Intensive versus conventional glucose control in critically ill patients: A meta-analysis of randomized controlled trials

BackgroundCritically ill patients commonly develop hyperglycemia. It remains unclear, however, to what extent correcting hyperglycemia will benefit these patients. We performed this meta-analysis to evaluate the benefits and risks of intensive glucose control versus conventional glucose control in critically ill adult patients.MethodsA systematic literature search of MEDLINE, PubMed, and Cochrane databases (until June 2011) was conducted using specific search terms. Randomized controlled trials that compared intensive glucose control with a target glucose goal < 6.1 mmol/l (110 mg/dl) to conventional glucose control in adult intensive care patients were included. The random-effect model was used to estimate the pooled risk ratio of the two treatment arms.ResultsTwenty two studies that randomized 13,978 participants were included in the meta-analysis. Overall, intensive glucose control did not reduce the short-term mortality (RR = 1.02, 95% CI: 0.95–1.10, p = 0.51), 90 day or 180 day mortality (RR = 1.06, 95% CI: 0.99–1.13, p = 0.08), sepsis (RR = 0.96, 95% CI: 0.83–1.12, p = 0.59) or new need for dialysis (RR = 0.96, 95% CI: 0.83–1.11, p = 0.57). The incidence of hypoglycemia was significantly higher in intensive glucose control group compared with conventional glucose control group (RR = 5.01, 95% CI: 3.45–7.28, p < 0.00001).ConclusionsThis meta-analysis found that intensive glucose control in critically ill adults did not reduce mortality but is associated with a significantly increased risk of hypoglycemia.     

The degree of retinopathy is equally predictive for renal and macrovascular outcomes in the ACCORD Trial

AimsDiabetic retinopathy (DR) is associated with a higher risk of renal and cardiovascular events. We sought to compare the risk for renal versus cardiovascular (CV) outcomes, stratified by retinopathy severity.MethodsACCORD was a randomized trial of people with type 2 diabetes, at high-risk for CV disease. A subgroup (n = 3,369 from 71 clinics) had stereoscopic fundus photographs graded centrally. Participants were stratified at baseline to moderate/severe DR or no/mild DR and were monitored for renal and CV outcomes at follow-up visits over 4 years. The composite renal outcome was composed of serum creatinine doubling, macroalbuminuria, or end-stage renal disease. The composite CV outcome was the ACCORD trial primary outcome. Competing risk techniques were used to estimate the relative risk (RR) of renal versus CV composite outcomes within each DR stratum.ResultsThe hazards ratio for doubling of serum creatinine and incident CV event in the moderate/severe DR versus no/mild DR strata were: 2.31 (95% CI: 1.25–4.26) and 1.98 (95% CI: 1.49–2.62), respectively. The RR of the two composite outcomes was highly similar in the no/mild DR stratum (adjusted RR at 4 years for CV versus renal events = 0.96, 95% CI: 0.72–1.28) and the moderate/severe DR stratum (adjusted RR = 0.92, 95% CI: 0.64–1.31).ConclusionsThus, in people with type 2 diabetes at high risk for cardiovascular disease, incident CV versus renal events was similar, irrespective of the severity of the DR. Further evaluation of the specificity of DR for microvascular versus macrovascular events in other populations is warranted.     

The metabolic syndrome in early pregnancy and risk of gestational diabetes mellitus

AimThe objective of the present study was to determine whether or not maternal metabolic syndrome in early pregnancy in women without previous diabetes is associated with the development of gestational diabetes mellitus (GDM).MethodsA total of 508 women from the Rhea study—involving a pregnant cohort in Crete, Greece (2007–2009)—with singleton pregnancies were included in the present analysis. Maternal fasting serum samples were collected and blood pressure measured before gestational week 15. The metabolic syndrome in early pregnancy was defined according to NHLBI/AHA criteria. Pregnant women were screened for GDM between weeks 24 and 28 of gestation, as defined by Carpenter and Coustan criteria. Multivariable log-binomial regression models were used to estimate the effect of the metabolic syndrome in early pregnancy on the risk of GDM, after adjusting for confounding factors.ResultsWomen with the metabolic syndrome were at high risk of GDM (RR = 3.17; 95% CI: 1.06–9.50). Among the components of the metabolic syndrome, the most significant risk factors were impaired fasting glucose (RR = 4.92; 95% CI: 1.41–17.23) and pre-pregnancy obesity (RR = 2.65; 95% CI: 1.23–5.70). A 10-mmHg rise in systolic and diastolic blood pressure increased the relative risk of GDM by 49% (RR = 1.49; 95% CI: 1.10–2.02) and 34% (RR = 1.34; 95% CI: 1.04–1.73), respectively, whereas a 1-unit increase in pre-pregnancy BMI increased the relative risk of GDM by 6% (RR = 1.06; 95% CI: 1.01–1.12).ConclusionThese findings suggest that women with the metabolic syndrome in early pregnancy have a greater risk of developing GDM.     

