Incident Cardiovascular Outcomes Research Articles

Consequences of Comorbidity of Elevated Stress and/or Depressive Symptoms and Incident Cardiovascular Outcomes in Diabetes: Results From the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study.

OBJECTIVETo evaluate the impact of comorbid depressive symptoms and/or stress on adverse cardiovascular (CV) outcomes in individuals with diabetes compared with those without diabetes.RESEARCH DESIGN AND METHODSInvestigators examined the relationship between baseline depressive symptoms and/or stress in adults with and without diabetes and physician-adjudicated incident CV outcomes including stroke, myocardial infarction/acute coronary heart disease, and CV death over a median follow-up of 5.95 years in the national REGARDS cohort study.RESULTSSubjects included 22,003 adults (4,090 with diabetes) (mean age 64 years, 58% female, 42% black, and 56% living in the southeastern “Stroke Belt”). Elevated stress and/or depressive symptoms were more common in subjects with diabetes (36.8% vs. 29.5%; P < 0.001). In fully adjusted models, reporting either elevated stress or depressive symptoms was associated with a significantly increased incidence of stroke (HR 1.57 [95% CI 1.05, 2.33] vs. 1.01 [0.79, 1.30]) and CV death (1.53 [1.08, 2.17] vs. 1.12 [0.90, 1.38]) in subjects with diabetes but not in those without diabetes. The combination of both elevated stress and depressive symptoms in subjects with diabetes was associated with a higher incidence of CV death (2.15 [1.33, 3.47]) than either behavioral comorbidity alone (1.53 [1.08, 2.17]) and higher than in those with both elevated stress and depressive symptoms but without diabetes (1.27 [0.86, 1.88]).CONCLUSIONSComorbid stress and/or depressive symptoms are common in individuals with diabetes and together are associated with progressively increased risks for adverse CV outcomes.

Abstract 15509: Circulating Ceramides Predict Fatal and All Incident Major Adverse Cardiovascular Events: A Prospective Analysis of the FINRISK 2002 Cohort

Introduction: Ceramides are molecular lipids assumed to play a role in apoptosis, inflammation, obesity and insulin resistance. A recent study reported that certain ceramides were associated with fatal outcome among patients with CHD. Hypothesis: We hypothesized that ceramides are associated with incident cardiovascular (CVD) outcomes among apparently healthy individuals over and above the traditional risk factors. Methods: FINRISK 2002 is a population-based risk factor survey, which recruited 8,798 men and women aged 25-74 years. The participation rate was 65.5%. The cohort was followed up through 31 Dec, 2011, for incident CVD events and through 31 Dec, 2012, for deaths. Our primary outcome was major adverse cardiovascular events (MACE, n= 471). Secondary analyses were carried out for fatal MACE (n=137). Four circulating ceramides (Cer d18:1/16:0, Cer d18:1/18:0, Cer d18:1/24:0, and Cer d18:1/24:1) were determined from frozen samples using mass spectrometry. We used Cox proportional hazard models with age as the time scale to determine associations of the ceramides with incident outcomes. All models were stratified by sex and the full models were adjusted for geographic region, total and HDL-cholesterol, systolic blood pressure, blood pressure medication, BMI, smoking and diabetes. The predictive ability of the ceramides was assessed by estimating the 10-year absolute risk of MACE and comparing the full models with and without ceramides. The predictions were done using 10-fold cross-validated Weibull proportional hazard models. Results: When considered one by one, three out of the four ceramides were significantly associated with the risk of incident MACE in the fully adjusted Cox models. Ceramide score, formed as a linear combination of the four ceramides had a hazard ratio (HR) of 1.75 (p=0.005) in the full model. C-statistics did not change significantly but the net reclassification improvement among persons with intermediate risk was significant 6.2% (2.6 - 9.7%). The association of the ceramide score with fatal MACE was even stronger than with all MACE: HR=2.31 (p=0.02). Conclusions: These results show the potential of lipidomics profiling in producing new insights in the pathogenesis of CVD and suggesting new therapeutic targets.

