Factors associated with time to initiation of a PCSK9 inhibitor after hospital discharge for acute myocardial infarction.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) lower atherosclerotic cardiovascular disease (ASCVD) event risk. OBJECTIVE: Analyze patient characteristics associated with time to PCSK9i initiation following an acute myocardial infarction (AMI). METHODS: We analyzed characteristics of patients ≥21 years of age in the Marketscan or Medicare databases who initiated a PCSK9i 0-89 days, 90-179 days, or 180-365 days after an AMI between July 2015 and December 2018 (n=1,705). We estimated the cumulative incidence of recurrent ASCVD events before PCSK9i initiation. RESULTS: Overall, 42%, 25%, and 33% of patients who initiated a PCSK9i did so 0-89 days, 90-179 days, and 180-365 days following AMI hospital discharge, respectively. Taking ezetimibe prior to AMI hospitalization and initiating ezetimibe within 30 days after AMI hospital discharge were each associated with a higher likelihood of PCSK9i initiation in the 0-89 days versus 180-365 days post-discharge (adjusted odds ratio [OR] 1.83, 95% confidence interval [95%CI] 1.35-2.49 and 1.76, 95%CI 1.11-2.80, respectively). Statin use before and statin initiation within 30 days after AMI hospitalization were associated with a lower likelihood of PCSK9i initiation 0-89 days versus 180-365 days post-discharge (adjusted OR 0.64, 95%CI 0.49-0.84 and 0.39, 95%CI 0.28-0.54, respectively). Overall, 8.0%, 10.5%, and 12.5% of patients had an ASCVD event at 90, 180, and 365 days following AMI hospital discharge and before initiating a PCSK9i, respectively. CONCLUSION: Among patients initiating a PCSK9i after AMI, a low proportion did so within 89 days of hospital discharge. Many patients had a recurrent ASCVD event before treatment initiation.

Psychosocial correlates of apparent treatment-resistant hypertension in the Jackson Heart Study.

This corrects the article DOI: 10.1038/jhh.2016.100.

Psychosocial correlates of apparent treatment-resistant hypertension in the Jackson Heart Study.

Apparent treatment-resistant hypertension (aTRH) is associated with adverse cardiovascular outcomes. aTRH is common and disproportionately affects African Americans. The objective of this study is to explore psychosocial correlates of aTRH in a population-based cohort of African Americans with hypertension. The sample included 1392 participants in the Jackson Heart Study with treated hypertension who reported being adherent to their antihypertensive medications. aTRH was defined as uncontrolled clinic BP (⩾140/90 mm Hg) with ⩾3 classes of antihypertensive medication or treatment with ⩾4 classes of antihypertensive medication, including a diuretic. Self-reported medication adherence was defined as taking all prescribed antihypertensive medication in the 24 h before the study visit. The association of psychosocial factors (chronic stress, depressive symptoms, perceived social support and social network) with aTRH was evaluated using Poisson regression with progressive adjustment for demographic, clinical and behavioural factors. The prevalence of aTRH was 15.1% (n=210). Participants with aTRH had lower social network scores (that is, fewer sources of regular social contact) compared with participants without aTRH (P<0.01). No other psychosocial factors differed between groups. Social network was also the only psychosocial factor that was associated with aTRH prevalence in regression analyses. In age-, sex-adjusted and fully adjusted models, one additional unique source of social contact was associated with a 19% (PR=0.81; 95% confidence interval (CI): 0.68-0.94, P=0.001) and a 13% (PR=0.87; 95% CI 0.74-1.0, P=0.041) lower prevalence of aTRH, respectively. Social network was independently associated with aTRH and warrants further investigation as a potentially modifiable determinant of aTRH in African Americans.

Ambulatory blood pressure monitoring phenotypes among individuals with and without diabetes taking antihypertensive medication: the Jackson Heart Study.