Modifiable risk factors for nursing home admission among individuals with high and low dementia risk

BackgroundStrategies to prevent or delay nursing home admission in individuals with cognitive impairment are urgently needed. We hypothesized that physical inactivity, not consuming alcohol (as opposed to moderate alcohol use), and having a history of smoking predict nursing home admission among individuals with normal cognitive function, but these behavioral factors would have attenuated associations with nursing home admission among individuals with impaired cognition.MethodsWe performed a prospective cohort study among 7631 Health and Retirement Study participants aged 65+ at baseline. Baseline dementia risk (high versus low, based on brief psychometric assessments and proxy reports) and modifiable risk factors (physical inactivity, ever smoking, and not consuming alcohol) were used to predict nursing home admission in pooled logistic regression models. We evaluated whether estimated effects of modifiable factors varied by dementia risk, comparing both relative and absolute effects using interaction terms between dementia risk and each modifiable risk factor.ResultsLow dementia probability was associated with lower nursing home admission risk (RR = 0.49; 95% CI: 0.41, 0.59). Physical inactivity (RR = 1.27; 95% CI: 1.15, 1.41), ever smoking (RR = 1.12; 95% CI: 1.01, 1.25), and not consuming alcohol (RR = 1.28; 95% CI: 1.13, 1.45) predicted increased relative risk of nursing home admission regardless of cognitive status. The relative effects of modifiable risk factors were similar for those with low and high dementia risk.ConclusionAlthough cognitive impairment associated with incipient dementia strongly predicts nursing home admission, this risk can be partially ameliorated with modifiable risk factors such as physical activity.     

Dietary fat, abdominal obesity and smoking modulate the relationship between plasma complement component 3 concentrations and metabolic syndrome risk

ObjectiveChronic inflammation plays a role in the pathogenesis of metabolic syndrome (MetS) and cardiovascular disease (CVD). Complement component 3 (C3) is a novel cardiometabolic risk factor. Whether dietary fat intake modulates MetS risk conferred by elevated C3 concentrations is unknown. Our objective is to investigate the relationship between C3 concentrations and risk of the MetS and its phenotypes, and to further examine whether dietary fat intake modulates these relationships.MethodsBiochemical, dietary and lifestyle measurements were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754).ResultsElevated C3 concentrations (>median) were associated with increased risk of impaired insulin sensitivity [OR 1.78, CI 1.34–2.36, P < 0.0001], insulin resistance [OR 1.73, CI 1.31–2.89, P = 0.0001], abdominal obesity [OR 2.15, CI 1.43–3.24, P = 0.0002] and low HDL cholesterol [OR 1.40, CI 1.05–1.86, P = 0.02] compared to low C3 concentrations. Increased MetS risk conferred by elevated C3 concentrations [OR 3.11, 95% CI 2.52–3.82, P < 0.0001] was further accentuated among high dietary fat consumers [OR 4.80, 95% CI 2.77–8.33, P < 0.0001] (particularly of saturated [OR 4.05, 95% CI 2.33–7.05, P < 0.0001] and monounsaturated fat [OR 4.48, 95% CI 2.62–7.56, P < 0.0001]), and smokers [OR 3.83, 95% CI 2.12–6.94, P < 0.0001], however this effect was abolished in abdominally lean individuals [OR 1.46, 95% CI 0.69–3.14, P = 0.33].ConclusionsDietary fat (intake and composition), abdominal obesity and smoking modulate the relationship between elevated plasma C3 concentrations and MetS risk.     

Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: data from the Heart and Soul Study

ObjectiveSerum adiponectin protects against incident ischemic heart disease (IHD). However, in patients with existing IHD, higher adiponectin levels are paradoxically associated with worse outcomes. We investigated this paradox by evaluating the relationship between adiponectin and cardiovascular events in patients with existing IHD.MethodsWe measured total serum adiponectin and cardiac disease severity by stress echocardiography in 981 outpatients with stable IHD who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent heart failure hospitalizations, myocardial infarction, and death were recorded.ResultsDuring an average of 7.1 years of follow-up, patients with adiponectin levels in the highest quartile were more likely than those in the lowest quartile to be hospitalized for heart failure (23% vs. 13%; demographics-adjusted hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.04–2.56, p = 0.03) or die (49% vs. 31%; HR 1.67, 95% CI 1.24–2.26, p < 0.008), but not more likely to have a myocardial infarction (12% vs. 17%; HR 0.64, 95% CI 0.38–1.06, p = 0.08). The combined outcome of myocardial infarction, heart failure, or death occurred in 56% (136/245) of participants in the highest quartile of adiponectin vs. 38% (94/246) of participants in the lowest quartile (HR 1.54, 95% CI 1.31–2.21, p < 0.002). Adjustment for left ventricular ejection fraction, diastolic dysfunction, inducible ischemia, C-reactive protein, and NT-proBNP attenuated the association between higher adiponectin and increased risk of subsequent events (HR 1.43, 95% CI 0.98–2.09, p = 0.06).ConclusionsHigher concentrations of adiponectin were associated with heart failure and mortality among patients with existing IHD.     

Prediction of cardiovascular events, diabetic nephropathy, and mortality by albumin concentration in a spot urine sample in patients with type 2 diabetes

AimsTo analyze in a random urine spot the predictive value of urinary albumin concentration (UAC) for cardiovascular events, diabetic nephropathy (DN), and death in patients with type 2 diabetes.MethodsIn this cohort, urinary albumin (immunoturbidimetry) was measured as 24-h urinary albumin excretion (UAE) and, in a random spot urine, as UAC and albumin:creatinine ratio (ACR). Primary outcomes were: 1) cardiovascular events, 2) DN defined as a composite outcome [macroalbuminuria and/or decreased glomerular filtration rate (GFR) < 60 ml/min/1.73 m²], and 3) death.ResultsA total of 199 type 2 diabetic patients, aged 59.9 ± 9.9 years, were followed for 6.1 ± 2.7 years. UAC ≥ 14.4 mg/l, as determined by ROC curve, predicted DN and prediction for this and other outcomes were compared with traditional microalbuminuria cutoffs for ACR and UAE. The outcomes frequency was: cardiovascular events = 26.4%, DN = 31.7% (23.5% decreased GFR; 13.6% macroalbuminuria) and death = 8.50%. In Cox analyses, UAC ≥ 14 mg/l increased the risk (hazard ratio, HR) for cardiovascular events 3.25 times (95% CI 1.43–7.38; P = 0.005), 4.30 for DN composite outcome (95% CI 2.22–8.32; P < 0.001), and 5.51 for death (95% CI 1.16–26.22; P = 0.032). Corresponding HRs of ACR ≥ 30 mg/g were: 2.89 (95% CI 1.29–6.45; P = 0.009) for cardiovascular events, 4.67 (95% CI 2.34–9.34; P < 0.001) for DN composite outcome and 5.07 (95% CI 1.01–24.88; P = 0.049) for death. HRs of UAE ≥ 30 mg/24-h were: 2.20 (95% CI 2.08–2.49; P = 0.030) for cardiovascular events, 6.76 (95% CI 3.32–13.77; P < 0.001) for DN composite outcome, and 2.47 (95% CI 0.72–8.42; P = 0.150) for death.ConclusionsIn conclusion, random UAC ≥ 14 mg/l predicted cardiovascular events, diabetic nephropathy, and mortality just as well as ACR. UAC may be used to assess cardiovascular and renal risks in patients with type 2 diabetes.     