Abstract 12490: Class I Indications for Statin Therapy in Primary Prevention by Three Cholesterol Guidelines and Risk of Incident Cardiovascular Outcomes: Multi-ethnic Study of Atherosclerosis (MESA)

Introduction: The major societal guidelines on cholesterol treatment (2013 ACC/AHA, 2004 NCEP/ATP III, and the 2011 ESC/EAS) differ in identifying patients with a class 1 recommendation for statin therapy for atherosclerotic cardiovascular disease (ASCVD). ACC/AHA emphasizes a need for clinician-patient dialogue on the risks/benefits of statins in primary prevention of ASCVD. Limited data exist on the accuracy of statin-eligibility (Class I) for ASCVD events to inform this dialogue. We assessed the accuracy of class I statin eligibility with incident ASCVD events by ACC/AHA compared with NCEP/ATP III and ESC/EAS guidelines. Methods: We evaluated the sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) of class I recommendation for statin therapy by each guideline for respective 10 yr. adjudicated incident ASCVD outcomes [NCEP/ATP III- MI, CHD death; ACC/AHA- MI, CHD death, fatal/non-fatal strokes; ESC/EAS: ASCVD death] in participants of the Multi Ethnic Study of Atherosclerosis. We stratified analysis by age, sex, and race. 4723 out of 6814 persons, not on statins at baseline, had complete data. Results: Mean age was 59±9 yrs., 47% male, 37% white, 28% African American (AA), 23% Hispanic, and 12% Asian, 7.5% T2DM, 15%/35% current/former smokers, and mean BMI of 28±6 kg/m2. 7.3% had ASCVD, 5.2% ASCVD death and 5.1% had a CHD event after 10 yrs. See Table 1 for results. Subgroup analysis shows AHA/ACC had a higher SN and lower SP in men vs. women (SN = 76% vs. 46%, SP = 54% vs. 77%) and in those &gt;60 vs. &lt;60 yrs (SN = 79% vs. 40%, SP = 41% vs. 85%). For AHA/ACC, SN was highest in Asians (75%) followed by AA (74%), Hispanics (56%), whites (56%). SP in whites (70%), Hispanics (68%), Asians (68%), AA (60%) Conclusions: Class I statin indication by all 3 guidelines have relatively low sensitivities for a good screening tool. ACC/AHA has higher SN, lower SP, similar NPV and higher PPV compared with NCEP/ATP III and ESC/EAS for primary ASCVD events.

Target organ complications and prognostic significance of alerting reaction: analysis from the Dallas Heart Study.

Noninvasive blood pressure (BP) measurement often triggers a transient rise in BP, known as an alerting reaction. However, the prevalence and prognostic significance of the alerting reaction has never been assessed in the general population. We evaluated the association between the alerting reaction and left ventricular mass by MRI and urinary albumin-to-creatinine ratio in the Dallas Heart Study, a large population sample of 3069 individuals. Participants were categorized into four groups based on levels of consecutive BP: first, normal first BP and average third to fifth (avg3-5) BP of less than 140/90 mmHg (control group); second, high first BP of at least 140/90 mmHg and normal (avg3-5) BP (alerting reaction group); third, normal first BP and high (avg3-5) BP; and fourth, high first to fifth BP. Then, associations between BP categories with incident cardiovascular outcomes (coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death) over a median follow-up period of 9.4 years were assessed. The sample-weighted prevalence of isolated hypertension during the first BP measurement was 9.6%. Presence of an alerting reaction was independently associated with increased left ventricular mass, urinary albumin-to-creatinine ratio, cardiovascular events after adjustment for traditional cardiovascular risk factors, and baseline BP (adjusted hazard ratio 1.24, 95% confidence interval 1.07-1.43). Our study indicated that the alerting reaction is independently associated with increased cardiovascular and renal complications.

