Incidence of Atherosclerotic Cardiovascular Disease in Young Adults at Low Short-Term But High Long-Term Risk.

BACKGROUND: Young adults may have high long-term atherosclerotic cardiovascular disease (ASCVD) risk despite low short-term risk. OBJECTIVES: In this study, we sought to compare the performance of short-term and long-term ASCVD risk prediction tools in young adults and evaluate ASCVD incidence associated with predicted short-term and long-term risk. METHODS: We included adults aged 18 to 39 years, from 2008 to 2009 in a U.S. integrated health care system, and followed them through 2019. We calculated 10-year and 30-year ASCVD predicted risk and assessed ASCVD incidence. RESULTS: Among 414,260 young adults, 813 had an incident ASCVD event during a median of 4 years (maximum 11 years). Compared with 10-year predicted risk, 30-year predicted risk improved reclassification (net reclassification index: 16%) despite having similar discrimination (Harrell's C: 0.749 vs 0.726). Overall, 1.0% and 2.2% of young adults were categorized as having elevated 10-year (≥7.5%) and elevated 30-year (≥20%) predicted risk, respectively, and 1.6% as having low 10-year (<7.5%) but elevated 30-year predicted risk. The ASCVD incidence rate per 1,000 person-years was 2.60 (95% CI: 1.92-3.52) for those with elevated 10-year predicted risk, 1.87 (95% CI: 1.42-2.46) for those with low 10-year but elevated 30-year predicted risk, and 0.32 (95% CI: 0.30-0.35) for those with low 10-year and 30-year predicted risk. The age- and sex-adjusted incidence rate ratio was 3.04 (95% CI: 2.25-4.10) comparing those with low 10-year but elevated 30-year predicted risk and those with low 10-year and 30-year predicted risk. CONCLUSIONS: Long-term ASCVD risk prediction tools further discriminate a subgroup of young adults with elevated observed risk despite low estimated short-term risk.

Comparison of Blood Pressure Measurements from Clinical Practice and a Research Study At Kaiser Permanente Southern California.

BACKGROUND: Accurate blood pressure (BP) measurement is essential to identify and manage hypertension. Prior studies have reported a difference between BP measured in routine patient care and in research studies. We aimed to investigate the agreement between BP measured in routine care and research-grade BP in Kaiser Permanente Southern California, a large, integrated healthcare system with initiatives to standardize BP measurements during routine patient care visits. METHODS: We included adults ≥65 years old with hypertension, taking antihypertensive medication, and participating in the Ambulatory Blood Pressure in Older Adults (AMBROSIA) study in 2019-2021. Clinic BP from routine care visits was extracted from the electronic health record. Research-grade BP was obtained by trained AMBROSIA study staff via an automatic oscillometric device. The mean difference between routine care and research-grade BP, limits of agreement, and correlation were assessed. RESULTS: We included 309 participants (mean age 75 years; 54% female; 49% non-Hispanic white). Compared with measurements from routine care, mean research-grade systolic BP (SBP) was 0.1 mm Hg higher (95% CI: -1.5 to 1.8) and diastolic BP (DBP) was 0.4 mm Hg lower (95% CI: -1.6 to 0.7). Limits of agreement were -29 to 30 mm Hg for SBP and -21 to 20 mm Hg for DBP. The intraclass correlation coefficient was 0.42 (95% CI: 0.33 to 0.51) for SBP and 0.43 (95% CI: 0.34 to 0.52) for DBP. CONCLUSIONS: High within-person variation and moderate correlation were present between BP measured in routine care and following a research protocol suggesting the importance of standardized measurements.

Blood Pressure Control Among Black and White Adults Following a Quality Improvement Program in a Large Integrated Health System.

