Microaxial circulatory support for percutaneous coronary intervention: A systematic review and meta-analysis.

BACKGROUND: Microaxial circulatory support devices have been used to support patients treated with percutaneous coronary intervention (PCI) for acute myocardial infarction complicated by cardiogenic shock (AMICS). The purpose of this systematic review and meta-analysis was to pool and analyze the existing evidence on the baseline characteristics, periprocedural data, and outcomes of microaxial support before and after PCI in AMICS. METHODS: An electronic database search was performed to identify all cohort studies on Impella and PCI for cardiogenic shock in the English language. A total of five articles comprising 543 patients were included. These patients received microaxial support either before (pre-PCI) or after (post-PCI) undergoing PCI. Comparative analyses were done between both groups. RESULTS: The mean patient age was 66 years [95% Confidence Interval (58-74)], and 22% (89/396) of patients were female. ST-elevation myocardial infarctions (MI) comprised 64% (44-80) of MIs and 50% (44-56) of MIs involved the left anterior descending artery. The mean number of diseased vessels was 2.21 (1.62-2.80). The mean left ventricular ejection fraction was 31% (23.4-38.6). The mean arterial pressure was 66.3 mm Hg (54.1-78.5). Mean serum lactate [6.1 mmol/L (3.3-8.9)] and serum creatinine [1.4 mg/dl (1.0-1.7)] were similar between groups. 30-day mortality was lower in the pre-PCI group [41% (34%-49%)] compared to the post-PCI group [61% (42%-77%), p < 0.01]. Pooled Kaplan-Meier analysis showed better early survival in the pre-PCI group (p < 0.001). CONCLUSION: Patients presenting with AMICS were similar at baseline in both pre-PCI and post-PCI groups. Nevertheless, pre-PCI group showed better early survival compared to post-PCI group.

Utility of Recipient Cardiothoracic Ratio in Predicting Delayed Chest Closure after Heart Transplantation.

BACKGROUND: Predicted cardiac mass (PCM) has been well validated for size matching donor hearts to heart transplantation recipients. We hypothesized that cardiothoracic ratio (CTR) could be reflective of recipient-specific limits of oversizing, and sought to determine the utility of donor to recipient PCM ratio (PCMR) and CTR in predicting delayed chest closure after heart transplantation. METHODS: A retrospective review of prospectively collected data on 38 consecutive heart transplantations performed at our institution from 2017 to 2020 was performed. Donor and recipient PCM were estimated using Multi-Ethnic Study of Atherosclerosis predictive models. Receiver operating characteristic analysis was performed to determine the discriminatory power of the ratio of PCMR to CTR in predicting delayed sternal closure. RESULTS: Of the 38 patients, 71.1% (27/38) were male and the median age at transplantation was 58 (interquartile range [IQR]: 47-62) years. Ischemic cardiomyopathy was present in 31.6% of recipients (12/38). Median recipient CTR was 0.63 [IQR: 0.59-0.66]. Median donor to recipient PCMR was 1.07 [IQR: 0.96-1.19], which indicated 7% oversizing. Thirteen out of 38 (34.2%) underwent delayed sternal closure. Primary graft dysfunction occurred in 15.8% (6/38). PCMR/CTR showed good discriminatory power in predicting delayed sternal closure [area under the curve: 80.4% (65.3-95.6%)]. PCMR/CTR cut-off of 1.7 offered the best trade-off between the sensitivity (69.6%) and specificity (91.7%). CONCLUSION: CTR could be helpful in guiding the recipient-specific extent of oversizing donor hearts. Maintaining the ratio of PCMR to CTR below 1.7 could avoid excessive oversizing of the donor heart.

Outcomes of percutaneous temporary biventricular mechanical support: a systematic review.

Percutaneous biventricular assist devices (BiVAD) are a recently developed treatment option for severe cardiogenic shock. This systematic review sought to identify indications and outcomes of patients placed on percutaneous BiVAD support. An electronic search was performed to identify all appropriate studies utilizing a percutaneous BiVAD configuration. Fifteen studies comprising of 20 patients were identified. Individual patient survival and outcomes data were combined for statistical analysis. All 20 patients were supported with a microaxial LVAD, 12/20 (60%) of those patients were supported with a microaxial (RMA) right ventricular assist device (RVAD), and the remaining 8/20 (40%) patients were supported with a centrifugal extracorporeal RVAD (RCF). All patients presented with cardiogenic shock, and of these, 12/20 (60%) presented with a non-ischemic etiology vs 8/20 (40%) with ischemic disease. For the RMA group, RVAD support was significantly longer [RMA 5 (IQR 4-7) days vs RCF 1 (IQR 1-2) days, p = 0.03]. Intravascular hemolysis post-BiVAD occurred in three patients (27.3%) [RMA 3 (33.3%) vs RCF 0 (0%), p = 0.94]. Five patients received a durable left ventricular assist device, one patient received a total artificial heart, and one patient underwent a heart transplantation. Estimated 30-day mortality was 15.0%, and 78.6% were discharged alive. Both strategies for percutaneous BiVAD support appear to be viable options for severe cardiogenic shock.