Target Organ Complications and Cardiovascular Events Associated With Masked Hypertension and White-Coat Hypertension: Analysis From the Dallas Heart Study

BackgroundMultiple epidemiological studies from Europe and Asia have demonstrated increased cardiovascular risks associated with isolated elevation of home blood pressure (BP) or masked hypertension (MH). Previous studies have not addressed cardiovascular outcomes associated with MH and white-coat hypertension (WCH) in the general population in the United States. ObjectivesThe goal of this study was to determine hypertensive target organ damage and adverse cardiovascular outcomes associated with WCH (high clinic BP, ≥140/90 mm Hg; normal home BP, <135/85 mm Hg), MH (high home BP, ≥135/85 mm Hg; normal clinic BP, <140/90 mm Hg), and sustained hypertension (high home and clinic BP) in the DHS (Dallas Heart Study), a large, multiethnic, probability-based population cohort. MethodsAssociations among WCH, MH, sustained hypertension, and aortic pulsed wave velocity by magnetic resonance imaging; urinary albumin-to-creatinine ratio; and cystatin C were evaluated at study baseline. Then, associations between WCH and MH with incident cardiovascular outcomes (coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death) over a median follow-up period of 9 years were assessed. ResultsThe study cohort comprised 3,027 subjects (50% African Americans). The sample-weighted prevalence rates of WCH and MH were 3.3% and 17.8%, respectively. Both WCH and MH were independently associated with increased aortic pulsed wave velocity, cystatin C, and urinary albumin-to-creatinine ratio. Both WCH (adjusted hazard ratio: 2.09; 95% confidence interval: 1.05 to 4.15) and MH (adjusted hazard ratio: 2.03; 95% confidence interval: 1.36 to 3.03) were independently associated with higher cardiovascular events compared with the normotensive group, even after adjustment for traditional cardiovascular risk factors. ConclusionsIn a multiethnic U.S. population, both WCH and MH were independently associated with increased aortic stiffness, renal injury, and incident cardiovascular events. Because MH is common and associated with an adverse cardiovascular profile, home BP monitoring should be routinely performed among U.S. adults.

Baseline characteristics of African Americans in the Systolic Blood Pressure Intervention Trial

The Systolic Blood Pressure Intervention Trial (SPRINT) will compare treatment to a systolic blood pressure goal of <120 mm Hg to treatment to the currently recommended goal of <140 mm Hg for effects on incident cardiovascular, renal, and neurologic outcomes including cognitive decline. The objectives of this analysis are to compare baseline characteristics of African American (AA) and non-AA SPRINT participants and explore factors associated with uncontrolled blood pressure (BP) by race. SPRINT enrolled 9361 hypertensive participants aged older than 50 years. This cross-sectional analysis examines sociodemographics, baseline characteristics, and study measures among AAs compared with non-AAs. AAs made up 31% of participants. AAs (compared with non-AAs) were younger and less frequently male, had less education, and were more likely uninsured or covered by Medicaid. In addition, AAs scored lower on the cognitive screening test when compared with non-AAs. Multivariate logistic regression analysis found BP control rates to <140/90 mm Hg were higher for AAs who were male, had higher number of chronic diseases, were on diuretic treatment, and had better medication adherence. SPRINT is well poised to examine the effects of systolic blood pressure targets on clinical outcomes as well as predictors influencing BP control in AAs.

Is Sickle Cell Trait Associated with Incident Cardiovascular Outcomes in African Americans?