Ambulatory blood pressure monitoring (ABPM) can detect phenotypes associated with increased cardiovascular disease (CVD) risk. Diabetes is associated with increased CVD risk but few data are available documenting whether blood pressure (BP) phenotypes, detected by ABPM, differ between individuals with versus without diabetes. We conducted a cross-sectional analysis of 567 participants in the Jackson Heart Study, a population-based study of African Americans, taking antihypertensive medication to evaluate the association between diabetes and ABPM phenotypes. Two clinic BP measurements were taken at baseline following a standardized protocol. ABPM was performed for 24 h following the clinic visit. ABPM phenotypes included daytime, sustained, nocturnal and isolated nocturnal hypertension, a non-dipping BP pattern, and white coat, masked and masked isolated nocturnal hypertension. Diabetes was defined as fasting glucose ⩾126 mg dl-1, haemoglobin A1c ⩾6.5% (48 mmol mol-1) or use of insulin or oral hypoglycaemic medications. Of the included participants (mean age 62.3 years, 71.8% female), 196 (34.6%) had diabetes. After multivariable adjustment, participants with diabetes were more likely to have daytime hypertension (prevalence ratio (PR): 1.32; 95% confidence interval (CI): 1.09-1.60), masked hypertension (PR: 1.46; 95% CI: 1.11-1.93) and masked isolated nocturnal hypertension (PR: 1.39; 95% CI: 1.02-1.89). Although nocturnal hypertension was more common among participants with versus without diabetes, this association was not present after adjustment for daytime systolic BP. Diabetes was not associated with the other ABPM phenotypes investigated. This study highlights the high prevalence of ABPM phenotypes among individuals with diabetes taking antihypertensive medication.

Medication adherence and visit-to-visit variability of systolic blood pressure in African Americans with chronic kidney disease in the AASK trial.

Lower adherence to antihypertensive medications may increase visit-to-visit variability of blood pressure (VVV of BP), a risk factor for cardiovascular events and death. We used data from the African American Study of Kidney Disease and Hypertension (AASK) trial to examine whether lower medication adherence is associated with higher systolic VVV of BP in African Americans with hypertensive chronic kidney disease (CKD). Determinants of VVV of BP were also explored. AASK participants (n=988) were categorized by self-report or pill count as having perfect (100%), moderately high (75-99%), moderately low (50-74%) or low (<50%) proportion of study visits with high medication adherence over a 1-year follow-up period. We used multinomial logistic regression to examine determinants of medication adherence, and multivariable-adjusted linear regression to examine the association between medication adherence and systolic VVV of BP, defined as the coefficient of variation or the average real variability (ARV). Participants with lower self-reported adherence were generally younger and had a higher prevalence of comorbid conditions. Compared with perfect adherence, moderately high, moderately low and low adherence was associated with 0.65% (±0.31%), 0.99% (±0.31%) and 1.29% (±0.32%) higher systolic VVV of BP (defined as the coefficient of variation) in fully adjusted models. Results were qualitatively similar when using ARV or when using pill counts as the measure of adherence. Lower medication adherence is associated with higher systolic VVV of BP in African Americans with hypertensive CKD; efforts to improve medication adherence in this population may reduce systolic VVV of BP.

Visit-to-visit systolic blood pressure variability and outcomes in hemodialysis.

Visit-to-visit blood pressure variability (VTV-BPV) is an independent risk factor for cardiovascular events and death in the general population. We sought to determine the association of VTV-BPV with outcomes in patients on hemodialysis, using data from a National Institutes of Health-sponsored randomized trial (the HEMO study). We used the coefficient of variation (CV) and the average real variability in systolic blood pressure (SBP) as metrics of VTV-BPV. In all, 1844 out of 1846 randomized subjects had at least three visits with SBP measurements and were included in the analysis. Median follow-up was 2.5 years (interquartile range 1.3-4.3 years), during which time there were 869 deaths from any cause and 408 (adjudicated) cardiovascular deaths. The mean pre-dialysis SBP CV was 9.9 ± 4.6%. In unadjusted models, we found a 31% higher risk of death from any cause per 10% increase in VTV-BPV. This association was attenuated after multivariable adjustment but remained statistically significant. Similarly, we found a 28% higher risk of cardiovascular death per 10% increase in VTV-BPV, which was attenuated and no longer statistically significant in fully adjusted models. The associations among VTV-BPV, death and cardiovascular death were modified by baseline SBP. In a diverse, well-dialyzed cohort of patients on maintenance hemodialysis, VTV-BPV, assessed using metrics of variability in pre-dialysis SBP, was associated with a higher risk of all-cause mortality and a trend toward higher risk of cardiovascular mortality, particularly in patients with a lower baseline SBP.

