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BACKGROUND Several ambulatory blood pressure monitoring (ABPM) measures have been associated with increased cardiovascular disease risk independent of clinic blood pressure (BP). African Americans have higher clinic BP compared with Whites but few data are available on racial differences in ABPM measures. METHODS We compared ABPM measures between African American (n = 178) and White (n = 103) participants at the Year 5 Coronary Artery Risk Development in Young Adults study visit. BP was measured during a study visit and the second and third measurements were averaged. ABPM was conducted over the following 24 hours. RESULTS Mean ± SD age of participants was 29.8±3.8 years and 30.8±3.5 years for African Americans and Whites, respectively. Mean daytime systolic BP (SBP) was 3.90 (SD 1.18) mm Hg higher among African Americans compared with Whites (P < 0.001) after age–gender adjustment and 1.71 (SD 1.03) mm Hg higher after multivariable adjustment including mean clinic SBP (P = 0.10). After multivariable adjustment including mean clinic SBP, nighttime SBP was 4.83 (SD 1.11) mm Hg higher among African Americans compared with Whites (P < 0.001). After multivariable adjustment, the African Americans were more likely than Whites to have nocturnal hypertension (prevalence ratio: 2.44, 95% CI: 0.99–6.05) and nondipping (prevalence ratio: 2.50, 95% CI: 1.39–4.48). The prevalence of masked hypertension among African Americans and Whites was 4.4% and 2.1%, respectively, (P = 0.49) and white coat hypertension was 3.3% and 3.9%, respectively (P = 0.99). Twenty-four hour BP variability on ABPM was higher among African Americans compared with Whites. CONCLUSIONS These data suggest racial differences in several ABPM measures exist.

Objective. Type 2 diabetes mellitus (T2DM) is known to be associated with increased cardiovascular risk. The aim of this study was therefore to investigate the independent effects of hyperglycaemia, hypoglycaemia, and glucose variability on microvascular and macrovascular disease in T2DM. Methods. Subjects with T2DM of <10 years duration and on stable antiglycaemic treatment underwent carotid intima-media thickness (CIMT), ankle-brachial index (ABI), albumin-creatinine ratio (ACR), and HbA1c measurement, as well as 72-hour continuous glucose monitoring. Macrovascular disease was defined as one or more of the following: history of ischaemic heart disease (IHD), cerebrovascular accident (CVA), ABI < 0.9, or abnormal CIMT. Results. The study population comprised 121 subjects with T2DM (89 males : 32 females). The mean age was 62.6 years, and the mean DM duration was 3.7 years. Macrovascular disease was present in 71 patients (58.7%). In multivariate logistic regression analysis, body surface area (BSA) (OR 18.88 (95% CI 2.20–156.69), p=0.006) and duration of blood glucose (BG) < 3.9 mmol/L (OR 1.12 (95% CI 1.014–1.228), p=0.024) were independent predictors of macrovascular disease. BSA (OR 12.6 (95% CI 1.70–93.54), p=0.013) and duration of BG < 3.9 mmol/L (OR 1.09 (95% CI 1.003–1.187), p=0.041) were independent predictors of abnormal CIMT. Area under the curve for BG > 7.8 mmol/L (β = 15.83, p=0.005) was the sole independent predictor of albuminuria in generalised linear regression. Conclusions. This study demonstrates that hypoglycaemia is associated with the occurrence of atherosclerotic disease while hyperglycaemia is associated with microvascular disease in a Caucasian population with T2DM of recent duration.