Importance: A higher percentage of non-Hispanic Black (hereinafter, Black) adults vs non-Hispanic White (hereinafter, White) adults with hypertension have uncontrolled blood pressure (BP) contributing to racial and ethnic disparities in cardiovascular disease. In 2010, Kaiser Permanente Southern California began implementing quality improvement (QI) strategies aimed at reducing this disparity. Objective: To examine the change in BP control between Black and White patients before and after the implementation of a QI program. Design, Setting, and Participants: A QI quasi-experimental, difference-in-difference analysis was conducted of Kaiser Permanente Southern California patients 18 years or older included in the population care management hypertension registry. The study was conducted from December 31, 2008, to December 31, 2019. Data analysis was performed from November 20, 2020, to November 7, 2022. Interventions: Quality improvement program implementation began in 2010. Main Outcomes and Measures: Blood pressure control (systolic BP <140 mm Hg and diastolic BP <90 mm Hg) was assessed using the last outpatient BP measurement in each calendar year. Changes in BP control between Black and White patients from before (2008-2009) to after (2016-2019) implementation of the QI program were examined using a difference-in-difference analysis. Blood pressure control disparities from 2008 through 2019 by age, sex, race and ethnicity, and factors associated with BP control were examined. Results: The number of patients with hypertension increased from 624 094 in 2008 (mean [SD] age, 61.8 [13.5] years; 330 551 [53.0%] female patients; 89 407 [14.3%] Black and 284 116 [45.5%] White patients) to 855 257 in 2019 (mean [SD] age, 64.5 [13.6] years; 444 422 [52.0%] female patients; 107 054 [12.5%] Black and 331 932 [38.8%] White patients). Blood pressure control increased an absolute 4.6% (95% CI, 4.3%-4.8%) among Black patients and 2.1% (95% CI, 2.0%-2.2%) among White patients from before to after the QI program implementation (difference-in-difference: 2.5%; 95% CI, 2.2%-2.8%). The largest reduction in BP control disparity between Black and White female patients was for those aged 50 to 64 years (difference-in-difference: 3.8%; 95% CI, 3.2%-4.4%) and for those aged 18 to 49 years between Black and White male patients (difference-in-difference: 4.2%; 95% CI, 3.0%-5.5%). The proportion of BP control among Black male patients aged 18 to 49 years was the lowest throughout 2008-2019 compared with male and female patients in other age and racial and ethnic groups. In 2019, uncontrolled BP was more common among Black vs White patients (prevalence ratio: 1.13; 95% CI, 1.12-1.14). Conclusions and Relevance: This QI program noted that disparities in BP control between Black and White patients were decreased but not eliminated following implementation of QI strategies aimed at reducing disparities in BP control. These findings suggest that more focused interventions may be needed to increase BP control among Black individuals.

Executive summary of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease for patients not receiving dialysis represents an update to the KDIGO 2012 guideline on this topic. Development of this guideline update followed a rigorous process of evidence review and appraisal. Guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence. The strength of recommendations is based on the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. The scope includes topics covered in the original guideline, such as optimal blood pressure targets, lifestyle interventions, antihypertensive medications, and specific management in kidney transplant recipients and children. Some aspects of general and cardiovascular health, such as lipid and smoking management, are excluded. This guideline also introduces a chapter dedicated to proper blood pressure measurement since all large randomized trials targeting blood pressure with pivotal outcomes used standardized preparation and measurement protocols adhered to by patients and clinicians. Based on previous and new evidence, in particular the Systolic Blood Pressure Intervention Trial (SPRINT) results, we propose a systolic blood pressure target of less than 120 mm Hg using standardized office reading for most people with chronic kidney disease (CKD) not receiving dialysis, the exception being children and kidney transplant recipients. The goal of this guideline is to provide clinicians and patients a useful resource with actionable recommendations supplemented with practice points. The burden of the recommendations on patients and resources, public policy implications, and limitations of the evidence are taken into consideration. Lastly, knowledge gaps and recommendations for future research are provided.

