Immediate post-exercise blood pressure and arterial compliance in middle-aged and older normotensive females: A cross-sectional study.

This study examined whether immediate post-exercise systolic blood pressure (SBP) is associated with arterial compliance in middle-aged and older normotensive females. A total of 548 normotensive, non-frail females aged 55 years and older with no previous history of cardiovascular disease (CVD) participated in this cross-sectional study. Large and small arterial compliance were assessed by pulse wave analysis. Reduced arterial compliance was defined based on age and sex cutoffs. SBP was measured at rest and immediately following a 3-min moderate step-test. CVD risk factors were also assessed (e.g. resting systolic and diastolic BP, fasting glucose, triglycerides, cholesterol, body mass index). A total of 15.1% and 44.0% of the participants showed reduced large and small artery compliance, respectively. Immediate post-exercise SBP was associated with reduced large (OR 1.02 per 1 mmHg increase in post-exercise SBP, 95%CI 1.01-1.04; p = 0.010) and small (OR 1.02 per 1 mmHg increase in post-exercise SBP, 95%CI 1.00-1.03; p = 0.008) arterial compliance. Participants with highest immediate post-exercise SBP (quartile 4; i.e. ≥ 165 mmHg) showed increased odds ratios for reduced large (2.67, 95%CI 1.03-6.94; p = 0.043) and small (2.27, 95%CI 1.22-4.21; p = 0.010) arterial compliance compared to those with the lowest immediate post-exercise SBP (quartile 1; i.e. ≤ 140 mmHg), independent of other established CVD risk factors. Immediate post-exercise SBP following a brief moderate step-test seems to be able to discriminate reduced arterial compliance in middle-aged and older normotensive females.

Practice advisory update summary: Patent foramen ovale and secondary stroke prevention: Report of the Guideline Subcommittee of the American Academy of Neurology.

OBJECTIVE: To update the 2016 American Academy of Neurology (AAN) practice advisory for patients with stroke and patent foramen ovale (PFO). METHODS: The guideline panel followed the AAN 2017 guideline development process to systematically review studies published through December 2017 and formulate recommendations. MAJOR RECOMMENDATIONS: In patients being considered for PFO closure, clinicians should ensure that an appropriately thorough evaluation has been performed to rule out alternative mechanisms of stroke (level B). In patients with a higher risk alternative mechanism of stroke identified, clinicians should not routinely recommend PFO closure (level B). Clinicians should counsel patients that having a PFO is common; that it occurs in about 1 in 4 adults in the general population; that it is difficult to determine with certainty whether their PFO caused their stroke; and that PFO closure probably reduces recurrent stroke risk in select patients (level B). In patients younger than 60 years with a PFO and embolic-appearing infarct and no other mechanism of stroke identified, clinicians may recommend closure following a discussion of potential benefits (absolute recurrent stroke risk reduction of 3.4% at 5 years) and risks (periprocedural complication rate of 3.9% and increased absolute rate of non-periprocedural atrial fibrillation of 0.33% per year) (level C). In patients who opt to receive medical therapy alone without PFO closure, clinicians may recommend an antiplatelet medication such as aspirin or anticoagulation (level C).

Acute Effect of High-Intensity Interval Versus Moderate-Intensity Continuous Exercise on Blood Pressure and Arterial Compliance in Middle-Aged and Older Hypertensive Women With Increased Arterial Stiffness.

Costa, EC, Kent, DE, Boreskie, KF, Hay, JL, Kehler, DS, Edye-Mazowita, A, Nugent, K, Papadopoulos, J, Stammers, AN, Oldfield, C, Arora, RC, Browne, RAV, and Duhamel, TA. Acute effect of high-intensity interval versus moderate-intensity continuous exercise on blood pressure and arterial compliance in middle-aged and older hypertensive women with increased arterial stiffness. J Strength Cond Res 34(5): 1307-1316, 2020-Hypertension and arterial stiffness are common in middle-aged and older women. This study compared the acute effect of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on blood pressure (BP) and arterial compliance in middle-aged and older hypertensive women with increased arterial stiffness. Nineteen women (67.6 ± 4.7 years) participated in this randomized controlled crossover trial. Subjects completed a control, MICE (30 minutes at 50-55% of heart rate reserve [HRR]), and HIIE (10 × 1 minute at 80-85% of HRR, 2 minutes at 40-45% of HRR) session in random order. Blood pressure and large and small arterial compliance (radial artery pulse wave analysis) were measured at baseline and 30, 60, 90, and 120 minutes after sessions. A p < 0.05 was considered statistically significant. Systolic BP was reduced in ∼10 mm Hg after MICE at 30 minutes and after HIIE at all time points (30, 60, 90, and 120 minutes) after exercise compared with the control session (p < 0.05). Only HIIE showed lower systolic BP levels at 60, 90, and 120 minutes after exercise compared with the control session (∼10 mm Hg; p < 0.05). No changes were observed in diastolic BP, or in large and small arterial compliance (p > 0.05). High-intensity interval exercise elicited a longer systolic postexercise hypotension than MICE compared with the control condition, despite the absence of acute modifications in large and small arterial compliance.