BackgroundAfrican Americans experience higher rates of cardiovascular disease (CVD) and mortality from stroke and coronary heart disease. It is possible that genetic modifiers associated with African ancestry may confer higher risk of CVD. The sickle cell mutation results from a functional single nucleotide polymorphism (SNP) involving the substitution of GTG (valine) for a GAG (glutamic acid) in the gene encoding beta globin. Heterozygosity for the mutation (rs334) results in sickle cell trait (SCT) which is prevalent among 8% of African Americans, while homozygosity produces sickle cell anemia. Sickle cell trait has been deemed clinically benign yet recent evidence shows that it is associated with increased risk of chronic kidney disease, a 2 times increased risk for venous thromboembolism and a 4 times increased risk for pulmonary embolism. Further, there is evidence that individuals with SCT have higher serum levels of C-reactive protein, Fibrinogen 2.1 fragments and D-dimers. We hypothesized that African Americans with SCT have a higher risk for cardiovascular outcomes than those without SCT (homozygous wild-type hemoglobin).MethodsData were obtained from the Multi-Ethnic Study of Atherosclerosis (MESA), Jackson Heart Study (JHS) and Women’s Health Initiative (WHI). Incident myocardial infarction (MI) was defined as adjudicated non-fatal or fatal MI, coronary heart disease (CHD) was defined as a composite endpoint including adjudicated non-fatal MI, fatal CHD, or documented coronary revascularization procedure. Sickle cell trait was identified either by direct genotyping or imputation for rs334. Individuals who were homozygous for the sickle mutation or had a prior history of CHD events were excluded. Cox proportional hazards models were used to estimate a hazard ratio (HR) of incident MI or CHD comparing sickle cell trait carriers to non-carriers. Models were adjusted for age, sex and principal component of global ancestry. Analysis was performed separately in each cohort and the results were subsequently meta-analyzed using a fixed effect inverse variance weighted method.ResultsA total of 11,128 African American men and women were included in the pooled data base. The average age at baseline were 62.2 ± 10.1, 49.8 ± 11.8 and 61.4 ± 7.0 years for MESA, JHS and WHI respectively, with JHS participants significantly younger than the other two cohorts (p <0.001). Unlike the MESA and JHS cohorts that included both genders, the WHI cohort was exclusively female. Additionally, the percentage African ancestry was significantly higher among those with SCT compared to those without SCT (82 ± 12% vs. 78 ± 14% for MESA, 84 ± 6% vs. 82 ± 9% for JHS and 79 ± 12% vs. 76 ± 15% for WHI), further the percentage African ancestry was significantly lower among WHI subjects irrespective of carrier status, p <0.01. There was no significant difference between cohorts in the prevalence of diabetes or hypertension, mean blood pressure levels, or proportion of smokers (table 1). The HR for incident MI was 1.56 (0.66 – 3.68) in MESA, 1.04 (0.32 – 3.39) in JHS and 0.97 (0.68 – 1.39) in WHI, but was not statistically significant. Further, the HR for incident CHD was 2.73 (1.52 – 4.89) in MESA, 1.14 (0.46 – 2.89) in JHS and 0.97 (0.68 – 1.17) in WHI, although the HR only achieved statistical significance in MESA (p<0.001). Overall, sickle cell trait was not significantly associated with incident MI (1.04 [0.76 – 1.43]) or CHD (1.11 [0.85 – 1.43] figure 1).Limitation/Recommendations and ConclusionThe overall result from this study did not demonstrate a significant association between SCT and CHD. This may reflect inadequate power due to the relatively small number of CHD events and differences in study design. This study suggests the need for a well powered study to test this hypothesis, the result of which could have significant impact on the approach to risk factor modification for African Americans. [Display omitted] [Display omitted] DisclosuresNaik:NHLBI: Research Funding.

Biomarkers of cardiovascular stress and subclinical atherosclerosis in the community.