Executive summary of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease for patients not receiving dialysis represents an update to the KDIGO 2012 guideline on this topic. Development of this guideline update followed a rigorous process of evidence review and appraisal. Guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence. The strength of recommendations is based on the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. The scope includes topics covered in the original guideline, such as optimal blood pressure targets, lifestyle interventions, antihypertensive medications, and specific management in kidney transplant recipients and children. Some aspects of general and cardiovascular health, such as lipid and smoking management, are excluded. This guideline also introduces a chapter dedicated to proper blood pressure measurement since all large randomized trials targeting blood pressure with pivotal outcomes used standardized preparation and measurement protocols adhered to by patients and clinicians. Based on previous and new evidence, in particular the Systolic Blood Pressure Intervention Trial (SPRINT) results, we propose a systolic blood pressure target of less than 120 mm Hg using standardized office reading for most people with chronic kidney disease (CKD) not receiving dialysis, the exception being children and kidney transplant recipients. The goal of this guideline is to provide clinicians and patients a useful resource with actionable recommendations supplemented with practice points. The burden of the recommendations on patients and resources, public policy implications, and limitations of the evidence are taken into consideration. Lastly, knowledge gaps and recommendations for future research are provided.

Treatment Patterns and Blood Pressure Control With Initiation of Combination Versus Monotherapy Antihypertensive Regimens.

Many patients with hypertension require 2 or more drug classes to achieve their blood pressure (BP) goal. We compared antihypertensive medication treatment patterns and BP control between patients who initiated combination therapy versus monotherapy. We identified adults with hypertension enrolled in a US integrated healthcare system who initiated antihypertensive medication between 2008 and 2014. Patient demographics, clinical characteristics, antihypertensive medication, and BP were extracted from electronic health records. Antihypertensive medication patterns and multivariable adjusted prevalence ratios (PRs) of achieving the 2017 American College of Cardiology/American Heart Association guideline-recommended BP <130/80 mm Hg were evaluated for 2 years following treatment initiation. Of 135 971 patients, 43% initiated antihypertensive combination therapy (35% ACE [angiotensin converting enzyme] inhibitor (ACEI)-thiazide diuretics; 8% with other combinations) and 57% initiated monotherapy (22% ACEIs; 16% thiazide diuretics; 11% ß blockers; 8% calcium channel blockers). After multivariable adjustment including premedication BP levels, patients who initiated ACEI-thiazide diuretic combination therapy were more likely to achieve BP <130/80 mm Hg compared with their counterparts who initiated monotherapy with ACEI (PR, 1.10 [95% CI, 1.08-1.12]), thiazide diuretic (PR, 1.21 [95% CI, 1.18-1.24]), ß blocker (PR, 1.17 [95% CI, 1.14-1.20]), or calcium channel blocker (PR, 1.25 [95% CI, 1.22-1.29]). Compared with initiating monotherapy, patients initiating ACEI-thiazide diuretic combination therapy were more likely to achieve BP goals.

Recurrent Atherosclerotic Cardiovascular Event Rates Differ Among Patients Meeting the Very High Risk Definition According to Age, Sex, Race/Ethnicity, and Socioeconomic Status.

Background The risk for atherosclerotic cardiovascular disease (ASCVD) events may differ by sociodemographic factors among patients meeting the definition of very high risk according to the 2018 American Heart Association/American College of Cardiology cholesterol guideline, leading to treatment disparities. We estimated the risk for recurrent ASCVD events among adults meeting the definition of very high risk by age, sex, race/ethnicity, and socioeconomic status in a US integrated healthcare system. Methods and Results The study cohort included Kaiser Permanente Southern California members aged ≥21 years with a history of clinical ASCVD on September 30, 2009. Very high risk for recurrent ASCVD was defined by a history of ≥2 major ASCVD events or a history of 1 major event along with ≥2 high-risk conditions. Patients were followed through 2015 for a first recurrent ASCVD event. Of 77 101 patients with ASCVD, 50.8% met the definition for very high risk. Among patients meeting the definition of very high risk, recurrent ASCVD rates were higher in older (>75 years) versus younger patients (21-40 years) (sex-adjusted hazard ratio [HR] [95% CI] 1.85; 1.23-2.79), non-Hispanic Black patients versus non-Hispanic White patients (age-, sex-adjusted HR, 1.32; 1.23-1.41), those who lived in neighborhoods with lower (<$35k) versus higher annual household income (≥$80k) (HR, 1.20; 1.11-1.30), or with lower (≥31.2%) versus higher education levels (<8.8% high school or lower) (HR, 1.26; 1.19-1.34). Conclusions Disparities in the risk for recurrent ASCVD events were present across sociodemographic factors among very high risk patients. The addition of sociodemographic factors to current definitions of very high risk could reduce health disparities.