Tricuspid regurgitation associated with implantable electrical device insertion: A systematic review and meta-analysis.

BACKGROUND: Implantable cardioverter defibrillator (ICD) and permanent pacemaker (PPM) lead placement may worsen or result in tricuspid regurgitation (TR). While the association between lead placement and the incidence of TR has been established, current understanding of this problem remains incomplete. This systematic review and meta-analysis sought to pool the existing evidence to better understand the occurrence and severity of TR associated with cardiac implantable electrical device (CIED) insertion. METHODS: An electronic search was performed to identify all relevant studies published from 2000 to 2018. Overall, 15 studies were selected for the analysis comprising 4019 patients with data reported on TR development following ICD or PPM lead placement. Demographic information, perioperative clinical variables, and clinical outcome measures, including pre and postoperative echocardiographic TR grade changes, were extracted and pooled for systematic review. RESULTS: Mean patient age was 69 years [95% CI: 64.62-73.59], and 63% [95% CI: 57-68] were male. Devices implanted included ICD in 57% [95%CI: 43-70] and PPM in 41% [95%CI: 31-52]. The most common indications for pacemaker implantation were sick sinus syndrome in 22% [95% CI: 22-37] and AV block in 21% [95%CI:12-34. The commonest indications for ICD implantation were primary and secondary prevention of sudden cardiac death. Atrial fibrillation was present in 37% [95%CI: 28-46] and congestive heart failure in 15% [95%CI: 2-57]. Baseline distribution of TR grades were as follows: grade 0/1 TR in 89% [95%CI: 82-93], grade 2 TR in 8% [95%CI: 5-13], grade 3 TR in 2% [95%CI: 0-7] and grade 4 TR in 2% [95%CI: 1-4]. Post-procedure, grade 0/ 1 TR decreased to 68% [95% CI: 51-81] (p < 0.01), grade 2 TR increased to 21% [15-28] (p < 0.01), grade 3 TR increased to 13% [95%CI: 5-32] (p = 0.02), and grade 4 TR increased to 7% [95%CI: 5-9] (p < 0.01). CONCLUSION: ICD and PPM lead placement is associated with increased TR post-procedure. Further studies are warranted to evaluate changes in TR grade in the long term.

Utilization of extracorporeal life support for diffuse alveolar damage and diffuse alveolar hemorrhage: A systematic review.

Modern extracorporeal life-support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH); however, reports in the literature remain scarce. We sought to pool existing evidence to better characterize ECLS use in these patients. An electronic search was conducted to identify all studies in the English literature reporting the use of ECLS for DAD/DAH. Thirty-two articles consisting of 38 patients were selected, and patient-level data were extracted and pooled for analysis. Median patient age was 36 [IQR: 27, 48] years, and the majority (63.2%) were female. Most common etiological factors included granulomatosis with polyangiitis (8/38, 21.1%), systemic lupus erythematosus (8/38, 21.1%), Goodpasture's syndrome (4/38, 10.5%), and microscopic polyangiitis (4/38, 10.5%). Immunologic markers included anti-neutrophil cytoplasmic antibody (ANCA) in 15/38 (39.5%), anti-nuclear antibody (ANA) in 6/38 (15.8%), and anti-glomerular basement membrane (anti-GBM) antibodies in 4/38 (10.5%). DAH was present in 32/38 (84.2%) of cases and DAD without evidence of DAH was present in 6/38 (15.8%) of cases. ECLS strategies included extracorporeal membrane oxygenation of veno-venous type (VV-ECMO) in 28/38 (73.7%), veno-arterial type (VA-ECMO) in 5/38 (13.2%), and one case of right ventricular assist device with oxygenator (RVAD-ECMO). Heparin was utilized in 18/38 (47.4%) of cases with no difference in use between DAH versus no DAH (P = .46) or VA- versus VV-ECLS (P = 1). Median duration of ECLS was 10 [5, 14] days. Pre- versus post-ECLS comparison of blood gases showed improvement in median PaO2 (49 [45, 59] mm Hg vs. 80 [70, 99] mm Hg, P < .001), PaO2:FiO2 ratio (48.2 [41.4, 54.8] vs. 182.0 [149.4, 212.2], P < .01), and pulse oximetry values (76% [72, 80] vs. 96% [94, 97], P = .086). Overall, 94.7% (36/38) of patients survived to decannulation while 30-day mortality was 10.5% (4/38) with no differences between VA- and VV-ECMO (P = 1 and P = .94, respectively). DAD/DAH occurs in a younger, predominantly female population, and tends to be associated with systemic autoimmune processes. ECLS, independent of its type, appears to result in favorable short-term survival.

