Manan Pareek

Follow-up duration influences the relative importance of OGTT and optimal timing of glucose measurements for predicting future type 2 diabetes

OBJECTIVE To examine the impact of follow-up duration on the incremental prognostic yield of a baseline oral glucose tolerance test (OGTT) for predicting type 2 diabetes and to assess the discrimination ability of blood glucose (BG) obtained at different time points during OGTT. DESIGN A prospective, population-based cohort study (Malmö Preventive Project) with inclusion of subjects from 1974 to 1992. METHODS A total of 5256 men without diabetes, who had BG measured at 0, 20, 40, 60, 90, and 120 min during OGTT (30 g/m2 glucose), were followed for 30 years. Incident type 2 diabetes was recorded using registries. The performance of OGTT added to a clinical prediction model (age, body mass index (BMI), diastolic blood pressure, fasting BG, triglycerides, and family history of diabetes) was assessed using Harrells concordance index (C-index) and integrated discrimination improvement (IDI). RESULTS Median age was 48 years, mean BMI 24.9 kg/m2, and mean fasting BG 4.7 mmol/L. Models with added post-load BG performed better than the clinical model (C-index: P = 0.08 for BG at 120 min at 5 years, otherwise P ≤ 0.045; IDI: P ≥ 0.06 for BG at 60 and 90 min at 5 years, otherwise P ≤ 0.01). With a longer follow-up duration, C-index decreased, and the C-index increase associated with OGTT was attenuated. Models including BG at 60 or 90 min performed significantly better than the model with BG at 120 min, evident beyond follow-up of 10 and 5 years, respectively. CONCLUSIONS OGTT provided incremental prognostic yield for type 2 diabetes prediction. BG measured at 60 or 90 min provided better discrimination than BG at 120 min.

Worsening diastolic function is associated with elevated fasting plasma glucose and increased left ventricular mass in a supra-additive fashion in an elderly, healthy, Swedish population

AIMS To examine whether increasing fasting plasma glucose (FPG) levels were associated with worsening left ventricular (LV) diastolic function, independently of LV mass index (LVMI) in elderly, otherwise healthy subjects. METHODS AND RESULTS We tested cross-sectional associations between echocardiographically determined averaged E/é ratio/diastolic function, LVMI, cardiovascular risk factors, and FPG categorized as normal (NFG), impaired (IFG), and new-onset diabetes mellitus (DM), in 483 men and 208 women aged 56-79 years without overt cardiovascular disease, who received no cardiovascular, anti-diabetic, or lipid-lowering drugs and had a preserved LV ejection fraction >50%. Median E/é was significantly higher among subjects with diabetes than those without (8 vs. 7; p = 0.03), as was the prevalence of grade 2 or 3 diastolic dysfunction (25% vs. 16%; p = 0.02). E/é and diastolic function were significantly associated with LVMI (p ≤ 0.002), but not FPG category, on multivariable analysis. However, interaction analyses revealed that increasing LVMI was primarily associated with worsening diastolic function (higher E/é) in subjects with FPG > 6 mmol/L (β=0.005 for IFG and DM vs. 0.001 for NFG; p = 0.02), whereas increasing systolic blood pressure was primarily associated with worsening diastolic function (higher E/é) in subjects with FPG ≤ 6.9 mmol/L (β = 0.005 for NFG and 0.003 for IFG vs. -0.001 for DM; p=0.001). CONCLUSION Diastolic dysfunction was significantly more prevalent among patients with DM than those without. The importance of LVMI increased, but the importance of systolic blood pressure decreased with higher FPG category.

