Accumulation of non-traditional risk factors for coronary heart disease is associated with incident coronary heart disease hospitalization and death

Assessing multiple traditional risk factors improves prediction for late-life diseases, including coronary heart disease (CHD). It appears that non-traditional risk factors can also predict risk. The objective was to investigate contributions of non-traditional risk factors to coronary heart disease risk using a deficit accumulation approach.Community-dwelling adults with no known history of CHD (n = 2195, mean age 46.9±18.7 years, 51.8% women) participated in the 1995 Nova Scotia Health Survey. Three risk factor indices were constructed to quantify the proportion of deficits present in individuals: 1) a 17-item Non-Traditional Risk Factor Index (e.g. sinusitis, arthritis); 2) a 9-item Traditional Risk Factor Index (e.g. hypertension, diabetes); and 3) a frailty index (25 items combined from the other two index measures). Ten-year risks of CHD events (defined as CHD-related hospitalization and CHD-related mortality) were evaluated.The Non-Traditional Risk Factor Index, made up of health deficits unrelated to CHD, was independently associated with incident CHD events over 10 years after controlling for age, sex, and the Traditional Risk Factor Index [adjusted {adj.} Hazard Ratio {HR} = 1.31; Confidence Interval {CI} 1.14-1.51]. When all health deficits, both those related and unrelated to CHD, were included in a frailty index the corresponding adjusted hazard ratio was 1.61; CI 1.40-1.85.Both traditional and non-traditional risk factor indices are independently associated with incident CHD events. CHD risk assessment may benefit from consideration of general health information as well as from traditional risk factors.Lindsay M. K. Wallace, Olga Theou, Susan A. Kirkland, Michael R. H. Rockwood, Karina W. Davidson, Daichi Shimbo, Kenneth Rockwoo

Antihypertensive Medication Classes Used among Medicare Beneficiaries Initiating Treatment in 2007–2010

Background After the 2003 publication of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines, there was a 5–10% increase in patients initiating antihypertensive medication with a thiazide-type diuretic, but most patients still did not initiate treatment with this class. There are few contemporary published data on antihypertensive medication classes filled by patients initiating treatment. Methods and Findings We used the 5% random Medicare sample to study the initiation of antihypertensive medication between 2007 and 2010. Initiation was defined by the first antihypertensive medication fill preceded by 365 days with no antihypertensive medication fills. We restricted our analysis to beneficiaries ≥65 years who had two or more outpatient visits with a hypertension diagnosis and full Medicare fee-for-service coverage for the 365 days prior to initiation of antihypertensive medication. Between 2007 and 2010, 32,142 beneficiaries in the 5% Medicare sample initiated antihypertensive medication. Initiation with a thiazide-type diuretic decreased from 19.2% in 2007 to 17.9% in 2010. No other changes in medication classes initiated occurred over this period. Among those initiating antihypertensive medication in 2010, 31.3% filled angiotensin-converting enzyme inhibitors (ACE-Is), 26.9% filled beta blockers, 17.2% filled calcium channel blockers, and 14.4% filled angiotensin receptor blockers (ARBs). Initiation with %#62;1 antihypertensive medication class decreased from 25.6% in 2007 to 24.1% in 2010. Patients initiated >1 antihypertensive medication class most commonly with a thiazide-type diuretic and either an ACE-I or ARB. Conclusion These results suggest that JNC 7 had a limited long-term impact on the choice of antihypertensive medication class and provide baseline data prior to the publication of the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults from the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)

Diurnal blood pressure pattern and development of prehypertension or hypertension in young adults: the CARDIA study

Nondippers (people whose sleep systolic blood pressure [SBP] fails to decrease >10% from daytime SBP) have increased risk of cardiovascular disease. The prevalence of nondipping in younger adults has not been well studied, nor has its value for predicting hypertension. We examined the prevalence of nondipping in a substudy of the Coronary Artery Risk Development in Young Adults (CARDIA) Study. We used Cox regression to estimate the hazard ratio (HR) conferred by nondipping for incident prehypertension or hypertension (preHTN/HTN) over 15 years. Of the 264 nonhypertensive participants at baseline, 118 (45%) were nondippers. Blacks were more likely than whites to be nondippers (52% versus 33%, P = .004). The incidence rate of preHTN/HTN was 29.2/1000 person-years among dippers and 36.2/1000 person-years among nondippers. Compared with those in the lowest quartile of nighttime to daytime SBP, those in the highest quartile were more likely to develop preHTN/HTN (HR 1.61; P = .06), but this relationship was attenuated after adjustment (HR 1.34; P = .27). Our results demonstrate that nondipping is common in young, nonhypertensive adults, and is more common in blacks than whites. Nondipping might predate a meaningful clinically detected increase in BP in some people, but more research in larger study samples is needed

Higher leptin is associated with hypertension: the Multi-Ethnic Study of Atherosclerosis