Primary non-adherence to bisphosphonates in an integrated healthcare setting.

UNLABELLED: We estimated primary non-adherence to oral bisphosphonate medication and examined the factors associated with primary non-adherence. Nearly 30% of women did not pick up their new bisphosphonate within 60 days. Identifying barriers and developing interventions that address patients' needs and concerns at the time a new medication is prescribed are warranted. INTRODUCTION: To estimate primary non-adherence to oral bisphosphonate medications using electronic medical record data in a large, integrated healthcare delivery system and to describe patient and prescribing provider factors associated with primary non-adherence. METHODS: Women aged 55 years and older enrolled in Kaiser Permanente Southern California (KPSC) with a new prescription for oral bisphosphonates between December 1, 2009 and March 31, 2011 were identified. Primary non-adherence was defined as failure to pick up the new prescription within 60 days of the order date. Multivariable logistic regression models were used to investigate patient factors (demographics, healthcare utilization, and health conditions) and prescribing provider characteristics (demographics, years in practice, and specialty) associated with primary non-adherence. RESULTS: We identified 8,454 eligible women with a new bisphosphonate order. Among these women, 2,497 (29.5%) did not pick up their bisphosphonate prescription within 60 days of the order date. In multivariable analyses, older age and emergency department utilization were associated with increased odds of primary non-adherence while prescription medication use and hospitalizations were associated with lower odds of primary non-adherence. Prescribing providers practicing 10 or more years had lower odds of primary non-adherent patients compared with providers practicing less than 10 years. Internal medicine and rheumatology providers had lower odds of primary non-adherent patients than primary care providers. CONCLUSION: This study found that nearly one in three women failed to pick up their new bisphosphonate prescription within 60 days. Identifying barriers and developing interventions aimed at reducing the number of primary non-adherent patients to bisphosphonate prescriptions are warranted.

Relationships between metrics of visit-to-visit variability of blood pressure.

This paper examines relationships between metrics of visit-to-visit variability (VVV) of blood pressure (BP) to determine which metrics should be calculated in studies of the association of VVV with health outcomes. We examined correlation and agreement between quintiles for standard deviation (s.d.), standard deviation independent of the mean (SDIM), coefficient of variation (CV), successive variation (SV), average real variability (ARV), range, maximum, peak size and trough size of systolic BP in the Trial of Preventing Hypertension placebo arm (n=288). The average age of participants was 48 years. Mean systolic BP was 133.5 mm Hg. VVV metrics were all significantly correlated (P<0.001). Correlations between s.d., SDIM, CV and range and between ARV and SV were ≥0.90. Kappa statistics between quintiles of SD, SDIM, CV and range and between ARV and SV were ≥0.80. In studies of the relationship of VVV with health outcomes, we recommend reporting results for one of the metrics of overall variability (s.d., SDIM, CV), one of the metrics of variability between consecutive visits (SV, ARV), and one or more of the metrics of extreme values at a single visit (maximum, peak size, trough size).

The association of biomarkers of iron status with mortality in US adults.

BACKGROUND AND AIMS: Elevated iron biomarkers are associated with diabetes and other cardiometabolic abnormalities in the general population. It is unclear whether they are associated with an increased risk of all-cause or cause-specific mortality. The purpose of the current analysis was to evaluate the association of ferritin and transferrin saturation levels with all-cause, cardiovascular, and cancer mortality in the general US adult population. METHODS AND RESULTS: A prospective cohort study was conducted with 12,258 adults participating in the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative sample of the US population. Study participants were recruited in 1988-1994 and followed through December 31, 2006 for all-cause, cardiovascular disease, and cancer mortality. The multivariable-adjusted hazard ratios (95% confidence interval) for all-cause mortality comparing the fourth versus the second quartiles of ferritin and transferrin saturation were 1.09 (0.82-1.44; p-trend across quartiles = 0.92) and 1.08 (0.82-1.43; p-trend across quartiles = 0.62), respectively, for men, 1.43 (0.63-3.23; p-trend across quartiles = 0.31) and 1.48 (0.70-3.11; p-trend across quartiles = 0.60), respectively, for premenopausal women, and 1.03 (0.79-1.34; p-trend across quartiles = 0.95) and 1.17 (0.92-1.49; p-trend across quartiles = 0.63), respectively, for postmenopausal women. Quartile of ferritin and transferrin saturation also showed no association between biomarkers of iron status and mortality. CONCLUSIONS: In a large nationally representative sample of US adults, within the spectrum of normal iron metabolism, ferritin and transferrin saturation were not associated with risk of mortality among people who were not taking iron supplements and did not have a baseline history of cardiovascular disease or cancer.