Diagnostic and prognostic value of procalcitonin in community-acquired pneumonia

IntroductionThe value of measuring procalcitonin (PCT) in patients with community-acquired pneumonia (CAP) is unclear. The aim of this study was to determine the value of PCT as a marker for microbial etiology and a predictor of outcome in CAP patients.MethodsA single-center observational study was conducted with CAP patients. On admission, their leukocyte count, serum C-reactive protein level, and serum PCT level were determined, and microbiological tests were performed. Patients were classified into 4 groups according to the A-DROP scoring system, which assesses the severity of CAP.ResultsA total of 102 patients were enrolled. The pathogen was identified in 60 patients, and 31 patients had streptococcal pneumonia. The PCT levels were significantly higher in those patients with pneumococcal pneumonia than in those patients with other bacterial pneumonias (P < 0.0001). Multivariate regression analysis revealed that high PCT levels were associated with a pneumococcal etiology [odds ratio, 1.68; 95% confidence interval (CI): 1.02–2.81; P = 0.04] after adjustment for disease severity and demographic factors. The PCT levels were correlated with the A-DROP score (r = 0.49; P < 0.0001). The area under the curve for predicting mortality was highest for the A-DROP score (0.97; 95% CI: 0.92–0.99), followed by the area under the curve for PCT (0.82; 95% CI: 0.74–0.89) and C-reactive protein (0.77; 95% CI: 0.67–0.84).ConclusionsHigh PCT levels indicate that pneumococcal pneumonia and PCT levels depend on the severity of pneumonia. PCT measurements may provide important diagnostic and prognostic information for patients with CAP.     

Telomerase, telomere length, and coronary artery calcium in black and white men in the CARDIA study

ObjectiveTo evaluate whether telomerase activity, measured in circulating blood leukocytes, might be associated with prevalent atherosclerosis, or predict future coronary artery disease risk.Methods and resultsWe examined associations of telomerase activity levels measured at year 15 in the Coronary Artery Risk Development in Young Adults (CARDIA) Study with prevalent coronary artery calcium (CAC), progressive CAC at year 20, and incident CAC between years 15 and 20, in 440 black and white men aged 33–45 years. Telomere length was also measured in a subset of participants (N = 129).In multivariate-adjusted analysis, higher quartiles of telomerase were cross-sectionally associated with greater odds of prevalent CAC at year 15 (quartile 2: OR = 1.32, 95% CI: 0.54–3.23; quartile 3: OR = 1.40, 95% CI: 0.60–3.30; quartile 4: OR = 3.27, 95% CI: 1.39–7.71 compared with quartile 1, p-continuous = 0.012) and progressive CAC at year 20, but telomerase was not significantly associated with incidence of newly detectable CAC. Higher telomerase activity levels predicted greater CAC progression at year 20 among persons with short telomere length; low telomerase and short TL predicted less CAC progression.ConclusionTelomerase activity in leukocytes was associated with calcified atherosclerotic plaque, and was also a predictor of advancing plaque among persons with short telomeres.     

Components of metabolic syndrome and the incidence of type 2 diabetes in an elderly Taiwanese cohort

AimsMetabolic syndrome (MetS) is at great risk of developing type 2 diabetes (T2DM). This study aimed to explore the association between the major MetS components and the T2DM incidence in an elderly Taiwanese population.Methods1738 subjects, aged 65–84 years, were enrolled from the Taiwan MJ health check-up in 2000 and 2001 and were again investigated in 2005 and 2006. Factor analysis was conducted and factor scores for the baseline of non-diabetic individuals were used as independent variables in logistic regression models to determine risk factors predicting the development of diabetes.ResultsMetS was common among the elderly residents receiving long-term health check-up in Taiwan. Sex-specific factor analyses yielded five separate factors including obesity, etc., accounting for 65.9% and 65.3% of the total variance in non-diabetic men and women, respectively. There were 56 males (6.44%) and 44 females (6.32%) without diabetic at baseline, developed diabetes during the mean 4.95 years follow-up. For non-diabetic men, blood lipids/FPG was strongly associated with diabetes incidence (RR = 2.22, 95% CI 1.69–2.92), while for women, FPG/inflammation factor had biggest RR (RR = 1.94, 95% CI 1.47–2.56). Among factor patterns, obesity was major cluster and as the common determinant of the diabetes risk for two sexes (RR = 1.33, 95% CI 1.02–1.73 and RR = 1.72, 95% CI 1.27–2.31, for men and women, respectively), but the BP was not associated with prediction of diabetes both in two genders.ConclusionsIdentification of five unique factors with different associations with incidence of diabetes suggests that the correlations among these variables reflect distinct metabolic processes rather than one single underlying entity in the elderly Taiwan cohort, and that the blood lipids/FPG and FPG/inflammation factor in both sexes predicting progression to T2DM beyond obesity alone.     

