet the scale and degree of forest modification remain poorly quantified and mapped. By integrating data on observed and inferred human pressures and an index of lost connectivity, we generate a globally consistent, continuous index of forest condition as determined by the degree of anthropogenic modification. Globally, only 17.4 million km2 of forest (40.5%) has high landscape-level integrity (mostly found in Canada, Russia, the Amazon, Central Africa, and New Guinea) and only 27% of this area is found in nationally designated protected areas. Of the forest inside protected areas, only 56% has high landscape-level integrity. Ambitious policies that prioritize the retention of forest integrity, especially in the most intact areas, are now urgently needed alongside current efforts aimed at halting deforestation and restoring the integrity of forests globally.

Sex ratio: adaptive response to population fluctuations in pandalid shrimp.

Pandalus jordani is a protandrous (sequential) hermaphrodite. Populations show large year-to-year variation in age composition. In response to this variation, individuals alter the age at which they change sex. This response is predicted by a genetic model that assumes that an individual shrimp maximizes its genetic contribution to the next generation.

Emerging innovative therapeutic approaches targeting PCSK9 to lower lipids.

Statins are established therapies for cardiovascular disease prevention and ezetimibe has recently been shown to modestly reduce cardiovascular events when added to background statin therapy. Yet here remains a clear unmet need for additional therapies aimed at lowering low density lipoprotein cholesterol (LDL-C) to further reduce cardiovascular risk. Multiple strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have emerged as effective modalities for LDL-C lowering. PCSK9 monoclonal antibodies are the farthest along in clinical development and alirocumab and evolocumab were approved for clinical use by regulatory agencies in 2015. In addition to robust LDL-C lowering (nearly 50-65% from baseline), they improve other lipid parameters as well. Adverse events associated with these medications are minimal. Importantly, they improve clinical cardiovascular disease outcomes, although long-term study results are awaited. Cost may be an important limiting factor in their use and we propose two possible solutions which can potentially curtail cost.

A novel telephone-based system for management of secondary prevention to a low-density lipoprotein cholesterol < or = 100 mg/dl.

Unfortunately, lipid-lowering drug therapy remains underutilized in clinical practice, and few secondary prevention patients achieve the low-density lipoprotein (LDL) cholesterol level (< or = 100 mg/dl) recommended by the National Cholesterol Education Program. To improve patient management, a telephone-based computerized system primarily managed by dietitians was implemented in one of our cardiology clinics. Lipid results from all lipid and cardiology referrals and patients admitted to the cardiology service at 1 hospital are managed through this system. Patients are contacted via computer-generated postcards and the dietitians every 3 to 6 months. At baseline (September 1, 1994, through August 31, 1995; n = 1,969), 34% and 66% had LDL cholesterol < or = 100 and < or = 130 mg/dl, respectively. By September 1, 1997, to August 31, 1998 (n = 2,827), the proportion of patients with LDL cholesterol < or = 100 mg/dl had increased to 61%, and 89% had LDL cholesterol < or = 130 mg/dl. Statin use increased from 47% to 85% of patients. By 1997 to 1998, 74% and 40% of patients received statin doses that would, on average, produce a 34% and 41% reduction in LDL cholesterol, respectively. Whether a patient had LDL cholesterol < or = 100 mg/dl was not predicted by patient characteristics, drugs given, or by medication insurance coverage.

Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment.

OBJECTIVE: We examined the change in menopausal symptoms in response to 24 weeks of isoflavone-rich (80.4 mg/day) and isoflavone-poor (4.4 mg/day) soy protein isolate treatment in perimenopausal women. DESIGN: In this double-blind 24-week study, 69 women were randomized to treatment: isoflavone-rich soy protein (n = 24), isoflavone-poor soy protein (n = 24), or whey protein control (n = 21). A Menopausal Index was used to assess change in hot flushes and night sweats, as well as other symptoms, at baseline, week 12, and week 24. RESULTS: Repeated measures analysis of variance indicated no treatment effect on change in hot flush (p = 0.18) and night sweat (p = 0.92) frequency, whereas there was a significant decline in hot flush (p = 0.0003) and night sweat (p = 0.0007) frequency with time in all treatment groups. Chi2 analyses indicated no treatment effect on severity of hot flushes or night sweats at any time point, as well as no treatment effect on frequency or severity of other vasomotor symptoms. At the completion of the study, we found no treatment effect on retrospective perception of frequency, duration, or severity of hot flushes or night sweats. Since time had a significant effect on symptoms with all groups reporting a decline in overall symptoms, this indicated either a placebo effect or simply an improvement in symptoms during the study. CONCLUSION: In this study, we found no evidence that isoflavone-rich or isoflavone-poor soy protein provided relief of vasomotor or of other menopausal symptoms.

The prevention of cardiovascular disease. Emphasis on secondary prevention.