Association of pulse wave velocity with vascular and valvular calcification in hemodialysis patients.

The recent Kidney Disease: Improving Quality Outcomes (KDIGO) recommendations called for an investigation of the relationship between various radiological methods to assess cardiovascular calcification and measures of arterial stiffness. Accordingly, in 131 adult maintenance hemodialysis patients, we investigated the association of aortic pulse wave velocity (PWV) with calcification of cardiac valves on echocardiography, coronary artery, and thoracic aorta calcium on computed tomography and a calcification score of the abdominal aorta obtained on a plain abdominal X-ray. All tests were performed within a week. Mean PWV increased as the severity of coronary artery, thoracic, and abdominal aorta calcium scores increased (each P<0.05). No trend was present for number of valves with calcification. After multivariable adjustment, abdominal aorta X-ray calcium scores remained associated with PWV (P=0.004), whereas the association of PWV with thoracic aorta and coronary artery calcium scores became marginal (P=0.308 and P=0.083, respectively). No association was found between number of calcified valves and PWV. This study demonstrates a strong association between abdominal aorta calcification on plain X-ray and PWV and a borderline association with thoracic aorta and coronary artery calcification. Sudden death and congestive heart failure, two frequent causes of death in hemodialysis, are likely caused by increased arterial stiffness that can be closely predicted by the presence of aortic calcification on plain X-rays.

Correlation of simple imaging tests and coronary artery calcium measured by computed tomography in hemodialysis patients.

Vascular calcification is associated with an adverse prognosis in end-stage renal disease. It can be accurately quantitated with computed tomography but simple in-office techniques may provide equally useful information. Accordingly we compared the results obtained with simple non-invasive techniques with those obtained using electron beam tomography (EBT) for coronary artery calcium scoring (CACS) in 140 prevalent hemodialysis patients. All patients underwent EBT imaging, a lateral X-ray of the lumbar abdominal aorta, an echocardiogram, and measurement of pulse pressure (PP). Calcification of the abdominal aorta was semiquantitatively estimated with a score (Xr-score) of 0-24 divided into tertiles, echocardiograms were graded as 0-2 for absence or presence of calcification of the mitral and aortic valve and PP was divided in quartiles. The CACS was elevated (mean 910+/-1657, median 220). The sensitivity and specificity for CACS > or = 100 was 53 and 70%, for calcification of either valve and 67 and 91%, respectively, for Xr-score > or = 7. The area under the curve for CACS > or = 100 associated with valve calcification and Xr-score was 0.62 and 0.78, respectively. The likelihood ratio (95% confidence interval) of CACS > or = 100 was 1.79 (1.09, 2.96) for calcification of either valve and 7.50 (2.89, 19.5) for participants with an Xr-score > or = 7. In contrast, no association was present between PP and CACS. In conclusion, simple measures of cardiovascular calcification showed a very good correlation with more sophisticated measurements obtained with EBT. These methodologies may prove very useful for in-office imaging to guide further therapeutic choices in hemodialysis patients.

Prevalence, awareness, treatment and control of hypertension in North America, North Africa and Asia.