Non-linear association between ankle-brachial pressure index and prevalence of silent cerebral infarction in Japanese patients with type 2 diabetes

ObjectivePatients with peripheral artery disease (PAD), defined as having low ankle-brachial pressure index (ABI), have increased risk for incident stroke compared with those without PAD. We aimed to reveal whether ABI abnormality, especially high ABI is associated with prevalent silent cerebral infarction (SCI) in type 2 diabetic patients.MethodsWe studied 538 Japanese type 2 diabetic patients, 227 women and 311 men, with a mean [±SD] age of 64 ± 11 years. All patients underwent cranial magnetic resonance imaging (MRI). Values of ABI were classified as low (<0.9), normal (0.9≤ and <1.3), and high (1.3≤). Logistic regression model was used to calculate odds ratio and 95% confidence interval (95% CI) for prevalent SCI.ResultsThe mean ABI among the overall 538 patients was 1.09 ± 0.16. Low and high ABI values were found in 52 (9.7%) and 33 (6.1%) patients, respectively. SCI was detected in 297 (55.2%) patients. The prevalence in patients with low, normal, and high ABI values were 88.5%, 49.7%, and 78.8 (p < 0.001), respectively. In the multivariate logistic regression analysis, both patients with high and low ABI were significantly increased risk of prevalent SCI (odds ratio 4.53, 95% CI 1.67–12.34, p = 0.003 and odds ratio 3.50, 95% CI 1.50–10.29, p = 0.005), independently of other traditional cardiovascular risk factors, than those with normal ABI.ConclusionsBoth high and low ABI may be strongly associated with prevalent SCI in Japanese patients with type 2 diabetes.     

Association of single measurement of estimated glomerular filtration rate and non-quantitative dipstick proteinuria with all-cause and cardiovascular mortality in the elderly. Results from the Progetto Veneto Anziani (Pro.V.A.) Study

ObjectiveTo explore the independent and combined clinical validity of estimated glomerular filtration rate (eGFR) and proteinuria on predicting all-cause and cardiovascular mortality in an Italian elderly population.MethodsBaseline eGFR and proteinuria, all-cause and cardiovascular mortality during a mean follow-up time of 4.4 years were evaluated in 3063 subjects aged 65 years and older of the Progetto Veneto Anziani (Pro.V.A.) Study.ResultsSubjects with eGFR < 60 ml/min/1.73 m² (n = 956) presented a higher prevalence of proteinuria in comparison with those with eGFR ≥ 60 ml/min/1.73 m² (33.8% vs 25.1%, p < 0.01). After multivariable adjustment including proteinuria and major diseases, eGFR < 60 ml/min/1.73 m² was not associated with increased all-cause mortality. After multivariable adjustment including eGFR and major diseases, proteinuria was associated with all-cause mortality in overall subjects (HR = 1.43, 95% CI 1.15–1.78, p < 0.01), and in both sexes. After multivariable adjustment both eGFR < 60 ml/min/1.73 m² (HR = 1.68, 95% CI 1.02–2.78, p = 0.04), and proteinuria (HR = 2.07, 95% CI 1.31–3.27, p < 0.01) were associated with increased cardiovascular mortality. Subjects with both impaired eGFR and presence of proteinuria showed a higher risk for both all-cause and cardiovascular mortality compared to those with normal eGFR and absence of proteinuria.ConclusionIn this general Italian elderly population proteinuria is an independent predictor of all-cause and cardiovascular mortality, while eGFR is not an independent predictor of all-cause mortality, and it is nominally significantly associated with cardiovascular mortality. However, mortality risk is higher in individuals with combined reduced eGFR and proteinuria.     

Long-term follow-up of participants in a health promotion program for treated hypertensives (ADAPT)