Adipokines are secreted from adipose tissue, influence energy homeostasis and may contribute to the association between obesity and hypertension. Among 1897 participants enrolled in the Multi-Ethnic Study of Atherosclerosis, we examined associations between blood pressure and leptin, tumor necrosis factor-α (TNFα), resistin and total adiponectin. The mean age and body mass index (BMI) was 64.7 years and 28.1, respectively, and 50% were female. After adjustment for risk factors, a 1-s.d.-increment higher leptin level was significantly associated with higher systolic (5.0 mm Hg), diastolic (1.9), mean arterial (2.8) and pulse pressures (3.6), as well as a 34% higher odds for being hypertensive (P<0.01 for all). These associations were not materially different when the other adipokines, as well as BMI, waist circumference or waist-to-hip ratio, were additionally added to the model. Notably, the associations between leptin and hypertension were stronger in men, but were not different by race/ethnic group, BMI or smoking status. Adiponectin, resistin and TNFα were not independently associated with blood pressure or hypertension. Higher serum leptin, but not adiponectin, resistin or TNFα, is associated with higher levels of all measures of blood pressure, as well as a higher odds of hypertension, independent of risk factors, anthropometric measures and other selected adipokines

Levels of Office Blood Pressure and Their Operating Characteristics for Detecting Masked Hypertension Based on Ambulatory Blood Pressure Monitoring

BACKGROUND Masked hypertension (MH)—nonelevated office blood pressure (BP) with elevated out-of-office BP average—conveys cardiovascular risk similar to or approaching sustained hypertension, making its detection of potential clinical importance. However, it may not be feasible or cost-effective to perform ambulatory BP monitoring (ABPM) on all patients with a nonelevated office BP. There likely exists a level of office BP below which ABPM is not warranted because the probability of MH is low. METHODS We analyzed data from 294 adults aged ≥30 years not on BP-lowering medication with office BP <140/90mm Hg, all of whom underwent 24-hour ABPM. We calculated sensitivity, false-positive rate, and likelihood ratios (LRs) for the range of office BP cutoffs from 110 to 138mm Hg systolic and from 68 to 88mm Hg diastolic for detecting MH. RESULTS The systolic BP cutoff with the highest +LR for detecting MH (1.8) was 120mm Hg, and the diastolic cutoff with the highest +LR (2.4) was 82mm Hg. However, the systolic level of 120mm Hg had a false-positive rate of 42%, and the diastolic level of 82mm Hg had a sensitivity of only 39%. CONCLUSIONS The cutoff of office BP with the best overall operating characteristics for diagnosing MH is approximately 120/82mm Hg. However, this cutoff may have an unacceptably high false-positive rate. Clinical risk tools to identify patients with nonelevated office BP for whom ABPM should be considered will likely need to include factors in addition to office BP

Associations of Aortic Distensibility and Arterial Elasticity With Long-Term Visit-to-Visit Blood Pressure Variability: The Multi-Ethnic Study of Atherosclerosis (MESA)

BACKGROUND Although higher visit-to-visit variability (VVV) of blood pressure (BP) is associated with increased cardiovascular disease risk, the physiological basis for VVV of BP is incompletely understood. METHODS We examined the associations of aortic distensibility (assessed by magnetic resonance imaging) and artery elasticity indices (determined by radial artery pulse contour analysis) with VVV of BP in 2,640 and 4,560 participants, respectively, from the Multi-Ethnic Study of Atherosclerosis. Arterial measures were obtained at exam 1. BP readings were taken at exam 1 and at 3 follow-up visits at 18-month intervals (exams 2, 3, and 4). VVV was defined as the SD about each participant’s mean systolic BP (SBP) across visits. RESULTS The mean SDs of SBP were inversely associated with aortic distensibility: 7.7, 9.9, 10.9, and 13.2mm Hg for quartiles 4, 3, 2, and 1 of aortic distensibility, respectively (P trend < 0.001). This association remained significant after adjustment for demographics, cardiovascular risk factors, mean SBP, and antihypertensive medication use (P trend < 0.01). In a fully adjusted model, lower quartiles of large artery and small artery elasticity (LAE and SAE) indices were also associated with higher mean SD of SBP (P trend = 0.02 for LAE; P trend < 0.001 for SAE). CONCLUSIONS In this multiethnic cohort, functional alterations of central and peripheral arteries were associated with greater long-term VVV of SBP

A Pilot Study Identifying Statin Nonadherence With Visit-to-Visit Variability of Low-Density Lipoprotein Cholesterol