Trends in Antihypertensive Medication Monotherapy and Combination Use Among US Adults, National Health and Nutrition Examination Survey 2005-2016.

Blood pressure (BP) control rates among US adults taking antihypertensive medication have not increased over the past decade. Many adults require 2 or more classes of antihypertensive medication to achieve guideline-recommended BP goals, but the proportion of US adults taking antihypertensive medication monotherapy, versus combination therapy, has not been quantified using contemporary data. We analyzed data from 2005 to 2008, 2009 to 2012, and 2013 to 2016 National Health and Nutrition Examination Surveys to determine trends in monotherapy and combinations of antihypertensive medication classes among US adults age ≥20 years with hypertension taking antihypertensive medication (n=7837). The proportion of US adults taking antihypertensive medication with uncontrolled BP (ie, systolic BP ≥140 or diastolic BP ≥90 mm Hg) was 32.3%, 30.2%, and 31.0% in 2005 to 2008, 2009 to 2012, and 2013 to 2016, respectively (Ptrend=0.37). Between 2005 to 2008 and 2013 to 2016, there was no evidence of changes in the proportions of US adults taking antihypertensive monotherapy (39.5%-40.4%, Ptrend=0.67), dual-therapy (37.9%-38.3%, Ptrend=0.75), triple-therapy (17.6%-16.5%, Ptrend=0.36), or quadruple-therapy (4.4%-4.3%, Ptrend=0.93). Between 2005 to 2008 and 2013 to 2016, there was no evidence of changes in the proportions of US adults with uncontrolled BP taking antihypertensive monotherapy (39.3%-40.6%, Ptrend=0.78). A high proportion of US adults with hypertension, including those with uncontrolled BP, are taking one antihypertensive medication class. Increasing the use of dual- and triple-therapy antihypertensive medication regimens may restore the upward trend in BP control rates among US adults.

Trends in Utilization of Statin Therapy and Contraindicated Statin Use in HIV--Infected Adults Treated With Antiretroviral Therapy From 2007 Through 2015.

Background HIV is associated with an increased risk for atherosclerotic cardiovascular disease, which may result in many people living with HIV taking a statin. Some statins are contraindicated with certain antiretroviral therapies ( ART ) and other medications commonly used by HIV -infected patients. Methods and Results We analyzed trends in the use of statins, including contraindicated statins, between 2007 and 2015 among HIV -infected patients aged ≥19 years taking ART who had employer-sponsored or Medicare supplemental health insurance in the Marketscan database (n=186 420). Statin use was identified using pharmacy claims. Contraindicated statin use was defined by a pharmacy claim for HIV protease inhibitors, cobicistat, hepatitis C protease inhibitors, anti-infectives, calcium channel blockers, amiodarone, gemfibrozil, or nefazodone followed by a fill for a contraindicated statin type and dosage within 90 days. The percentage of beneficiaries with HIV taking a statin remained unchanged between 2007 (24.6%) and 2015 (24.7%). Among those taking a statin, the percentage taking a contraindicated statin declined from 16.3% in 2007 to 9.0% in 2014 and then increased to 9.8% in 2015. The proportion of contraindicated statin fills attributable to HIV protease inhibitors declined from 63.9% in 2007 to 51.0% in 2015, while those attributable to cobicistat increased from 0% before 2012 to 20.6% in 2015. Conclusions Changes in ART regimens resulted in a decline in contraindicated statin use from 2007 to 2014, but this favorable trend was attenuated in 2015 because of increased use of cobicistat-containing ART regimens.

Risk Factors for Low Pharmacy Refill Adherence Among Older Hypertensive Men and Women by Race.