Biomarkers of cardiovascular stress have been associated with incident cardiovascular outcomes. Their relations with measures of subclinical atherosclerosis, as assessed by carotid intima-media thickness, have not been well described. We measured plasma growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) in 3111 Framingham Offspring participants who also underwent carotid ultrasonography during the sixth examination (1995-1998, mean age 58 years, 54% women). Carotid measurements included maximal internal carotid artery (ICA) intima-media thickness (IMT), plaque presence (defined as ICA IMT >1.5 mm), and mean common carotid artery IMT. We carried out multivariable regressions for carotid measurements vs biomarkers using linear and logistic models; P < 0.0056 was deemed statistically significant. Maximal ICA IMT was significantly associated with plasma GDF-15 [β-estimate 0.04 per 1-U increase in log(GDF-15), SE 0.01, P < 0.0001]. Similarly, the odds of having carotid plaque increased 33% [odds ratio 1.33 per 1-U increase in log(GDF-15), 95% CI 1.20-1.48, P < 0.0001]. In contrast, there was no significant association of maximal ICA IMT or plaque presence with sST2 or hsTnI, and none of the 3 biomarkers was significantly associated with mean CCA IMT. GDF-15 was a stronger predictor of maximal ICA thickness and plaque presence compared with BNP and CRP when these conventional biomarkers were tested together. Increased GDF-15 concentrations are associated with subclinical atherosclerosis, including maximal ICA IMT and carotid plaque presence. Future studies investigating the role of GDF-15 for screening and management of patients with subclinical atherosclerosis are warranted.

Cardiovascular and neuropsychiatric safety of varenicline and bupropion compared with nicotine replacement therapy for smoking cessation: study protocol of a retrospective cohort study using the QResearch general practice database

IntroductionCigarette smoking continues to be the leading cause of preventable death and is the main risk factor of major diseases such as chronic obstructive pulmonary disease (COPD). The best treatment...

Parathyroid hormone concentration and risk of cardiovascular diseases: The Atherosclerosis Risk in Communities (ARIC) study

According to a recent meta-analysis, parathyroid hormone (PTH) excess is associated with increased cardiovascular disease (CVD) risk, but existing studies are limited. We examined in a prospective study the association of PTH with the incidence of CVD, taking into account vitamin D and other confounding variables. The ARIC study measured PTH using a second-generation assay (Roche, Indianapolis, IN) in stored serum samples from 1990 to 1992 and related levels in 10,392 adults to incident cardiovascular outcomes (coronary heart disease [n = 808], heart failure [n = 1,294], stroke [n = 586], peripheral artery disease [n = 873], atrial fibrillation [n = 1,190], and CVD mortality [n = 647]) through 2010 (median follow-up 19 years). Contrary to the hypothesis, PTH level was not associated positively with any CVD outcome. The associations of incident heart failure, peripheral artery disease, and CVD mortality with PTH actually were weakly inverse (P trend = .02-.04) in the most fully adjusted models. For example, the hazard ratios across PTH quartiles were 1.00, 1.07, 1.07, and 0.96 (P trend = .74) for coronary heart disease incidence and were 1.00, 0.69, 0.74, and 0.74 (P trend = .02) for CVD mortality. Patterns were similar when restricted to participants with normal baseline kidney function. This large prospective study failed to support the hypothesis that elevated PTH is an independent risk marker for incident CVD. When our data were added to the previous meta-analysis, the pooled hazard ratio remained statistically significant but weakened.

Predictive value of midregional pro-adrenomedullin compared to natriuretic peptides for incident cardiovascular disease and heart failure in the population-based FINRISK 1997 cohort

Introduction. To examine whether midregional pro-adrenomedullin (MR-proADM) plasma concentrations predict incident cardiovascular outcomes in the general population. Natriuretic peptides (N-terminal pro-brain natriuretic peptide (NT-proBNP), B-type natriuretic peptide (BNP), and midregional pro-atrial natriuretic peptide (MR-proANP)) were analyzed for comparison.Material and methods. MR-proADM plasma concentrations and those of the natriuretic peptides were determined in 8444 individuals of the FINRISK 1997 cohort. Patients were followed for 14 years (median). Cox regression analyses, discrimination, and reclassification analyses adjusting for Framingham risk factors were performed to evaluate the additional benefit from MR-proADM.Results. MR-proADM concentrations significantly predicted all-cause death (hazard ratio highest quintile versus lowest 1.18, 95% confidence interval 1.08–1.28), stroke (1.20, 1.05–1.38), major adverse cardiac events (MACE) (1.27, 1.17–1.37), and heart failure (1.67, 1.49–1.87). MR-proADM remained associated with MACE, death, and heart failure even after additional adjustment for NT-proBNP and C-reactive protein. Adding MR-proADM to the Framingham risk factors significantly improved discrimination (P < 0.001 for C-statistics and integrated discrimination improvement) and risk reclassification for heart failure (net reclassification improvement 12.12%, P < 0.001).Conclusions. In a healthy general population sample of the FINRISK 1997 cohort MR-proADM significantly predicted all-cause death, MACE, and especially heart failure even beyond NT- proBNP. It also improved risk reclassification for heart failure.