Nonadherence to cardiovascular medications such as statins is a common, important problem. Clinicians currently rely on intuition to identify medication nonadherence. The visit-to-visit variability (VVV) of low-density lipoprotein (LDL) cholesterol might represent an opportunity to identify statin nonadherence with greater accuracy. We examined the clinical and pharmacy data from 782 members of the Boston Medical Center Health Plan, seen at either the Boston Medical Center or its affiliated community health centers, who were taking statins and had ≥3 LDL cholesterol measurements from 2008 to 2011. The LDL cholesterol VVV (defined by the within-patient SD) was categorized into quintiles. Multivariate logistic regression models were generated with statin nonadherence (defined by the standard 80% pharmacy refill-based medication possession ratio threshold) as the dependent variable. The proportion of statin nonadherence increased across the quintiles of LDL cholesterol VVV (64.3%, 71.2%, 89.2%, 92.3%, 91.7%). Higher quintiles of LDL cholesterol VVV had a strong positive association with statin nonadherence, with an adjusted odds ratio of 3.4 (95% confidence interval 1.7 to 7.1) in the highest versus lowest quintile of LDL cholesterol VVV. The age- and gender-adjusted model had poor discrimination (C-statistic 0.62, 95% confidence interval 0.57 to 0.67), but the final adjusted model (age, gender, race, mean LDL cholesterol) demonstrated good discrimination (C-statistic 0.75, 95% confidence interval 0.71 to 0.79) between the adherent and nonadherent patients. In conclusion, the VVV of LDL cholesterol demonstrated a strong association with statin nonadherence in a clinic setting. Furthermore, a VVV of LDL cholesterol-based model had good discrimination characteristics for statin nonadherence. Research is needed to validate and generalize these findings to other populations and biomarkers

CHD4 and the NuRD complex directly control cardiac sarcomere formation

Cardiac development relies on proper cardiomyocyte differentiation, including expression and assembly of cell-type-specific actomyosin subunits into a functional cardiac sarcomere. Control of this process involves not only promoting expression of cardiac sarcomere subunits but also repressing expression of noncardiac myofibril paralogs. This level of transcriptional control requires broadly expressed multiprotein machines that modify and remodel the chromatin landscape to restrict transcription machinery access. Prominent among these is the nucleosome remodeling and deacetylase (NuRD) complex, which includes the catalytic core subunit CHD4. Here, we demonstrate that direct CHD4-mediated repression of skeletal and smooth muscle myofibril isoforms is required for normal cardiac sarcomere formation, function, and embryonic survival early in gestation. Through transcriptomic and genome-wide analyses of CHD4 localization, we identified unique CHD4 binding sites in smooth muscle myosin heavy chain, fast skeletal α-actin, and the fast skeletal troponin complex genes. We further demonstrate that in the absence of CHD4, cardiomyocytes in the developing heart form a hybrid muscle cell that contains cardiac, skeletal, and smooth muscle myofibril components. These misexpressed paralogs intercalate into the nascent cardiac sarcomere to disrupt sarcomere formation and cause impaired cardiac function in utero. These results demonstrate the genomic and physiological requirements for CHD4 in mammalian cardiac development

Nighttime Blood Pressure Dipping in Young Adults and Coronary Artery Calcium 10-15 Years Later: The Coronary Artery Risk Development in Young Adults Study

Nighttime blood pressure (BP) dipping can be quantified as the ratio of mean nighttime (sleep) BP to mean daytime (awake) BP. People whose dipping ratio is 0.90 have been referred to as nondippers, and nondipping is associated with cardiovascular disease events. We examined the relationship between systolic nighttime BP dipping in young adults and presence of coronary artery calcium (CAC) 10-15 years later using data from the ambulatory BP monitoring substudy of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Among 239 participants with adequate measures of both nighttime and daytime readings and coronary artery calcium, the systolic BP dipping ratio ranged from 0.72 to 1.24 (mean 0.88, SD 0.06), and CAC was present 10 to 15 years later in 54 participants (22.6%). Compared to those whose systolic BP dipping ratio ranged from 0.88 to 0.92 (Quartile 3), the 57 participants (23.9%) with less pronounced or absent dipping (ratio 0.92 to 1.24, Quartile 4) had an unadjusted odds ratio of 4.08 (95% CI 1.48-11.2) for presence of CAC. The 60 participants (25.1%) with a more pronounced dipping (ratio 0.72 to 0.85, Quartile 1) also had greater odds for presence of CAC (OR 4.76; 95% CI 1.76-12.9). When modeled as a continuous predictor, a U-shaped relationship between systolic BP dipping ratio and future CAC was apparent, and persisted after adjustment for multiple potential confounders (

Longitudinal Patterns of Change in Systolic Blood Pressure and Incidence of Cardiovascular DiseaseNovelty and Significance: The Atherosclerosis Risk in Communities Study

Elevated blood pressure in mid-life contributes significantly to the risk of cardiovascular disease. However, patterns of blood pressure increase may differ among individuals and may result in differential risk. Our goal was to examine the contribution of longitudinal patterns of blood pressure change to incidence of heart failure, coronary heart disease, stroke and cardiovascular disease mortality