BACKGROUND: Sex-race stratification may lead to identification of risk factors for low antihypertensive medication adherence that are not apparent when assessing risk factors in women and men without race stratification. We examined risk factors associated with low pharmacy refill adherence across sex-race subgroups (white women, black women, white men, black men) within the Cohort Study of Medication Adherence among Older Adults (n = 2,122). METHODS: Pharmacy refill adherence was calculated as proportion of days covered using all antihypertensive prescriptions filled in the year prior to a baseline risk factor survey. Sex- and sex-race-stratified multivariable Poisson regression models with robust standard errors were used to estimate adjusted prevalence ratios and 95% confidence intervals for associations between participant characteristics and low adherence. RESULTS: Prevalence of low adherence was 22.9% vs. 40.7% in white vs. black women (P < 0.001) and 26.3% vs. 37.2% in white vs. black men (P = 0.003). In multivariable models, reducing antihypertensive medication due to cost was associated with low adherence within each sex-race subgroup. Additional factors associated with low adherence included shorter hypertension duration and comorbidities in white women; not being married and depressive symptoms in white men; and ≥6 primary care visits/year and complementary and alternative medicine use in black men. Among men, not being married and reporting depressive symptoms were associated with low adherence for whites, but not blacks. CONCLUSIONS: Identification of sex-race-specific risk factors for low antihypertensive medication adherence may guide development and implementation of tailored interventions to increase antihypertensive medication adherence and blood pressure control among older patients.

The Role of Nutraceuticals in Statin Intolerant Patients.

Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non-lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction.

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey).

BACKGROUND: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal of <120 versus <140 mm Hg among US adults at high cardiovascular disease risk but without diabetes mellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. METHODS: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, >1 g proteinuria, heart failure, estimated glomerular filtration rate <20 mL·min-1·1.73 m-2, or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for serious adverse events in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and serious adverse events incurred with intensive SBP treatment. RESULTS: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91-2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300-121 200) and give rise to 56 100 (95% CI, 50 800-61 400) episodes of hypotension, 34 400 (95% CI, 31 200-37 600) episodes of syncope, 43 400 (95% CI, 39 400-47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400-97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800-50 400) cases of heart failure annually. CONCLUSIONS: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events.

Impact of L-carnitine on plasma lipoprotein(a) concentrations: A systematic review and meta-analysis of randomized controlled trials.

We aimed to assess the impact of L-carnitine on plasma Lp(a) concentrations through systematic review and meta-analysis of available RCTs. The literature search included selected databases up to 31(st) January 2015. Meta-analysis was performed using fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The meta-analysis showed a significant reduction of Lp(a) levels following L-carnitine supplementation (WMD: -8.82 mg/dL, 95% CI: -10.09, -7.55, p < 0.001). When the studies were categorized according to the route of administration, a significant reduction in plasma Lp(a) concentration was observed with oral (WMD: -9.00 mg/dL, 95% CI: -10.29, -7.72, p < 0.001) but not intravenous L-carnitine (WMD: -2.91 mg/dL, 95% CI: -10.22, 4.41, p = 0.436). The results of the meta-regression analysis showed that the pooled estimate is independent of L-carnitine dose (slope: -0.30; 95% CI: -4.19, 3.59; p = 0.878) and duration of therapy (slope: 0.18; 95% CI: -0.22, 0.59; p = 0.374). In conclusion, the meta-analysis suggests a significant Lp(a) lowering by oral L-carnitine supplementation. Taking into account the limited number of available Lp(a)-targeted drugs, L-carnitine might be an effective alternative to effectively reduce Lp(a). Prospective outcome trials will be required to fully elucidate the clinical value and safety of oral L-carnitine supplementation.

Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of coenzyme Q10 (CoQ10) supplementation on statin-induced myopathy. PARTICIPANTS AND METHODS: We searched the MEDLINE, Cochrane Library, Scopus, and EMBASE databases (November 1, 1987, to May 1, 2014) to identify randomized controlled trials investigating the impact of CoQ10 on muscle pain and plasma creatine kinase (CK) activity as 2 measures of statin-induced myalgia. Two independent reviewers extracted data on study characteristics, methods, and outcomes. RESULTS: We included 6 studies with 302 patients receiving statin therapy: 5 studies with 226 participants evaluated the effect of CoQ10 supplementation on plasma CK activity, and 5 studies (4 used in the CK analysis and 1 other study) with 253 participants were included to assess the effect of CoQ10 supplementation on muscle pain. Compared with the control group, plasma CK activity was increased after CoQ10 supplementation, but this change was not significant (mean difference, 11.69 U/L [to convert to µkat/L, multiply by 0.0167]; 95% CI, -14.25 to 37.63 U/L; P=.38). Likewise, CoQ10 supplementation had no significant effect on muscle pain despite a trend toward a decrease (standardized mean difference, -0.53; 95% CI, -1.33 to 0.28; P=.20). No dose-effect association between changes in plasma CK activity (slope, -0.001; 95% CI, -0.004 to 0.001; P=.33) or in the indices of muscle pain (slope, 0.002; 95% CI, -0.005 to 0.010; P=.67) and administered doses of CoQ10 were observed. CONCLUSION: The results of this meta-analysis of available randomized controlled trials do not suggest any significant benefit of CoQ10 supplementation in improving statin-induced myopathy. Larger, well-designed trials are necessary to confirm the findings from this meta-analysis.

Analysis of vitamin D levels in patients with and without statin-associated myalgia - a systematic review and meta-analysis of 7 studies with 2420 patients.

INTRODUCTION: Vitamin D (vit D) deficiency may be associated with an increased risk of statin-related symptomatic myalgia in statin-treated patients. The aim of this meta-analysis was to substantiate the role of serum vitamin D levels in statin-associated myalgia. METHODS: The search included PUBMED, Cochrane Library, Scopus, and EMBASE from January 1, 1987 to April 1, 2014 to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes. Quantitative data synthesis was performed using a fixed-effect model. RESULTS: The electronic search yielded 437 articles; of those 20 were scrutinized as full texts and 13 studies were considered unsuitable. The final analysis included 7 studies with 2420 statin-treated patients divided into subgroups of patients with (n=666 [27.5%]) or without (n=1754) myalgia. Plasma vit D concentrations in the symptomatic and asymptomatic subgroups were 28.4±13.80ng/mL and 34.86±11.63ng/mL, respectively. The combination of data from individual observational studies showed that vit D plasma concentrations were significantly lower in patients with statin-associated myalgia compared with patients not manifesting this side effect (weighted mean difference -9.41ng/mL; 95% confidence interval: -10.17 to -8.64; p<0.00001). CONCLUSIONS: This meta-analysis provides evidence that low vit D levels are associated with myalgia in patients on statin therapy. Randomized controlled trials are necessary to establish whether vitamin D supplementation reduces the risk for statin-associated myalgia.

Psychometric properties of the Osteoporosis-specific Morisky Medication Adherence Scale in postmenopausal women with osteoporosis newly treated with bisphosphonates.

BACKGROUND: Poor adherence to oral osteoporosis medications is common. Strategies for improving adherence begin with identification of the problem. The 8-item Morisky Medication Adherence Scale for self-reported adherence to antihypertensive medications was modified for assessing adherence to oral osteoporosis medications. An evaluation of the measurement properties of the Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) was needed. OBJECTIVE: To examine the psychometric properties of the OS-MMAS in women with postmenopausal osteoporosis. METHODS: Five hundred women aged 55 years and older with osteoporosis who were newly prescribed daily or weekly oral bisphosphonates between May 15, 2010, and August 15, 2010, were randomly selected from Kaiser Permanente Southern California, a large integrated health care delivery system, and mailed a self-administered survey that included the 8-item OS-MMAS, Self-Efficacy for Appropriate Medication Use Scale (SEAMS), Beliefs about Medicines Questionnaire (BMQ), Treatment Satisfaction Questionnaire for Medication (TSQM), Gastrointestinal Symptom Rating Scale (GSRS), and 12-item Short-Form Health Survey (SF-12v2). OS-MMAS scores can range from 0 to 8, with higher scores indicating better medication adherence. Internal consistency reliability was evaluated using Cronbach α coefficient. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs) in a subset of 102 participants. Construct validity was assessed using confirmatory factor analysis and correlations between OS-MMAS and related measures. RESULTS: Of 197 participants, 150 reported that they were still taking their bisphosphonate at the time of the survey and completed the OS-MMAS. Overall, 30.7%, 32.7%, and 36.7% had low, medium, and high OS-MMAS scores (<6, 6 to <8, and 8, respectively). Cronbach α was 0.82 and the ICC was 0.77. Convergent validity was supported by significant correlations with SEAMS, BMQ necessity, and TSQM scores. In confirmatory factor analysis, a single-factor scale was supported. CONCLUSIONS: The OS-MMAS showed strong psychometric properties with good reliability and construct validity and may provide a valuable assessment of self-reported medication adherence in women newly prescribed oral osteoporosis medications.