Population-Based Validation of a Clinical Prediction Model for Congenital Diaphragmatic Hernias.

OBJECTIVE: To examine the external validity of a well-known congenital diaphragmatic hernia (CDH) clinical prediction model using a population-based cohort. STUDY DESIGN: Newborns with CDH born in California between 2007 and 2012 were extracted from the Vital Statistics and Patient Discharge Data Linked Files. The total CDH risk score was calculated according to the Congenital Diaphragmatic Hernia Study Group (CDHSG) model using 5 independent predictors: birth weight, 5-minute Apgar, pulmonary hypertension, major cardiac defects, and chromosomal anomalies. CDHSG model performance on our cohort was validated for discrimination and calibration. RESULTS: A total of 705 newborns with CDH were extracted from 3 213 822 live births. Newborns with CDH were delivered in 150 different hospitals, whereas only 28 hospitals performed CDH repairs (1-85 repairs per hospital). The observed mortality for low-, intermediate-, and high-risk groups were 7.7%, 34.3%, and 54.7%, and predicted mortality for these groups were 4.0%, 23.2%, and 58.5%. The CDHSG model performed well within our cohort with a c-statistic of 0.741 and good calibration. CONCLUSIONS: We successfully validated the CDHSG prediction model using an external population-based cohort of newborns with CDH in California. This cohort may be used to investigate hospital volume-outcome relationships and guide policy development.

Detecting mood disorder in resource-limited primary care settings: comparison of a self-administered screening tool to general practitioner assessment.

OBJECTIVES: Although efficacious treatments for mood disorders are available in primary care, under-diagnosis is associated with under-treatment and poorer outcomes. This study compares the accuracy of self-administered screening tests with routine general practitioner (GP) assessment for detection of current mood disorder. METHODS: 197 consecutive patients attending primary care centres in Santiago, Chile enrolled in this cross-sectional study, filling out the Patients Health Questionnaire-9 (PHQ-9) for depression and the Mood Disorder Questionnaire (MDQ) for bipolar disorder, after routine GP assessment. Diagnostic accuracy of these self-administered tools was compared with GP assessment, with gold standard diagnosis established by a structured diagnostic interview with trained clinicians (SCID-I). RESULTS: The sample was 75% female, with a mean age of 48.5 (SD 16.8); 37% had a current mood disorder (positive SCID-I result for depression or bipolar disorder). Sensitivity of the screening instruments (SI) was substantially higher than GP assessment (SI: 0.8, [95% CI 0.71, 0.81], versus GP: 0.2, [95% CI 0.12, 0.25]: p-value < 0.0001), without sacrifice in specificity (SI: 0.9, [95% CI 0.86, 0.96], versus GP: 0.9, [95% CI 0.88, 0.97]: p-value = 0.7). This led to improvement in both positive predictive value (SI: 0.8, [95% CI 0.82, 0.90], versus GP: 0.6, [95% CI 0.50, 0.64]: p-value < 0.001) and negative predictive value (SI: 0.9, [95% CI 0.78, 0.91] versus GP: 0.7, [95% CI 0.56, 0.72]: p-value < 0.01). CONCLUSION: Self-administered screening tools are more accurate than GP assessment in detecting current mood disorder in low-income primary care. Such screening tests may improve detection of current mood disorder if implemented in primary care settings.

Association of common variants, not rare mutations, in IRF6 with nonsyndromic clefts in a Honduran population.