Background and aimsImprovements in a lifestyle modification program for hypertensives were maintained 1 year later. Longer follow-up in such studies is limited; we therefore re-assessed participants after an additional 2 years in which there was no contact with program facilitators.Methods and resultsParticipants randomised to usual care (N = 118) or a 4-month lifestyle program (N = 123) were previously assessed after 4 months and 1 year. After a further 2 years, diet, alcohol intake, physical activity, weight, waist girth, ambulatory blood pressure (BP), blood lipids, glucose and insulin were measured (usual care N = 64; program N = 76). Statistically significant net changes, relative to usual care, included blood cholesterol (−0.2 mmol/L, 95% CI 0.1–0.4); physical activity (53 min/week, 95% CI 15–91); dietary saturated fat (−1.9% energy, 95% CI −0.1 to −3.8); fish (3.2 serves/month, 95% CI 0.7–5.7); vegetables (9.1 serves/month, 95% CI 3.2–15.1); and sweet foods (−6.2 serves/month, 95% CI −1.1 to −11.3). Between-group changes in weight (−0.7 kg, 95% CI −1.8–0.4), BP (systolic 1.4 mmHg, 95% CI −0.7–3.5)/diastolic 1.0 mmHg, 95% CI −0.3–2.4) and Framingham risk (usual care: men 12.1%, women 3.7%; program: men 12.2%; women 3.5%) did not differ significantly.ConclusionContinued reinforcement with long-term follow-up is needed in lifestyle modification programs.     

Renal safety of intensive cholesterol-lowering treatment with rosuvastatin: a retrospective analysis of renal adverse events among 40,600 participants in the rosuvastatin clinical development program

ObjectiveIntensive lowering of low-density lipoprotein cholesterol (LDL-C) with statins reduces cardiovascular risk but can cause liver-, muscle-, and possibly renal-related adverse events (AEs). We assessed the effects of rosuvastatin on the risk of developing renal impairment or renal failure among participants in the rosuvastatin clinical development program.MethodsThe analysis was based on AE data reported by investigators from 36 studies that included 40,600 participants who did not have advanced, pre-existing renal disease. Rates of renal AEs were determined based on time to first occurrence of renal impairment or renal failure.ResultsRenal impairment or renal failure was reported in 536 study participants during 72,488 patient-years of follow-up. Renal event rates were higher in patients with history of heart failure (n = 5011), hypertension (n = 21,864), diabetes (n = 5165), or estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² (n = 9507) at baseline but did not differ with rosuvastatin compared with placebo or with rosuvastatin 40 mg compared with rosuvastatin 10 mg. Relative risk (RR) estimates obtained from pooled analysis of placebo-controlled trials were RR: 1.03 (95% CI: 0.86–1.23, p = 0.777) for any reported renal impairment or renal failure event, RR: 1.02 (95% CI: 0.76–1.37, p = 0.894) for serious renal AEs, and RR: 0.70 (95% CI: 0.36–1.35, p = 0.282) for renal AEs leading to death.ConclusionThese findings suggest that intensive LDL-C-lowering treatment with rosuvastatin does not affect the risk of developing renal insufficiency or renal failure in patients who do not have advanced, pre-existing renal disease.     

Taxa de filtração glomerular: que fórmula deverá ser usada em doentes com enfarte agudo do miocárdio?

IntroductionThere is disagreement regarding the best method for assessing renal dysfunction in patients with myocardial infarction (MI). This study aims to compare two commonly used formulas for measuring glomerular filtration rate (GFR) (Cockcroft-Gault [CG] and modification of diet in renal disease [MDRD]) in terms of predicting extent of coronary artery disease (CAD) and short- and long-term cardiovascular risk.MethodsWe studied 452 patients admitted to a cardiac intensive care unit (ICU) with MI (age 69.01 ± 13.64 years; 61.7% male, 38.5% diabetic) and followed for two years. CG and MDRD GFR estimates were compared in terms of prediction of CAD extent, in-hospital mortality risk and cardiovascular risk during follow-up.ResultsGFR <60 ml/min/1.73 m² using the MDRD formula was associated with a tendency for more extensive CAD (2.70 affected segments vs. 2.20, p = 0.052) and higher two-year mortality risk (p < 0.001, OR 3.84, 95% CI 2.04-7.22) and risk for reinfarction (p < 0.001, OR 4.09, 95% CI 2.00-8.39), decompensated heart failure (DHF) (p < 0.001, OR 3.95, 95% CI 2.04-7.66) and combined cardiovascular endpoints (p = 0.001, OR 2.47, 95% CI 1.47-4.17). Using the CG formula, GFR < 60 ml/min/1.73 m² only predicted higher risk for DHF (p = 0.016, OR 4.5, 95% CI 1.11-16.57), despite a tendency for more overall combined cardiovascular endpoints (p = 0.09, OR 2.84). Both formulas predicted in-hospital mortality.Discussion/ConclusionsThis study confirmed the value of GFR in predicting various cardiovascular endpoints in patients with MI. Compared to the CG formula, the MDRD formula was significantly more accurate in predicting the severity of CAD and two-year CV risk in patients admitted to the ICU with MI.     