Single and multiple cardiovascular biomarkers in subjects without a previous cardiovascular event

Aims To assess the incremental value of biomarkers, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), growth differentiation factor 15 (GDF-15), and procollagen type 1 N-terminal propeptide (P1NP), in predicting incident cardiovascular events and mortality among asymptomatic individuals from the general population, beyond traditional risk factors, including fasting glucose and renal function (cystatin C), medication use, and echocardiographic measures. Methods and results Prospective population-based cohort study of 1324 subjects without a previous cardiovascular event, who underwent baseline echocardiography and biomarker assessment between 2002 and 2006. The clinical endpoint was the composite of myocardial infarction, invasively treated stable/unstable ischemic heart disease, heart failure, stroke, or all-cause mortality. Predictive capabilities were evaluated using Cox proportional-hazards regression, Harrell’s concordance index (C-index), and net reclassification improvement. Median age was 66 (interquartile range: 60–70) years, and 413 (31%) were female. During median 8.6 (interquartile range: 8.1–9.2) follow-up years, 368 (28%) composite events occurred. NT-proBNP, hs-TnT, GDF-15, and IL-6 were significantly associated with outcome, independently of traditional risk factors, medications, and echocardiography (p < 0.05 for all). Separate addition of NT-proBNP and GDF-15 to traditional risk factors, medications, and echocardiographic measurements provided significant improvements in discriminative ability (NT-proBNP: C-index 0.714 vs. 0.703, p = 0.03; GDF-15: C-index 0.721 vs. 0.703, p = 0.02). Both biomarkers remained significant predictors of outcome upon inclusion in the same model (p < 0.05 for both). Conclusions NT-proBNP and GDF-15 each enhance prognostication beyond traditional risk factors, glucose levels, renal function, and echocardiography in individuals without known cardiovascular disease.

Lessons learned from the 1-hour post-load glucose level during OGTT: Current screening recommendations for dysglycaemia should be revised

This perspective covers a novel area of research describing the inadequacies of current approaches for diagnosing dysglycaemia and proposes that the 1‐hour post‐load glucose level during the 75‐g oral glucose tolerance test may serve as a novel biomarker to detect dysglycaemia earlier than currently recommended screening criteria for glucose disorders. Considerable evidence suggests that a 1‐hour post‐load plasma glucose value ≥155 mg/dl (8.6 mmol/L) may identify individuals with reduced β‐cell function prior to progressing to prediabetes and diabetes and is highly predictive of those likely to progress to diabetes more than the HbA1c or 2‐hour post‐load glucose values. An elevated 1‐hour post‐load glucose level was a better predictor of type 2 diabetes than isolated 2‐hour post‐load levels in Indian, Japanese, and Israeli and Nordic populations. Furthermore, epidemiological studies have shown that a 1‐hour PG ≥155 mg/dl (8.6 mmol/L) predicted progression to diabetes as well as increased risk for microvascular disease and mortality when the 2‐hour level was <140 mg/dl (7.8 mmol/L). The risk of myocardial infarction or fatal ischemic heart disease was also greater among subjects with elevated 1‐hour glucose levels as were risks of retinopathy and peripheral vascular complications in a Swedish cohort. The authors believe that the considerable evidence base supports redefining current screening and diagnostic recommendations with the 1‐hour post‐load level. Measurement of the 1‐hour PG level would increase the likelihood of identifying a larger, high‐risk group with the additional practical advantage of potentially replacing the conventional 2‐hour oral glucose tolerance test making it more acceptable in a clinical setting.

Factors associated with diagnostic discrepancy for left ventricular hypertrophy between electrocardiography and echocardiography

Abstract Objective: To investigate the influence of cardiovascular risk factors, including fasting plasma glucose (FPG), on the association between electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH) in an elderly population. Methods: We tested cross-sectional associations between electrocardiographic and echocardiographic LVH, defining LVH according to the Sokolow-Lyon voltage combination, Cornell voltage-duration product, or left ventricular mass index (LVMI). Differences between standardized LVMI and Sokolow-Lyon voltage combination or Cornell voltage-duration product (absolute value/cut-off value for LVH) were used as outcome variables in order to identify explanatory variables associated with diagnostic discrepancies between ECG and echocardiography. Results: Of the 1382 subjects included, 77% did not display any signs of LVH, 6% had LVH defined by ECG only, 13% had LVH defined by echocardiography only, and 5% had LVH on both ECG and echocardiography. Older subjects and those with higher blood pressure and RWT were more likely to have a relatively greater LVMI on echocardiography than that predicted on ECG (odds ratio: 1.65 per 10 years (95% confidence interval (CI): 1.27-2.15), p = .0002, odds ratio: 1.17 per 10 mmHg (95% CI: 1.09-1.25), p < .0001, and odds ratio: 1.21 per 0.10 (95% CI: 1.02-1.42), p = .03). In addition, discrepancy was also seen in females and subjects receiving antihypertensive medication (odds ratio: 1.41 (95% CI: 1.04-1.89), p = .03 and odds ratio: 1.41 (95% CI: 1.06-1.87), p = .02), but FPG did not independently influence discrepancy between ECG and echocardiography. Conclusion: Age, blood pressure, female sex, greater RWT and use of antihypertensive medication were associated with a greater risk of non-consistency between LVH determined by ECG and echocardiography.