OBJECTIVES/HYPOTHESIS: Cleft lip with or without cleft palate (CL/P) is a common birth defect throughout the world. Linkage studies have shown interferon regulatory factor 6 (IRF6) to be associated with CL/P in multiple populations, including one in Honduras. It is unknown, however, whether rare sporadic mutations or common variants are the cause of this association, and reports exist supporting both hypotheses. Thus, it is important to determine the cause for this association in a Honduran population. STUDY DESIGN: Case-control and family-based association studies. METHODS: Families with two or more members affected by CL/P were identified. We collected DNA from affected and unaffected family members (608 total), and from 100 gender-matched controls from Honduras. We sequenced the exons of IRF6 for mutations in probands and controls. All patients were genotyped for single nucleotide polymorphisms (SNPs) rs642961 and rs2235371, which are proposed to have potential biological significance to IRF6 expression and function. RESULTS: We found no mutations in IRF6 in our CL/P probands. We found a risk association with the G allele of rs2235371 in both case-control (P = .01) and family-based association (P = .01) studies. We found no association with either allele of rs642961. CONCLUSIONS: This study suggests that common variants, rather than rare mutations, are the cause for association between IRF6 and nonsyndromic CL/P. rs2235371, but not rs642961, shows association with CL/P, suggesting a functional role for this polymorphism in our Honduran population. rs642961 has been previously reported to have an effect in other populations, suggesting that different populations may be affected by different polymorphisms.

Novel IRF6 mutations in Honduran Van der Woude syndrome patients.

Van der Woude syndrome (VWS) is an autosomal dominant inherited disease characterized by lower lip pits, cleft lip and/or cleft palate. Missense, nonsense and frameshift mutations in IRF6 have been revealed to be responsible for VWS in European, Asian, North American and Brazilian populations. However, the mutations responsible for VWS have not been studied in Central American populations. Here, we investigated the role of IRF6 in patients with VWS in a previously unstudied Honduran population. IRF6 mutations were identified in four out of five VWS families examined, which strongly suggests that mutations in IRF6 are responsible for VWS in this population. We reported three novel mutations and one previously described mutation. In the first family, a mother and daughter both exhibited a p.N88I mutation in the DNA-binding region of IRF6 that was not present in unaffected family members. In the second, we found a unique p.K101QfsX15 mutation in the affected patient, leading to a frameshift and early stop codon. In the third, we identified a p.Q208X mutation occurring in exon 6. In the fourth, we found a nonsense mutation in exon 9 (p.R412X), previously described in Brazilian and Northern European populations. In the fifth, we did not identify any unique exonic missense, nonsense or frameshift mutations. This study reports the first cases of IRF6 mutations in VWS patients in a Central American population, further confirming that the causal link between IRF6 and VWS is consistent across multiple populations.

The association between interferon regulatory factor 6 (IRF6) and nonsyndromic cleft lip with or without cleft palate in a Honduran population.

OBJECTIVES/HYPOTHESIS: Interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome (VWS), is a candidate gene for nonsyndromic cleft lip with or without cleft palate (NSCLP) because a number of studies have supported an association between NSCLP and single nucleotide polymorphisms (SNPs) in IRF6 in several populations. This project investigated the contribution of IRF6 to NSCLP in the Honduran population, a previously unstudied group with a high prevalence of NSCLP. STUDY DESIGN: Family-based joint linkage and association study. METHODS: A set of five SNPs in and around IRF6 previously reported to be associated with NSCLP were tested for association with NSCLP in 276 affected and unaffected Honduran individuals from 59 families with at least two members affected by clefting and at least one member with confirmed NSCLP. RESULTS: We observed support of linkage for three SNPs-rs1856161, rs2235371, and rs2235377-under a dominant model (log of odds [LODs] = 1.97, 1.56, 1.73, respectively). Subsequent single-point, haplotype, and joint linkage and association analyses continued to support the association with NSCLP (P < or = .05) at these three SNPs. When analysis was restricted to NSCLP cases, excluding cleft palate only cases, support for association strengthened. CONCLUSIONS: This is the first study to demonstrate that three candidate SNPs within IRF6 are significantly associated with NSCLP in the Honduran population, providing the first genetic clue to NSCLP observed in the Honduran population and confirming findings from populations in other parts of the world. Further studies are needed to identify the putative variant(s).