Continuous-flow LVAD exchange to a different pump model: Systematic review and meta-analysis of the outcomes.

Despite improved outcomes of modern continuous-flow left ventricular assist devices (CF-LVADs), device exchange is still needed for various indications. While the majority of CF-LVADs are exchanged to the same model, exchange to a different pump model is occasionally warranted. In this meta-analysis, we sought to consolidate the existing evidence to better elucidate the indications and outcomes in these cases. A comprehensive systematic search of adult patient cohorts who underwent CF-LVAD exchange to a different CF-LVAD model was performed. Study-level data from 10 studies comprising 98 patients were extracted and pooled for analysis. Mean patient age was 58 (95% CI: 48-65) and 81% were male. Indication for initial CF-LVAD was ischemic cardiomyopathy in 45% (34-57). Initial device was HeartMate II LVAD (HMII) in 93 (94.9%) and HeartWare HVAD (HW) in 5 (5.1%) patients. After mean CF-LVAD support time of 18.8 (15.2-22.4) months, exchange indications included thrombosis in 71% (43-89), infection in 21% (8-47) and device malfunction in 12% (7-21). HMII to HW exchange occurred in 53 (54.1%) patients, HMII to HeartMate III (HM3) in 32 (32.7%), and HM II to either HW or HM3 in 13 (13.2%) patients. Postoperatively, right ventricular assist device was required in 16% (8-32). Overall, 20% (8-40) of patients experienced a stroke, while HW patients had a significantly higher stroke incidence than HM3 patients (HW: 21% (8-47) vs. HM3: 5% (1-24), P < .01). Overall 30-day mortality was 10% (6-17), while HW had a significantly worse 30-day mortality than HM3 (HW: 13% (7-24) vs. HM3: 5% (1-24), P = .03). Following device exchange from a different CF-LVAD model, HM3 is associated with lower stroke and higher survival when compared to HW.

Very High-Dose Furosemide Continuous Infusions: A Case Series.

BACKGROUND: There is paucity of data evaluating the efficacy and safety of very high-dose furosemide continuous infusions (≥40 mg/h) for volume removal. This infusion is a novel strategy of loop diuretic administration that may add valuable data to current literature. METHODS AND RESULTS: This was a retrospective chart review. Patients were eligible for inclusion if prescribed a very high-dose furosemide infusion (defined as ≥40 mg/h, up to 240 mg/h) from April 1, 2017, to January 1, 2019, at Thomas Jefferson University Hospital. Data collected included the change in cumulative urine output, net urine output, incidence of acute kidney injury, occurrences of hypotension, electrolyte abnormalities, body weight, and ototoxicity. Twenty-two patients were included in this analysis. The median change in 24-hour urine output from before to after very high-dose continuous furosemide infusion increased from 1193 mL at 24 hours before infusion initiation to 3518 mL at 24 hours after infusion initiation (P < .01). Serum creatinine increased 24 hours after infusion initiation but decreased within 48 hours. There were no electrolyte abnormalities. Out of 22 patients, only 2 had an occurrence of hypotension. No patients were reported to have ototoxicity. CONCLUSIONS: Very high-dose furosemide continuous infusions provide a significant increase in diuresis without worsening renal function, disturbing electrolytes, or increasing the risk of ototoxicity. Further studies are necessary to examine the efficacy and safety of this novel strategy.

Association between iq'mik smokeless tobacco use and cardiometabolic risk profile among Yup'ik Alaska Native people.