Serum phosphorus predicts incident chronic kidney disease and end-stage renal disease.

BACKGROUND: Elevations in serum phosphorus are associated with renal decline in animal models and progression of established chronic kidney disease (CKD) in human observational studies. We examined whether serum phosphorus levels increase the risk of incident CKD or end-stage renal disease (ESRD) in two population-based prospective cohort studies. METHODS: Overall, 2269 participants free of CKD [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73(2)] from the Framingham Heart Study (FHS; mean age 42 years; 53% women) and 13,372 participants from the Third National Health and Nutrition Examination Survey (NHANES III; mean age 44.3 years, 52% women) contributed to the present study. In the FHS, we evaluated the relationship between baseline phosphorus category (<2.5 mg/dL, 2.5-3.49 mg/dL, 3.5-3.99 mg/dL and ≥4 mg/dL) and incident CKD (n = 267). In NHANES, we examined the relationship between phosphorus below and above 4 mg/dL in relation to incident ESRD (n = 65). RESULTS: FHS participants in the highest phosphorus category had an increased risk of CKD [odds ratio 2.14; 95% confidence interval (CI), 1.07-4.28; P = 0.03] in multivariable-adjusted models when compared to the referent group (2.5-3.49 mg/dL). Similarly, NHANES III participants with phosphorus levels ≥4 mg/dL demonstrated an increased risk of incident ESRD compared to those <4 mg/dL (relative risk 1.90; 95% CI 1.03-3.53; P = 0.04). CONCLUSIONS: In prospective studies of the general population, serum phosphorus levels in the upper-normal range were associated with a doubling in the risk of developing incident CKD and ESRD.

Vitamin D levels and food and environmental allergies in the United States: results from the National Health and Nutrition Examination Survey 2005-2006.

BACKGROUND: Previous research supports a possible link between low vitamin D levels and atopic disease. However, the association between low vitamin D levels and total and allergen-specific IgE levels has not been studied. OBJECTIVE: We sought to test the association between serum 25-hydroxyvitamin D (25[OH]D) deficiency (<15 ng/mL) and insufficiency (15-29 ng/mL) and allergic sensitization measured by serum IgE levels in a US nationally representative sample of 3136 children and adolescents and 3454 adults in the National Health and Nutrition Examination Survey 2005-2006. METHODS: The association of 25(OH)D deficiency with 17 different allergens was assessed after adjustment for potential confounders, including age; sex; race/ethnicity; obesity, low socioeconomic status; frequency of milk intake; daily hours spent watching television, playing videogames, or using a computer; serum cotinine levels; and vitamin D supplement use. RESULTS: In children and adolescents allergic sensitization to 11 of 17 allergens was more common in those with 25(OH)D deficiency. Compared with sufficient vitamin D levels of greater than 30 ng/mL, after multivariate adjustment, 25(OH)D levels of less than 15 ng/mL were associated with peanut (odds ratio [OR], 2.39; 95% CI, 1.29-4.45), ragweed (OR, 1.83; 95% CI, 1.20-2.80), and oak (OR, 4.75; 95% CI, 1.53-4.94) allergies (P < .01 for all). Eight other allergens were associated with 25(OH)D deficiency, with P values of less than .05 but greater than .01. There were no consistent associations seen between 25(OH)D levels and allergic sensitization in adults. CONCLUSION: Vitamin D deficiency is associated with higher levels of IgE sensitization in children and adolescents. Further research is needed to confirm these findings.