Atherosclerosis is a progressive disease affecting all major arteries. Clinical evidence of atherosclerosis increases the risk of subsequent morbid and mortal events fivefold to sevenfold over the next 5 to 10 years. The same risk factors contribute to the initial development of CVD events as to their recurrence. Both coronary and noncoronary events, such as stroke or PAD, reflect the severity of the underlying atherosclerotic process and strongly predict future excess CVD morbidity and mortality. Short-term and long-term survival depends on modifying the risk factors that contribute to CVD events. Although absolute proof of benefit for secondary prevention does not exist for all risk factors, the data from primary prevention trials and the secondary prevention trials that have been done argue strongly for aggressive intervention. Benefit has been demonstrated for smoking cessation, cholesterol reduction, and blood pressure control. Selected patients may benefit from additional medical, procedural, or surgical interventions to prolong life, such as beta-blocking agents, aspirin, or carotid endarterectomy. Many secondary prevention measures are a cost-effective way to reduce the substantial morbidity and mortality due to CVD. Contrary to primary prevention, even modest treatment effects from secondary prevention efforts can benefit large numbers of patients. Finally, secondary prevention may be more successful because patients with clinical evidence of CVD may be more highly motivated than their healthy counterparts to make and maintain lifestyle changes.

Changes in empowerment: effects of participation in a lay health promotion program.

The Camp Health Aide Program is a lay health promotion program for migrant and seasonal farmworkers. The program increases access to health care while facilitating leadership development and empowerment of individual farmworkers through training and experience as lay health promoters (camp health aides [CHAs]). This article describes a study which documents impacts on the CHAs of working as lay health promoters in terms of changes in personal empowerment. The authors developed a working definition of personal empowerment and interviewed 27 CHAs at three program sites (Arizona, New Jersey, and Florida) at three different times. CHAs are grouped in five descriptive categories reflecting varying degrees of change in empowerment over this period. Of the total group of 27 CHAs, 24 exhibited some increase in personal empowerment during the study period. These changes are described in detail, and implications are discussed.

Impact strength of acrylic resin denture base materials with surface defects.

The first part of this study involved the development of a method for evaluating the effect of small surface defects (3.0 microns-80.0 microns) on the impact strength of acrylic denture base materials. The method was used to compare the properties of 12 denture base materials, some of which are described as "high-impact strength" products. The defects were introduced by drawing the specimens over abrasive papers of varying grit sizes or by notching with a craft knife. Flexural toughness tests were also carried out in order to evaluate the materials under both rapid (impact) and slow (flexural) rate test conditions. The impact resistance of acrylic resins was significantly reduced by the presence of very small surface defects (e.g., < 16 microns), and this was particularly noticeable for so-called high-impact resins. The latter have values of impact strength only slightly higher than standard acrylic products when defects are present. Testing "notched" specimens with small surface defects was a simple method of obtaining reproducible results. This test was sensitive enough to differentiate among several types of currently available denture base resins.

The provision of prostheses for patients with severe limitation in opening of the mouth.

The problem of providing prostheses for patients with restricted mandibular opening is not well reported, either in current texts on prosthodontics or in the literature. This report features two patients who suffer from severe and chronic forms of the disorder. The aim of the article is to provide some useful hints with respect to the prosthetic management of such patients.

Chlorhexidine gluconate--the solution for dental problems.

Rarely is a chemical agent so effective with so few contra-indications as is chlorhexidine. It has many oral applications, the main ones being the control of plaque and gingivitis. Due to the constraints on oral hygiene in animals, its benefits and indications are especially appropriate to veterinary dental cases. Its full potential is not being realised.

Ethnic differences in the relationship between birth weight and type 2 diabetes mellitus in postmenopausal women.

AIM: The objective of this study is to examine the relationship between self-reported birth weight and the adult occurrence of type 2 diabetes mellitus in a large multi-ethnic population of women. METHODS: Baseline data from the Women's Health Initiative Observational Study [n=75,993] was used to examine the association between participant birth weight category and prevalent type 2 diabetes mellitus. Models were adjusted for age, ethnicity, body mass index and other pertinent risk factors. Sub-analyses were performed stratifying by ethnicity. RESULTS: There was a strong inverse association between birth weight and type 2 diabetes mellitus with a birth weight of <6 pounds (lbs) (OR: 1.16, 95% CI: 1.01, 1.33) significantly associated with an increased risk of type 2 diabetes mellitus and a birth weight of ≥10 lbs (OR: 0.72, 95% CI: 0.57, 0.92) associated with a decreased risk of type 2 diabetes mellitus compared to women who reported their birth weight between 7 and 8 lbs 15 ounces (oz). Stratifying by ethnicity, the inverse association between birth weight and type 2 diabetes mellitus was only apparent in White women, but not Black, Hispanic or Asian women. CONCLUSION: Lower birth weight was associated with increased T2D risk in American White and Black post-menopausal women.

Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: a genome-wide association study of 13,372 participants.

BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE: To identify novel genetic variants associated with resting heart rate in African Americans. METHODS: Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P≤2.5×10(-8)). RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS: An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.