4B.07: BASELINE CARDIAC TROPONIN T LEVELS ARE ELEVATED IN SUBJECTS WITH UNTREATED DIABETES MELLITUS: A CROSS-SECTIONAL STUDY.

Objective: Cardiac troponins are biomarkers of myocardial injury and serve both diagnostic and prognostic purposes. Even mild elevations represent subclinical myocardial damage in the general population. The objective of this study was to investigate the relationship between glucometabolic status and cardiac troponin T in middle-aged or older apparently healthy subjects. Design and method: We examined cross-sectional associations between high-sensitivity cardiac troponin T (hsTnT) and FPG categorized as normal fasting glucose (NFG: FPG</=6.0mmol/L), impaired fasting glucose (IFG: FPG 6.1–6.9mmol/L), and diabetes mellitus (DM: FPG>/=7.0mmol/L), in 535 men and 226 women aged 56–79 years without overt cardiovascular disease who received no cardiovascular, antidiabetic or lipid lowering drugs, using multiple linear regression analysis. Results: FPG category (r = 0.159; p < 0.001) was positively correlated with hsTnT. Mean hsTnT levels increased significantly with worsening glucometabolic status (NFG: 7.55 ng/L +/- standard deviation 3.99 ng/L; IFG: 8.09 ng/L +/- 6.81 ng/L; DM: 10.28 ng/L +/- 7.55 ng/L; p < 0.001). Levels were significantly higher in subjects with DM compared to NFG (p < 0.001) and IFG (p = 0.005), but there was no significant difference between subjects with NFG and IFG (p = 0.26). After adjusting for age and sex, FPG category remained significantly predictive of hsTnT (B = 1.08 [95% confidence interval (CI), 0.56–1.59]; p < 0.001). After further adjusting for traditional cardiovascular risk factors, cystatin C levels, and electrocardiographic left ventricular hypertrophy (LVH) defined by the Sokolow-Lyon index and/or Cornell voltage-duration product, FPG category remained significantly associated with hsTnT (B = 0.87 [95% CI, 0.35–1.39]; p = 0.001), independently of age (B = 0.29 [95% CI, 0.22–0.36]; p < 0.001), sex (B = 2.08 [95% CI, 1.20–2.95]; p < 0.001), systolic blood pressure (B = 0.032 [95% CI, 0.012–0.051]; p = 0.001), and cystatin C (B = 3.69 [95% CI, 1.60–5.79]; p = 0.001). There was a significant interaction between FPG category and age (NFG: B = 0.22 [95% CI, 0.16–0.29]; IFG: B = 0.33 [95% CI, 0.18–0.48]; DM: B = 0.41 [95% CI, 0.20–0.62]; p = 0.03). Conclusions: In middle-aged or older apparently healthy subjects, untreated DM was associated with higher levels of hsTnT, independently of traditional cardiovascular risk factors. The importance of age increased with worsening glucometabolic status.

One-hour glucose value as a long-term predictor of cardiovascular morbidity and mortality: the Malmö Preventive Project