OBJECTIVE: The traditional lifestyle of Yup'ik Alaska Native people, including a diet abundant in marine-based foods and physical activity, may be cardio-protective. However, iq'mik, a traditional form of smokeless tobacco used by >50% of Yup'ik adults, could increase cardiometabolic (CM) risk. Our objective was to characterize the associations between iq'mik use and biomarkers of CM status (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], systolic blood pressure [SBP] and diastolic blood pressure [DBP], glycated hemoglobin [HbA1c], fasting blood glucose [FBG], waist circumference [WC], and body mass index [BMI]). DESIGN: We assessed these associations using data from a cross-sectional sample of Yup'ik adults (n = 874). Current iq'mik use, demographic, and lifestyle data were collected through interviews. Fasting blood samples were collected to measure LDL-C, HDL-C, TG, HbA1c, and FBG. SBP, DBP, WC, and BMI were obtained by physical examination. We characterized the association between current iq'mik use and continuous biomarkers of CM status using multiple approaches, including adjustment for measures of Yup'ik lifestyle and a propensity score. RESULTS: Based on either adjustment method, current iq'mik use was significantly and positively associated with at least 5% higher HDL-C, and significantly associated but in an inverse direction with multiple biomarkers of CM status including 7% lower TG, 0.05% lower HbA1c, 2% lower FBG, 4% lower WC, and 4% lower BMI. Observed associations for LDL-C, SBP, and DBP varied by adjustment method. CONCLUSIONS: This inverse association between iq'mik use and cardiometabolic risk status has not been previously reported. Additional research is needed to replicate these findings and explore physiological mechanisms and/or confounding factors.

Clinical Medical Librarian Licensure: Pros versus Cons.

In hospitals and clinics, anyone who "touches" a patient has a license authorizing them to do so-from the phlebotomist to the cardiologist, from the genetic counselor to the social worker, and so on, except for the clinical medical librarian. This column discusses the intent versus the realities of occupational licensure for clinical medical librarians and provides recommendations for next steps.

Carnitine palmitoyltransferase 1A P479L and infant death: policy implications of emerging data.

Carnitine palmitoyltransferase 1 isoform A (CPT1A) is a crucial enzyme for the transport of long-chain fatty acids into the mitochondria. The CPT1A p.P479L variant is found in high frequencies among indigenous populations residing on the west and north coasts of Alaska and Canada and in northeast Siberia and Greenland. Epidemiological studies have reported a statistical association between P479L homozygosity and infant death in Alaska Native and Canadian Inuit populations. Here, we review the available evidence about the P479L variant and apply to these data the epidemiological criteria for assessing causal associations. We found insufficient evidence to support a causal association with infant death and, further, that if a causal association is present, then the genotype is likely to be only one of a complex set of factors contributing to an increased risk of infant death. We conclude that additional research is needed to clarify the observed association and to inform effective preventative measures for infant death. In light of these findings, we discuss the policy implications for public health efforts because policies based on the observed association between P479L homozygosity and infant death data are premature.Genet Med advance online publication 26 January 2017.

Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

A survey of tuberculosis infection control practices at the NIH/NIAID/DAIDS-supported clinical trial sites in low and middle income countries.

BACKGROUND: Health care associated transmission of Mycobacterium tuberculosis (TB) is well described. A previous survey of infection control (IC) practices at clinical research sites in low and middle income countries (LMIC) funded by the National Institute of Allergy and Infectious Diseases (NIAID) conducting HIV research identified issues with respiratory IC practices. A guideline for TB IC based on international recommendations was developed and promulgated. This paper reports on adherence to the guideline at sites conducting or planning to conduct TB studies with the intention of supporting improvement. METHODS: A survey was developed that assessed IC activities in three domains: facility level measures, administrative control measures and environmental measures. An external site monitor visited each site in 2013-2014, to complete the audit. A central review committee evaluated the site-level survey and results were tabulated. Fisher's exact test was performed to determine whether there were significant differences in practices at sites that had IC officers versus sites that did not have IC officers. Significance was assessed at p

Outcomes of a Pilot Intervention Study for Young Adults at Risk for Cardiovascular Disease Based on Their Family History.