Angiotensin-converting enzyme gene single polymorphism as a genetic biomarker of diabetic peripheral neuropathy: longitudinal prospective study

BackgroundIdentifying patients at risk of developing diabetic peripheral neuropathy (DPN) is of paramount importance in those with type 2 diabetes mellitus (T2DM) to provide and anticipate secondary prevention measures as well as intensify action on risk factors, particularly so in primary care. Noteworthy, the incidence of DPN remains unknown in our environment.Aims(i) To analyze a single angiotensin-converting enzyme (ACE) gene polymorphism (D/I) as a genetic marker of risk of developing DPN, and (ii) to determine the incidence of DPN in our environment.Research design and methodsLongitudinal study with annual follow-up for 3 years involving a group of T2DM (N = 283) randomly selected. ACE gene polymorphism distribution (I = insertion; D = deletion) was determined. DPN was diagnosed using clinical and neurophysiology evaluation.ResultsBaseline DPN prevalence was 28.97% (95% CI, 23.65–34.20). ACE polymorphism heterozygous genotype D/I presence was 60.77% (95% CI, 55.05–66.5) and was independently associated with a decreased risk of DPN (RR, 0.51; 95% CI, 0.30–0.86). DPN correlated with age (P < 0.001) but not with gender (P = 0.466) or time of evolution of T2DM (P = 0.555). Regarding end point, DPN prevalence was 36.4% (95% CI, 30.76–42.04), and accumulated incidence was 10.4% 3 years thereafter. In the final Poisson regression analysis, the presence of heterozygous genotype remained independently associated with a decreased risk of DPN (RR, 0.71; (95% CI, 0.53–0.96). DPN presence remained correlated with age (P = 0.002), but not with gender (P = 0.490) or time of evolution (P = 0.630).ConclusionsIn our series, heterozygous ACE polymorphism (D/I) stands as a protective factor for DPN development. Accumulated incidence of DPN was relevant. Further prospective studies are warranted.     

CYP2C19*2/ABCB1-C3435T polymorphism and risk of cardiovascular events in coronary artery disease patients on clopidogrel: Is clinical testing helpful?

BackgroundStudies evaluating CYP2C19*2 and ABCB1-C3435T polymorphisms have shown conflicting results. We performed this meta-analysis to evaluate role of clinical testing for these polymorphisms in CAD patients on clopidogrel.Methods19,601 patients from 14 trials were analyzed. The endpoints were major adverse cardiovascular events (MACE), cardiovascular (CV) death, stent thrombosis (ST), myocardial infarction (MI), stroke and major bleeding. Combined relative risks (RR) with 95% confidence intervals (CI) were computed for each outcome by using standard methods of meta-analysis and test parameters were computed.ResultsCYP2C19*2 polymorphism was associated with higher risk of MACE [RR: 1.28, CI: 1.06–1.54; p = 0.009], CV death [RR: 3.21, CI: 1.65–6.23; p = 0.001], MI [RR: 1.36, CI: 1.12–1.65; p = 0.002], ST [RR: 2.41, CI: 1.69–3.41; p < 0.001]. No difference was seen in major bleeding events [RR: 1.02, CI: 0.86–1.20; p = 0.83]. Subgroup analysis showed similar results for elective PCI [RR: 1.34, CI: 1.01–1.76; p = 0.03], and PCI with DES [RR: 1.53, CI: 1.029–1.269; p = 0.03]. CYP2C19*2 polymorphism has very low sensitivity (28–58%), specificity (71–73%), positive predictive value (3–10%) but good negative predictive value (92–99%). ABCB1-C3435T polymorphism analysis revealed similar MACE [RR: 1.13, CI: 0.99–1.29; p = 0.06], ST [RR: 0.88, CI: 0.52–1.47; p = 0.63] and major bleeding [RR: 1.04, CI: 0.87–1.25; p = 0.62] in both groups.ConclusionIn CAD patients on clopidogrel therapy, CYP2C19*2 polymorphism is associated with significantly increased adverse cardiovascular events. However, due to the low positive predictive value, routine genetic testing cannot be recommended at present.     