OBJECTIVE To examine the predictive capability of a 1-h vs 2-h postload glucose value for cardiovascular morbidity and mortality. DESIGN Prospective, population-based cohort study (Malmö Preventive Project) with subject inclusion 1974-1992. METHODS 4934 men without known diabetes and cardiovascular disease, who had blood glucose (BG) measured at 0, 20, 40, 60, 90 and 120 min during an OGTT (30 g glucose per m2 body surface area), were followed for 27 years. Data on cardiovascular events and death were obtained through national and local registries. Predictive capabilities of fasting BG (FBG) and glucose values obtained during OGTT alone and added to a clinical prediction model comprising traditional cardiovascular risk factors were assessed using Harrells concordance index (C-index) and integrated discrimination improvement (IDI). RESULTS Median age was 48 (25th-75th percentile: 48-49) years and mean FBG 4.6 ± 0.6 mmol/L. FBG and 2-h postload BG did not independently predict cardiovascular events or death. Conversely, 1-h postload BG predicted cardiovascular morbidity and mortality and remained an independent predictor of cardiovascular death (HR: 1.09, 95% CI: 1.01-1.17, P = 0.02) and all-cause mortality (HR: 1.10, 95% CI: 1.05-1.16, P < 0.0001) after adjusting for various traditional risk factors. Clinical risk factors with added 1-h postload BG performed better than clinical risk factors alone, in predicting cardiovascular death (likelihood-ratio test, P = 0.02) and all-cause mortality (likelihood-ratio test, P = 0.0001; significant IDI, P = 0.0003). CONCLUSION Among men without known diabetes, addition of 1-h BG, but not FBG or 2-h BG, to clinical risk factors provided incremental prognostic yield for prediction of cardiovascular death and all-cause mortality.

A fatal case of primary cardiac chondrosarcoma presenting with amaurosis fugax

A 64-year-old previously healthy woman consulted her general practitioner because of recurrent episodes of right-sided monocular transient visual loss (ie, amaurosis fugax). At first, these symptoms were followed over time, but as the attacks worsened, and were accompanied by dizziness and general discomfort, the patient was admitted to the department of neurology for further investigations. CT of the brain was normal; however, during admission, the patient developed rapid atrial fibrillation and was transferred to the department of cardiology. Transthoracic echocardiography revealed a massive tumour on the atrial side of the anterior mitral valve leaflet, partly obstructing the mitral valve inflow. The tumour was excised and a biological prosthetic mitral valve inserted. The tumour was histologically determined to be a highly malignant dedifferentiated chondrosarcoma. After 6 months, the tumour relapsed and expanded aggressively to completely obstruct the mitral valve inflow, ultimately leading to cardiac arrest and death.

Highlights from the 65th American College of Cardiology Annual Scientific Session (ACC 2016)

This years American College of Cardiology Scientific Session (ACC 2016) featured a good number of studies on drug therapies in both primary and secondary preventive settings. In this update, we will present some of the studies that may be of particular significance to the practising physician. In the preventive section, the HOPE-3 (Heart Outcomes Prevention Evaluation 3) trial stole the limelight, first and foremost by strengthening faith in statins—this time by extending their potential benefit to racially and ethnically diverse subjects without cardiovascular disease who did not necessarily have elevated levels of LDL-cholesterol, C-reactive protein, hypertension, or diabetes.1 In the cholesterol-lowering arm of the study, 5874 women aged ≥60 years and 6831 men aged ≥55 years with an intermediate risk profile were randomly assigned to receive either rosuvastatin 10 mg once daily or placebo. The mean baseline LDL-cholesterol level was ∼128 mg/dL, and was ∼30 mg/dL lower in the rosuvastatin arm than in the placebo arm at the end of the trial. After a median follow-up of 5.6 years, the first co-primary endpoint (the composite of myocardial infarction, stroke, and cardiovascular death) occurred significantly less frequently in the rosuvastatin group than in the placebo group [3.7% vs. 4.8%, hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.64–0.91; P = 0.002]. The findings were consistent among pre-specified subgroups. Statin therapy was well tolerated, with an absolute excess of only 1.1% (5.8% vs. 4.7%, P = 0.005) for muscle pain or weakness. Conversely, HOPE-3 left us less optimistic regarding blood pressure lowering in such individuals.2 The two-by-two factorial design allowed for randomization of the study population to low-dose antihypertensive therapy with candesartan 16 mg per day plus hydrochlorothiazide 12.5 mg per day vs. placebo. At 5.6 years, active treatment resulted in an average blood pressure lowering of 6.0/3.0 mmHg above … [↵][1]*Corresponding author. Brigham and Womens Hospital Heart & Vascular Center, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. Tel: +1 857 307 1992, Email: dlbhattmd{at}post.harvard.edu [1]: #xref-corresp-1-1