BACKGROUND: Lifestyle choices have a significant impact on cardiovascular disease (CVD) risk. Interventions to promote a heart-healthy lifestyle in young adults at long-term high risk for CVD are needed to decrease the burden of CVD. However, few interventions with this purpose have been developed. OBJECTIVE: The objective of this study was to examine the effect of a pilot intervention on young adults with a family history of CVD that used 3-generation pedigrees, risk factor information, and counseling on heart disease knowledge, perceived CVD risk, and intention to engage in a heart-healthy lifestyle. METHODS: A pretest-posttest design, with within-group analysis, was used to examine the effect of the intervention. Paired t test and Wilcoxon signed rank tests were used to examine the changes in heart disease knowledge, perceived risk, and behavioral intention from baseline to postintervention. The Cohen d was calculated to examine the effect of the intervention on study measures. In addition, Spearman ρ was used to examine the associations between postintervention perceived risk, postintervention behavioral intention, and family history. RESULTS: The sample for the pilot study included 15 mostly white and mostly female healthy young adults between the ages of 18 and 25 years. The intervention was effective at increasing CVD knowledge (P = .02) and had a medium effect on perceived risk and intention to engage in a heart-healthy lifestyle (Cohen d, 0.48-0.58). There were significant associations between postintervention perceived risk and postintervention intention to exercise and the participants' family history of coronary heart disease (r = 0.62, P = .014 and r = 0.55, P = .035, respectively). CONCLUSIONS: Interventions are needed to increase individuals' awareness of their long-term CVD risk and to improve their ability to make lifestyle changes. Although this intervention was only tested in a small sample, it shows promise to improve heart disease knowledge and perceived lifetime CVD risk and may effect longer-term risk for CVD.

Characterising the reproducibility and reliability of dietary patterns among Yup'ik Alaska Native people.

FFQ data can be used to characterise dietary patterns for diet-disease association studies. In the present study, we evaluated three previously defined dietary patterns--'subsistence foods', market-based 'processed foods' and 'fruits and vegetables'--among a sample of Yup'ik people from Southwest Alaska. We tested the reproducibility and reliability of the dietary patterns, as well as the associations of these patterns with dietary biomarkers and participant characteristics. We analysed data from adult study participants who completed at least one FFQ with the Center for Alaska Native Health Research 9/2009-5/2013. To test the reproducibility of the dietary patterns, we conducted a confirmatory factor analysis (CFA) of a hypothesised model using eighteen food items to measure the dietary patterns (n 272). To test the reliability of the dietary patterns, we used the CFA to measure composite reliability (n 272) and intra-class correlation coefficients for test-retest reliability (n 113). Finally, to test the associations, we used linear regression (n 637). All factor loadings, except one, in CFA indicated acceptable correlations between foods and dietary patterns (r>0·40), and model-fit criteria were >0·90. Composite and test-retest reliability of the dietary patterns were, respectively, 0·56 and 0·34 for 'subsistence foods', 0·73 and 0·66 for 'processed foods', and 0·72 and 0·54 for 'fruits and vegetables'. In the multi-predictor analysis, the dietary patterns were significantly associated with dietary biomarkers, community location, age, sex and self-reported lifestyle. This analysis confirmed the reproducibility and reliability of the dietary patterns in the present study population. These dietary patterns can be used for future research and development of dietary interventions in this underserved population.

A meta-analysis and genome-wide association study of platelet count and mean platelet volume in african americans.

Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p<5×10(-8) of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value): 6p22 (rs12526480, LRRC16A, p = 9.1×10(-9)), 7q11 (rs13236689, CD36, p = 2.8×10(-9)), 10q21 (rs7896518, JMJD1C, p = 2.3×10(-12)), 11q13 (rs477895, BAD, p = 4.9×10(-8)), and 20q13 (rs151361, SLMO2, p = 9.4×10(-9)). Three of these loci (10q21, 11q13, and 20q13) were replicated in European Americans (N = 14,909) and one (11q13) in Hispanic Americans (N = 3,462). For MPV (N = 4,531), genetic variants in 3 regions were significant at p<5×10(-8), two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24). Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic groups. In addition, we also found one region associated with platelet aggregation that may play a potential role in atherothrombosis.

My family medical history and me: feasibility results of a cardiovascular risk reduction intervention.

OBJECTIVE: Evaluate the feasibility and acceptability of a behaviorally focused intervention designed to increase perceived cardiovascular disease (CVD) and coronary heart disease (CHD) risk in young adults with a family history (FH) of CVD/CHD. DESIGN AND SAMPLE: Single group, pre-post-test design. Fifteen, mostly female (n = 13, 86.7%), White, young adults (mean age 20.8 years) with a minimum of a high school education with a FH of CVD/CHD. MEASURES: Feasibility examined the recruitment strategy, study procedures, appropriateness and quality of the study instruments, and problems that occurred during delivery of the intervention. Acceptability examined participants' engagement in the in person sessions and at home exercises and their feedback about the intervention. INTERVENTION: Two, in person sessions provided personalized, tailored messages about 10-year and lifetime CHD risk based on risk factors, FH from a three-generation pedigree, lipid levels, blood pressure, and smoking status, and brief counseling about how to engage in a healthy lifestyle to decrease CVD/CHD risk. RESULTS: The intervention was feasible and acceptable. Participants requested more information on healthy food choices, including which foods to avoid and which exercises most improve cardiovascular health. CONCLUSIONS: Although requiring refinement, the intervention has potential public health implications and deserves further testing.

Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review.

Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, have proven efficacy in both lowering low-density-lipoprotein levels and preventing major coronary events, making them one of the most commonly prescribed drugs in the United States. Statins exhibit a class-wide side effect of muscle toxicity and weakness, which has led regulators to impose both dosage limitations and a recall. This review focuses on the best-characterized genetic factors associated with increased statin muscle concentrations, including the genes encoding cytochrome P450 enzymes (CYP2D6, CYP3A4, and CYP3A5), a mitochondrial enzyme (GATM), an influx transporter (SLCO1B1), and efflux transporters (ABCB1 and ABCG2). A systematic literature review was conducted to identify relevant research evaluating the significance of genetic variants predictive of altered statin concentrations and subsequent statin-related myopathy. Studies eligible for inclusion must have incorporated genotype information and must have associated it with some measure of myopathy, either creatine kinase levels or self-reported muscle aches and pains. After an initial review, focus was placed on seven genes that were adequately characterized to provide a substantive review: CYP2D6, CYP3A4, CYP3A5, GATM, SLCO1B1, ABCB1, and ABCG2. All statins were included in this review. Among the genetic factors evaluated, statin-related myopathy appears to be most strongly associated with variants in SLCO1B1.

All-cause, cardiovascular, and cancer mortality in western Alaska Native people: western Alaska Tribal Collaborative for Health (WATCH).

OBJECTIVES: We determined all-cause, cardiovascular disease (CVD), and cancer mortality in western Alaska Native people and examined agreement between death certificate information and adjudicated cause of deaths. METHODS: Data from 4 cohort studies were consolidated. Death certificates and medical records were reviewed and adjudicated according to standard criteria. We compared adjudicated CVD and cancer deaths with death certificates by calculating sensitivity, specificity, predictive values, and κ statistics. RESULTS: Men (n = 2116) and women (n = 2453), aged 18 to 95 years, were followed an average of 6.7 years. The major cause of death in men was trauma (25%), followed by CVD (19%) and cancer (13%). The major cause of death in women was CVD (24%), followed by cancer (19%) and trauma (8%). Stroke rates in both genders were higher than those of US Whites. Only 56% of deaths classified as CVD by death certificate were classified as CVD by standard criteria; discordance was higher among men (55%) than women (32%; κs = 0.4 and 0.7). CONCLUSIONS: We found lower rates for coronary heart disease death but high rates of stroke mortality. Death certificates overestimated CVD mortality; concordance between the 2 methods is better for cancer mortality. The results point to the importance of cohort studies in this population in providing data to assist in health care planning.

Using exploratory factor analysis of FFQ data to identify dietary patterns among Yup'ik people.

OBJECTIVE: An FFQ developed by the Center for Alaska Native Health Research for studies in Yup'ik people includes market foods and subsistence foods such as moose, seal, waterfowl and salmon that may be related to disease risk. Because the FFQ contains >100 food items, we sought to characterize dietary patterns more simply for use in ongoing pharmacogenomics studies. DESIGN: Exploratory factor analysis was used to derive a small number of 'factors' that explain a substantial amount of the variation in the Yup'ik diet. We estimated factor scores and measured associations with demographic characteristics and biomarkers. SETTING: South-west Alaska, USA. SUBJECTS: Yup'ik people (n 358) aged ≥18 years. RESULTS: We identified three factors that each accounted for ≥10 % of the common variance: the first characterized by 'processed foods' (e.g. salty snacks, sweetened cereals); the second by 'fruits and vegetables' (e.g. fresh citrus, potato salad); and the third by 'subsistence foods' (seal or walrus soup, non-oily fish). Participants from coastal communities had higher values for the 'subsistence' factor, whereas participants from inland communities had higher values for the 'fruits and vegetables' factor. A biomarker of marine intake, δ 15N, was correlated with the 'subsistence' factor, whereas a biomarker of corn- and sugarcane-based market food intake, δ 13C, was correlated with 'processed foods'. CONCLUSIONS: The exploratory factor analysis identified three factors that appeared to reflect dietary patterns among Yup'ik based on associations with participant characteristics and biomarkers. These factors will be useful for chronic disease studies in this population.