Follow-up association study of linkage regions reveals multiple candidate genes for carotid plaque in Dominicans

BackgroundIt has been well established that cilostazol has anti-proliferative effect against in-stent restenosis. However, it remains unclear whether cilostazol can prevent the progression of carotid atherosclerosis.Methods and resultsWe performed a meta-analysis of all relevant randomized controlled trials (RCTs) to evaluate the effect of cilostazol on the progression of carotid intima-media thickness (IMT). Five RCTs with 698 patients [597 subjects with type 2 diabetes mellitus (T2DM)] were included in this study. Cilostazol was associated with a significant reduction in the progression of carotid IMT (WMD, ?0.08 mm, 95% CI ?0.13, ?0.04; P = 0.00003). Subgroup analysis shows that cilostazol monotherapy or addition to dual antiplatelet therapy (aspirin and clopidogrel) was superior to placebo (WMD, ?0.04 mm, 95% CI ?0.05, ?0.03; P < 0.00001), no antiplatelet medication (WMD, ?0.12 mm, 95% CI ?0.21, ?0.03; P = 0.008), aspirin monotherapy (WMD, ?0.06 mm, 95% CI ?0.12, 0.00; P = 0.04) or dual antiplatelet therapy (WMD, ?0.16 mm, 95% CI ?0.30, ?0.02; P = 0.03) in preventing the progression of carotid IMT. Cilostazol resulted in a significant decrease in total cholesterol (WMD ?8.47 mg/dl, 95% CI ?14.18, ?2.75; P = 0.004) and LDL-C (WMD ?8.25 mg/dl, 95% CI ?14.15, ?2.36; P = 0.006) and favorable trends in reducing triglyceride (WMD ?15.83 mg/dl, 95% CI ?32.14, 0.48; P = 0.06).ConclusionIt suggests that cilostazol may have beneficial effects in preventing the progression of carotid atherosclerosis and improving pro-atherogenic lipid profile, especially in patients with T2DM. Whether the anti-atherosclerotic effect of cilostazol is independent of improving pro-atherogenic dyslipidemia is worth further investigation.     

Carotid intima-media thickness, hs-CRP and TNF-α are independently associated with cardiovascular event risk in patients with atherosclerotic occlusive disease

This prospective study aimed to determine whether carotid intima-media thickness (CIMT) and biomarkers can enhance the predictive value of classic atherosclerosis risk factors (RFs) for cardiovascular (CV) event risk in patients with confirmed atherosclerosis.MethodsBaseline levels of hs-CRP, Tumor Necrosis Factor alpha (TNF-α), Transforming Growth Factor beta (TGF-β), Interleukin-6 (IL-6), Interleukin-10 (IL-10) and Nt-proBNP were measured in 304 subjects (189 men) aged 64.2 ± 9.4 years, with confirmed atherosclerotic occlusive disease. Maximum CIMT values of common, bulb and internal carotid arteries were measured and expressed as mean CIMT value. The incidences of CV death, myocardial infarction (MI), ischemic stroke (IS) and symptomatic lesion progression were recorded.ResultsDuring 44.7 ± 12.1 months of follow-up, CV events occurred in 61 (20.1%) patients. Age (odds ratio: OR = 1.04; p = 0.013), diabetes (OR = 2.01; p = 0.007), LDL-cholesterol > 3.35 mmol/L (OR = 2.03; p = 0.007), previous MI (OR = 2.14; p = 0.003) and previous IS (OR = 3.35; p < 0.001) were found independent CV event RFs. Adding biomarkers or CIMT to classic RFs revealed that levels of TNF-α > 6 pg/mL (OR = 1.77; p = 0.024), hs-CRP > 6 mg/L (OR = 1.69; p = 0.009) or CIMT > 1.25 mm (OR = 5.11; p < 0.001) were independently associated with CV event risk. While Nt-proBNP was found RF of CV death (OR = 1.19; p = 0.003) and MI (OR = 1.19; p = 0.002). In patients with RFs plus TNF-α > 6 pg/mL and hs-CRP > 6 mg/L, a 2- and 5-year event-free survival was 8% and 4%, respectively, as compared to 42% and 33% in those with RFs but lower TNF-α and hs-CRP levels. While, CIMT < 1.25 mm increased a 2- and 5-year CV event-free survival probability to 79% and 73%, respectively, despite classic RFs presence.ConclusionAdditive value of TNF-α, hs-CRP and CIMT to classic RFs in CV risk stratification was found in patients with confirmed atherosclerosis. Nt-proBNP was found an independent risk factor of CV death and MI.