Analysis of a Urinary Biomarker Panel for Incident Kidney Disease and Clinical Outcomes

Whether novel biomarkers improve the assessment of incident kidney disease and related adverse outcomes remains to be tested in longitudinal observational studies. We tested 14 urinary biomarkers for association with incident kidney, cardiovascular, and mortality outcomes in 2948 Framingham Heart Study participants. Baseline examinations were performed between 1995 and 1998; mean follow-up was 10.1 years for renal outcomes and 11.2 years for survival analyses. Primary outcomes were incident CKD, incident albuminuria, incident cardiovascular disease, and all-cause mortality. Secondary analyses assessed incident congestive heart failure (CHF) and mortality with coexistent kidney disease. Biomarkers were tested for association with renal end points using logistic regression and incident cardiovascular and mortality outcomes in proportional hazards models; α1-microglobulin, Kim-1, and TFF-3 predicted all-cause mortality (hazard ratio per SD increase in log-transformed biomarker [HR] range, 1.15 to 1.21; 95% confidence interval [CI] range, 1.04 to 1.34; P values=0.007 to <0.001), whereas α1-microglobulin, β2-microglobulin, KIM-1, and TFF-3 associated with death with coexistent kidney disease (HR range, 1.72-2.25; 95% CI, 1.17 to 3.24; P values<0.01). KIM-1 also associated with the risk of incident CHF (HR, 1.32; 95% CI, 1.07 to 1.63; P=0.008). CTGF associated nominally with CKD (HR, 0.83; 95% CI, 0.71 to 0.98; P=0.03), but no other biomarkers associated with incident CKD or albuminuria. Addition of α1-microglobulin and TFF-3 resulted in a nonsignificant net reclassification index (NRI) of 3% for all-cause mortality beyond clinical risk factors. In conclusion, components of a panel of 14 subclinical biomarkers of kidney injury were associated with important clinical outcomes and merit additional investigation.

The Association of Plasma Lactate With Incident Cardiovascular Outcomes

We examined the association of plasma lactate at rest, a marker of oxidative capacity, with incident cardiovascular outcomes in 10,006 participants in the Atherosclerosis Risk in Communities (ARIC) Study visit 4 (1996-1998). We used Cox proportional-hazards models to estimate hazard ratios of incident coronary heart disease, stroke, heart failure, and all-cause mortality by quartiles of plasma lactate (Q1, ≤5.3 mg/dL; Q2, 5.4-6.6; Q3, 6.7-8.6; and Q4 ≥8.7). During a median follow-up time of 10.7 years, there were 1,105 coronary heart disease cases, 379 stroke cases, 820 heart failure cases, and 1,408 deaths. A significant graded relation between lactate level and cardiovascular events was observed in the demographically adjusted model (all P for trend< 0.001). After further adjustment for traditional and other potential confounders, the association remained significant for heart failure (Q4 vs. Q1: hazard ratio (HR)= 1.35, 95% confidence interval (CI): 1.07, 1.71) and all-cause mortality (HR= 1.27, 95% CI: 1.07, 1.51) (P for trend< 0.02 for these outcomes) but not for coronary heart disease (HR= 1.02, 95% CI: 0.84, 1.24) and stroke (HR= 1.26, 95% CI: 0.91, 1.75). The results for heart failure were robust across multiple subgroups, after further adjustment for N-terminal pro-B-type natriuretic peptide and after exclusion of participants with incident heart failure within 3 years. The independent associations of plasma lactate with heart failure and all-cause mortality suggest an important role for low resting oxidative capacity.

Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia

BackgroundThe provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested.MethodsWe randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n–3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups.ResultsThe median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97).ConclusionsWhen used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.)

Do microvascular retinal changes improve cardiovascular risk estimation?

Do microvascular retinal changes improve cardiovascular risk estimation?

Associations between vitamin D and cardiovascular outcomes; Tehran Lipid and Glucose Study

BackgroundVitamin D status seems to have an association with cardiometabolic risk factors and its deficiency may negatively affect the cardiovascular outcomes. The aim of this study was to determine the possible association between vitamin D status and cardiovascular outcomes. MethodWe performed a nested case control study within the Tehran Lipid and Glucose Study (TLGS), which followed a representative sample of Tehranian adults. A total of 251 matched pairs, aged>30 years, were selected. Cases were TLGS individuals that were free of cardiovascular disease (CVD) at the beginning of study and developed CVD during assessments of 5.7 year follow up. Each case was matched by age, sex and the month of entry to study with a randomly selected control (risk-set sampling). Prespecified cut points were used to characterize varying degrees of 25-OH D deficiency (<10, between 10 and 14.9, and ≥15ng/ml). Conditional logistic regression was used to investigate the association between 25-OH-D concentration and the incident cardiovascular outcomes. ResultsThe mean age of participants was 56.84±11.17 years and 244 (48.6%) were women. The median (IQ: 25–75) of serum 25-OH-D was 14.1ng/ml (9.6–29ng/ml) and 306 (61%) of participants had serum 25-OH-D<15g/ml. Median serum 25-OH-D was lower in cases (12.5 vs. 18.1, P<0.001). After adjustment for potential confounders, the odds ratio of serum 25-OH-D<10ng/ml for having CVD outcomes was 2.90 compared with 25-OH-D≥15 (95% confidence interval (CI): 1.67–5.12, P<0.001). ConclusionOur results indicate that serum 25-OH-D concentration has an independent association with cardiovascular outcomes in adult Tehranians.

Cystatin C: a step forward in assessing kidney function and cardiovascular risk

The cardiorenal syndrome is a clinical manifestation of the bidirectional interaction between the heart and kidneys. Evaluating renal function is an essential part of the assessment of every cardiac patient. It has become clear that serum creatinine is not an accurate enough marker of glomerular filtration rate (GFR) and should not be used to evaluate kidney dysfunction. Creatinine-based estimates of GFR are preferred, but require renal function to be stable and are not suitable when changes in kidney function occur. Cystatin C (CysC) has been the target of much interest in the search for an alternative measure of GFR. As an endogenous biomarker, CysC possesses many of the properties required of a good marker of renal function. Compared with that of creatinine, plasma concentrations of CysC are less influenced by factors other than GFR. Consequently, CysC correlates with true GFR more accurately than creatinine. Equations for estimating GFR from CysC values have also been developed, which makes values easier to interpret and facilitates the clinical use of this new marker. The use of CysC in acute kidney injury has also shown promising results. CysC has been studied as a risk marker for prognosis in cardiovascular disease. This effect is attributed to the strong impact of renal dysfunction on progressive cardiovascular disease and impaired survival. Higher levels of CysC have consistently been predictive of incident or recurrent cardiovascular events and adverse outcomes. CysC is a predictor of the development of heart failure and increased levels of CysC have an independent association with higher mortality in both chronic and acute heart failure. In conclusion, CysC appears to be an interesting marker of renal function and is useful for risk stratification in heart failure.

Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies

SummaryBackgroundGuidelines differ about the value of assessment of adiposity measures for cardiovascular disease risk prediction when information is available for other risk factors. We studied the separate and combined associations of body-mass index (BMI), waist circumference, and waist-to-hip ratio with risk of first-onset cardiovascular disease.MethodsWe used individual records from 58 cohorts to calculate hazard ratios (HRs) per 1 SD higher baseline values (4·56 kg/m2 higher BMI, 12·6 cm higher waist circumference, and 0·083 higher waist-to-hip ratio) and measures of risk discrimination and reclassification. Serial adiposity assessments were used to calculate regression dilution ratios.ResultsIndividual records were available for 221 934 people in 17 countries (14 297 incident cardiovascular disease outcomes; 1·87 million person-years at risk). Serial adiposity assessments were made in up to 63 821 people (mean interval 5·7 years [SD 3·9]). In people with BMI of 20 kg/m2 or higher, HRs for cardiovascular disease were 1·23 (95% CI 1·17–1·29) with BMI, 1·27 (1·20–1·33) with waist circumference, and 1·25 (1·19–1·31) with waist-to-hip ratio, after adjustment for age, sex, and smoking status. After further adjustment for baseline systolic blood pressure, history of diabetes, and total and HDL cholesterol, corresponding HRs were 1·07 (1·03–1·11) with BMI, 1·10 (1·05–1·14) with waist circumference, and 1·12 (1·08–1·15) with waist-to-hip ratio. Addition of information on BMI, waist circumference, or waist-to-hip ratio to a cardiovascular disease risk prediction model containing conventional risk factors did not importantly improve risk discrimination (C-index changes of −0·0001, −0·0001, and 0·0008, respectively), nor classification of participants to categories of predicted 10-year risk (net reclassification improvement −0·19%, −0·05%, and −0·05%, respectively). Findings were similar when adiposity measures were considered in combination. Reproducibility was greater for BMI (regression dilution ratio 0·95, 95% CI 0·93–0·97) than for waist circumference (0·86, 0·83–0·89) or waist-to-hip ratio (0·63, 0·57–0·70).InterpretationBMI, waist circumference, and waist-to-hip ratio, whether assessed singly or in combination, do not importantly improve cardiovascular disease risk prediction in people in developed countries when additional information is available for systolic blood pressure, history of diabetes, and lipids.FundingBritish Heart Foundation and UK Medical Research Council.

Are Renin-Angiotensin-Aldosterone System Blockers Distinguishable Based on Cardiovascular and Renal Outcomes in Nephropathy?

Drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) are the cornerstone of therapy for cardiovascular and renal disease because they protect against worsening outcomes in the respective target organs. Recent results from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) have confirmed that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) confer similar cardioprotection and renoprotection, showing little to no benefit from the combination in cardiovascular disease. It is not yet clear whether one class is superior to another for renoprotection. Whether dual RAAS blockade is more advantageous than single blockade, and in which patients, is also yet to be clearly determined. The Long-Term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) study will compare the cardiorenoprotective effects of ACE inhibitors and ARBs in patients with albuminuria, and clarify the role of dual blockade. Preliminary evidence that RAAS inhibitors reduce incident diabetes is intriguing. Whether ARBs can reduce incident diabetes and related cardiovascular outcomes is awaited with the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.

Non-traditional risk factors predict coronary calcification in chronic kidney disease in a population-based cohort

The increased burden of cardiovascular disease in chronic kidney disease cannot be explained by traditional risk factors alone. Here, we evaluated the impact of non-traditional factors on the association of chronic kidney disease with coronary artery calcification using logistic regression among 2672 Dallas Heart Study patients of whom 220 had chronic kidney disease. The prevalence of coronary calcification significantly increased across all chronic kidney disease stages and this remained independently associated with coronary calcification after adjusting for traditional factors. The calcium x phosphorus product, homocysteine, and osteoprotegerin each diminished the magnitude of association between kidney disease and coronary calcification. After adjustment for these, the association between kidney disease and coronary calcification was no longer significant with the effects most prominent in the stages 3-5 subgroup. Our study has identified three non-traditional independent predictors of coronary calcification that diminished the association between chronic kidney disease and coronary calcification. These factors may represent novel mechanistic links warranting further investigation.