Results from national surveys of prevalence, awareness, treatment and control provide the most meaningful basis for assessing the burden of hypertension in the community. National surveys conducted in a variety of countries in North America, Europe, Australia, Asia and Africa have identified a strikingly similar relationship between age and blood pressure (BP), with a progressive and steep increase in systolic BP throughout adult life and a less steep increase in diastolic BP from adolescence until the fifth or sixth decade. In most countries surveyed, there was a high prevalence of hypertension. Approximately, one quarter of all adults in the United States and Egypt had hypertension (systolic BP>/=140 mmHg or diastolic BP>/=90 mmHg or use of antihypertensive medication) in national surveys conducted in 1988-1991 and 1991-1993, respectively. The corresponding percentage was somewhat lower (14.4%) for adults surveyed in China during 1991, but temporal trends indicate that the prevalence of hypertension is increasing rapidly in that country. In the 1988-1991 national survey, more than 25% of US adults were unaware of their diagnosis, only 55% were being treated with antihypertensive medication and only 29% were on antihypertensive medication with a systolic/diastolic BP >140/90 mmHg. The situation was much worse in Egypt and China, with only 8% and <5% of adults with hypertension, respectively, being treated with antihypertensive medication and having a systolic/diastolic BP <140/90 mmHg. These survey results underscore the fact that hypertension is highly prevalent, poorly treated and controlled, and an escalating health challenge in economically developing countries.

Predictors of participation and attendance in a new asthma patient self-management education program.

BACKGROUND: Low participation limits the effectiveness of patient education interventions. In this study, the characteristics of patients who agreed to participate in a clinical trial of disease self-management education for asthma were compared to the characteristics of those who declined, and among the former group patients who actually attended were compared to those who did not. METHODS: The education program, implemented at the Geneva University Hospitals between 1996 and 1998, consisted of three interactive sessions spread over 3 weeks. Only 131 of 253 eligible patients (52%) agreed to participate in the trial, and only 83 patients (63%) attended two to three educational sessions. All eligible patients filled out baseline questionnaires and were interviewed by a trained physiotherapist. RESULTS: Lower confidence in the patient's own current treatment regimen and a more severe baseline asthma attack were independently associated with participation in the trial. Among those who agreed to participate in the study, a university education, longer asthma duration, older age, and a higher level of asthma management knowledge were associated with higher attendance. Quality-of-life scores were not associated with higher course attendance. Among all eligible participants, persons with lower knowledge of asthma management (which was assessed by what to do during an asthma attack and knowledge of the correct use of a peak expiratory flowmeter and inhalers) were less likely to enroll in the trial and to attend the educational training sessions. CONCLUSIONS: Strategies need to be developed to motivate patients with lower disease self-management knowledge to participate in asthma education programs.

Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study.

BACKGROUND: Animal and in vitro data suggest that dyslipidemia plays an important role in the initiation and progression of chronic renal disease, but few prospective studies have been conducted in humans. METHODS: We studied the relationship of plasma lipids to a rise in serum creatinine of 0.4 mg/dL or greater in 12,728 Atherosclerosis Risk in Communities (ARIC) participants with baseline serum creatinine that was less than 2.0 mg/dL in men and less than 1.8 mg/dL in women. RESULTS: During a mean follow-up of 2.9 years, 191 persons had a rise in creatinine of 0.4 mg/dL or greater, yielding an incidence rate of 5.1 per 1000 person years. Individuals with higher triglycerides and lower high-density lipoprotein (HDL) and HDL-2 cholesterol at baseline were at increased risk for a rise in creatinine after adjustment for race, gender, baseline age, diabetes, serum creatinine, systolic blood pressure, and antihypertensive medication use (all P trends

Comparison of the psychometric properties of the Asthma Quality of life Questionnaire (AQLQ) among 115 asthmatic adults assessed during acute hospitalization and as outpatients.

Health status instruments designed for outpatient settings may not perform as intended when applied to hospitalized patients. In this study, we assessed similarities and differences between the psychometric properties of the Asthma Quality of Life Questionnaire (AQLQ) in-hospital and during an outpatient visit 6 months later, in a cohort of 115 patients. No ceiling or floor effects were present at either visit. At both visits, all scales except for 'environment' had internal consistency coefficients > 0.7 (ENVIRONMENT: 0.69--hospitalization; 0.68--outpatient). On both occasions, over 75% of item-scale correlation scores were > 0.4 and over 80% correlated to a greater degree with their own scale total than with the other three scales. However, at both visits, the AQLQ standard activity items had a higher correlation with the environment scale than with respondent-defined activity items; this finding re-occurred during exploratory factor analysis. Finally, the AQLQ performed similarly in construct validity tests in the two settings. In conclusion, this study provides evidence that the AQLQ has similar psychometric properties during an acute hospitalization and subsequently in an outpatient setting.