This study sought to evaluate the impact of race/ethnicity on cardiovascular risk factor control and on clinical outcomes in a setting of comparable access to medical care. The BARI 2D trial enrolled 1,750 participants from the United States and Canada that self-reported either White non-Hispanic (n = 1,189), Black non-Hispanic (n = 349), or Hispanic (n = 212) race/ethnicity. Participants had type 2 diabetes and coronary artery disease and were randomized to cardiac and glycemic treatment strategies. All patients received intensive target-based medical treatment for cardiac risk factors. Average follow-up was 5.3 years. Kaplan-Meier survival curves and Cox proportional hazards regression models were constructed to assess potential differences in mortality and cardiovascular outcomes across racial/ethnic groups. Long-term risk of death and death/myocardial infarction/stroke did not vary significantly by race/ethnicity (5-year death: 11.0% Whites, 13.7% Blacks, 8.7% Hispanics, p = 0.19; adjusted hazard ratio 1.18 Black versus White, 95% confidence interval 0.84 to 1.67, p = 0.33 and 0.82 Hispanic versus White, 95% confidence interval 0.51 to 1.34, p = 0.43). Among the 1,168 patients with suboptimal risk factor control at baseline, the ability to attain better risk factor control during the trial was associated with higher 5-year survival (71%, 86% and 95% for patients with 0 or 1, 2, and 3 factors in control, respectively, p <0.001); this pattern was observed within each race/ethnic group. In conclusion, significant race/ethnic differences in cardiac risk profiles that persisted during follow-up did not translate into significant differences in 5-year death or death/MI/stroke.

The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was undertaken to determine whether early revascularization intervention is superior to deferred intervention in the presence of aggressive medical therapy and whether antidiabetes regimens targeting insulin sensitivity are more or less effective than regimens targeting insulin provision in reducing cardiovascular events among patients with type 2 diabetes mellitus and stable coronary artery disease (CAD). The BARI 2D trial is a National Institutes of Health–sponsored randomized clinical trial with a 2 × 2 factorial design. Between 2001 and 2005, 49 clinical sites in North America, South America, and Europe randomized 2,368 patients. At baseline, the trial collected data on clinical history, symptoms, and medications along with centralized evaluations of angiograms, electrocardiograms, and blood and urine specimens. Most of the BARI 2D patients were referred from the cardiac catheterization laboratory (54%) or cardiology clinic (27%). Of the randomized participants, 30% were women, 34% were minorities, 61% had angina, and 67% had multiregion CAD. Moreover, 29% had been treated with insulin, 58% had hemoglobin A 1c >7.0%, 41% had low-density lipoprotein cholesterol ≥100 mg/dL, 52% had blood pressure >130/80 mm Hg, and 56% had body mass index ≥30 kg/m 2. Baseline characteristics in BARI 2D are well balanced between the randomized treatment groups, and the clinical profile of the study cohort is representative of the target population. As a result, the BARI 2D clinical trial is in an excellent position to evaluate alternative treatment approaches for diabetes and CAD.

Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1–100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants. Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. National Institute on Aging, National Institutes of Health; St Luke's Hospital of Kansas City; and Paleocardiology Foundation.

The absence of coronary artery calcification (CAC) has been used to as an indication to rule out significant coronary artery disease (CAD). However, diagnostic usefulness of ‘zero calcium score criteria’ as a decision-making strategy to rule out significant CAD as the etiology of acute chest pain has not been studied in depth, especially in Asian ethnicity. We prospectively enrolled 136 Korean patients (58% men, 56 ± 13 years) who presented to the emergency department (ED) with acute chest pain and non-diagnostic ECG. All patients underwent 64-slice CT for calcium scoring and coronary CT angiography (cCTA). We investigated the association of CAC with the presence of ≥50% CAD on cCTA and with a final diagnosis of an acute coronary syndrome (ACS). Ninety-two patients out of 136 (68%) did not show detectable CAC, and 14 out of these 92 without CAC (15%) had ≥50% CAD on cCTA. Sensitivity, specificity, positive predictive value and negative predictive value of zero calcium score criteria for the detection of ≥50% CAD were 0.66 (95% confidence interval, 0.50–0.80), 0.83 (0.74–0.90), 0.64 (0.48–0.77), 0.85 (0.75–0.91), respectively. Patients who had ≥50% CAD without detectable CAC were younger ( P  = 0.001), and had a higher prevalence of smoking ( P  = 0.048) as compared to patients with a degree of CAC. Most of the patients with ≥50% CAD of non-calcified plaque were younger than 60 years of age (79%, 11/14), however, 3 of them were older than 60 years of age. Forty-five patients (33%) were subsequently diagnosed as having ACS, and 38% (17/45) of them had no CAC. Zero calcium score did not necessarily guarantee the absence of significant CAD, even in patients older than 60 years, in Asian ethnicity presenting to the ED with chest pain.