Adverse effects of complementary and alternative medicine on antihypertensive medication adherence: findings from the cohort study of medication adherence among older adults.

OBJECTIVES: To determine the association between complementary and alternative medicine (CAM) use and antihypertensive medication adherence in older black and white adults. DESIGN: Cross-sectional. SETTING: Patients enrolled in a managed care organization. PARTICIPANTS: Two thousand were hundred eighty black and white adults aged 65 and older and prescribed antihypertensive medication. MEASUREMENTS: Information on CAM use (health food and herbal supplements, relaxation techniques) for blood pressure control and antihypertensive medication adherence were collected in a telephone survey between August 2006 and September 2007. Low medication adherence was defined as a score less than 6 using the eight-item Morisky Medication Adherence Scale. RESULTS: The mean age of participants was 75.0+/-5.6, 30.7% were black, 26.5% used CAM, and 14.1% had low antihypertensive medication adherence. In managing blood pressure, 30.5% of black and 24.7% of white participants had used CAM in the last year (P=.005), and 18.4% of black and 12.3% of white participants reported low adherence to antihypertensive medication (<.001). After multivariable adjustment for sociodemographic information, depressive symptoms, and reduction in antihypertensive medications because of cost, the prevalence ratios of low antihypertensive medication adherence associated with CAM use were 1.56 (95% confidence interval (CI)=1.14-2.15; P=.006) in blacks and 0.95 (95% CI=0.70-1.29; P=.73) in whites (P value for interaction=.07). CONCLUSION: In this cohort of older managed care patients, CAM use was associated with low adherence to antihypertensive medication in blacks but not whites.

Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001-2004.

OBJECTIVES: To determine the prevalence of 25-hydroxyvitamin D (25[OH]D) deficiency and associations between 25(OH)D deficiency and cardiovascular risk factors in children and adolescents. METHODS: With a nationally representative sample of children aged 1 to 21 years in the National Health and Nutrition Examination Survey 2001-2004 (n = 6275), we measured serum 25(OH)D deficiency and insufficiency (25[OH]D <15 ng/mL and 15-29 ng/mL, respectively) and cardiovascular risk factors. RESULTS: Overall, 9% of the pediatric population, representing 7.6 million US children and adolescents, were 25(OH)D deficient and 61%, representing 50.8 million US children and adolescents, were 25(OH)D insufficient. Only 4% had taken 400 IU of vitamin D per day for the past 30 days. After multivariable adjustment, those who were older (odds ratio [OR]: 1.16 [95% confidence interval (CI): 1.12 to 1.20] per year of age), girls (OR: 1.9 [1.6 to 2.4]), non-Hispanic black (OR: 21.9 [13.4 to 35.7]) or Mexican-American (OR: 3.5 [1.9 to 6.4]) compared with non-Hispanic white, obese (OR: 1.9 [1.5 to 2.5]), and those who drank milk less than once a week (OR: 2.9 [2.1 to 3.9]) or used >4 hours of television, video, or computers per day (OR: 1.6 [1.1 to 2.3]) were more likely to be 25(OH)D deficient. Those who used vitamin D supplementation were less likely (OR: 0.4 [0.2 to 0.8]) to be 25(OH)D deficient. Also, after multivariable adjustment, 25(OH)D deficiency was associated with elevated parathyroid hormone levels (OR: 3.6; [1.8 to 7.1]), higher systolic blood pressure (OR: 2.24 mmHg [0.98 to 3.50 mmHg]), and lower serum calcium (OR: -0.10 mg/dL [-0.15 to -0.04 mg/dL]) and high-density lipoprotein cholesterol (OR: -3.03 mg/dL [-5.02 to -1.04]) levels compared with those with 25(OH)D levels > or =30 ng/mL. CONCLUSIONS: 25(OH)D deficiency is common in the general US pediatric population and is associated with adverse cardiovascular risks.