The α-adducin ( ADD1) Gly460Trp polymorphism has been associated with hypertension and response to diuretic therapy, but controversy exists. The present study was conducted to prospectively investigate the relationship among the ADD1 Gly460Trp polymorphism, diuretic use, and adverse cardiovascular outcomes among 5,979 patients with hypertensive coronary artery disease, who participated in the INVEST and provided genomic DNA. The primary outcome was defined as the first occurrence of nonfatal stroke, nonfatal myocardial infarction, or all-cause death. Secondary outcomes were the components of the primary outcome. Ancestry informative markers were used to control for population stratification. In blacks, ADD1 variant carriers were at higher risk for a primary outcome event than wild-type homozygotes (adjusted hazard ratio 2.62, 95% CI 1.23-5.58, P = .012), with a similar trend in whites and Hispanics, albeit a smaller magnitude of effect (adjusted hazard ratio 1.43, 0.86-2.39 in Hispanics; 1.24, 0.90-1.71 in whites). Secondary outcome analysis showed that the all-cause death was driving the differences in primary outcomes by genotype. There was no interaction between the ADD1 polymorphism and diuretic use for either primary outcome or secondary outcomes. In hypertensive patients with coronary artery disease, black ADD1 variant carriers showed a 2.6-fold excess risk for a primary outcome event and an 8-fold increase risk of death. White and Hispanic ADD1 variant carriers showed an increased but nonsignificant excess risk. However, the effect of diuretic use on risk of cardiovascular outcomes did not vary by ADD1 carrier status.

Recent studies in animal models and humans show that long non-coding RNAs (lncRNAs) are involved in the development of atherosclerosis, which contributes to the pathological foundation of coronary artery disease (CAD). LncRNAs in plasma and serum have been considered as promising novel biomarkers for diagnosis and prognosis of cardiovascular diseases, especially CAD. We here measured the circulating levels of 8 individual lncRNAs which are known to be relevant to atherosclerosis in the plasma samples from 300 patients with CAD and 180 control subjects by using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) methods. We found that the plasma level of H19 and long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) were significantly increased in patients with CAD. The area under the receiver operating characteristic curve was 0.631 for H19 and 0.722 for LIPCAR. Multivariate logistic regression analyses indicated that plasma H19 and LIPCAR were independent predictors for CAD, even after adjustment for traditional cardiovascular risk factors. Further studies identified that plasma levels of H19 and LIPCAR were also increased in CAD patients with heart failure compared to those with normal cardiac function. Taken together, our results suggest that increased plasma levels of H19 and LIPCAR are associated with increased risk of CAD and may be considered as novel biomarkers for CAD.

In an analysis from the Multi-Ethnic Study of Atherosclerosis, 6722 men and women without cardiovascular disease from four ethnic groups underwent coronary calcium scanning and were followed for a median of 3.8 years. For each ethnic group, there was an increase in the risk of subsequent coronary events with an increase in the baseline coronary calcium score. Men and women without cardiovascular disease from four ethnic groups underwent coronary calcium scanning and were followed for a median of 3.8 years. For each racial or ethnic group, there was an increase in the risk of subsequent coronary events with an increase in the baseline coronary calcium score. The Framingham risk score uses standard risk factors to estimate the risk of coronary events in persons without previous coronary heart disease. 1 , 2 However, because this score predicts coronary events only moderately well, researchers have explored other methods to identify patients who would benefit most from intensive prevention efforts. 3 – 7 Radiographically detectable coronary-artery calcium is a marker of subclinical coronary heart disease and predicts coronary events in white populations. 8 – 18 As a result, there has been considerable interest in the potential use of measurements of coronary-artery calcium in models of risk prediction. The potential role of this variable as a . . .

A meta-analysis of exome-wide association studies for blood lipid levels in East Asian populations identifies a novel coding variant. Exome array data from the Global Lipids Genetics Consortium were integrated and led to the discovery of novel and population-specific variants associated with cholesterol and triglycerides. Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian–specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.