Naveed Sattar

University of Glasgow, Glasgow, Scotland, United Kingdom

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Publications (538)5128.17 Total impact

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    Shurooq A Boodai · Lynne M Cherry · Naveed A Sattar · John J Reilly ·
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    ABSTRACT: Background Childhood and adolescent obesity is associated with insulin resistance, abnormal glucose metabolism, hypertension, dyslipidemia, inflammation, liver disease, and compromised vascular function. The purpose of this pilot study was to determine the prevalence of cardiometabolic risk factor abnormalities and metabolic syndrome (MetS) in a sample of obese Kuwaiti adolescents, as prevalence data might be helpful in improving engagement with obesity treatment in future. Methods Eighty obese Kuwaiti adolescents (40 males) with a mean (standard deviation) age of 12.3 years (1.1 years) participated in the present study. All participants had a detailed clinical examination and anthropometry, blood pressure taken, and assessment of fasting levels of C-reactive protein, intracellular adhesion molecule, interleukin-6, fasting blood glucose, insulin, liver function tests (alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase), lipid profile (cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides), insulin resistance by homeostasis model assessment, and adiponectin. MetS was assessed using two recognized criteria modified for use in younger individuals. Results The cardiometabolic risk factors with highest prevalence of abnormal values included aspartate aminotransferase (88.7% of the sample) and insulin resistance by homeostasis model assessment (67.5%), intracellular adhesion molecule (66.5%), fasting insulin (43.5%), C-reactive protein (42.5%), low-density lipoprotein cholesterol (35.0%), total cholesterol (33.5%), and systolic blood pressure (30.0%). Of all participants, 96.3% (77/80) had at least one impaired cardiometabolic risk factor as well as obesity. Prevalence of MetS was 21.3% according to the International Diabetes Federation definition and 30% using the Third Adult Treatment Panel definition. Conclusion The present study suggests that obese Kuwaiti adolescents have multiple cardiometabolic risk factor abnormalities. Future studies are needed to test the benefits of intervention in this high-risk group. They also suggest that prevention of obesity in children and adults should be a major public health goal in Kuwait.
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 10/2014; 7:505-11. DOI:10.2147/DMSO.S66156
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    Daniel I Swerdlow · Naveed Sattar ·
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    ABSTRACT: In this issue of the journal, Erqou and colleagues (DOI 10.1007/s00125-014-3374-x ) report, in a systematic review and meta-analysis of randomised trials, a very modest (1.3 mmol/mol or 0.12%) albeit significant increase in HbA1c in patients with diabetes treated with statins, compared with control. Here, we discuss the clinical relevance of the findings. Given the overwhelming benefit of statins on cardiovascular outcomes in diabetes, current guidelines recommending statins for primary prevention in type 2 diabetes should not change, and any effect on microvascular risk is likely to be minimal. Of course, all patients recommended for statin treatment, whether they have diabetes or not, should now be warned of a slight potential for dysglycaemia on starting statins, but at the same time they should be told that very modest lifestyle improvement will help offset this dysglycaemia risk. Finally, we remind colleagues that nearly all drugs have side effects and we should not be surprised by this statin-dysglycaemia effect, which can be easily managed.
    Diabetologia 10/2014; 57(12). DOI:10.1007/s00125-014-3409-3 · 6.67 Impact Factor
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    ABSTRACT: Background: Visit-to-visit variability in blood pressure is an independent predictor of cardiovascular disease. This study investigates biological correlates of intra-individual variability in blood pressure in older persons. Methods: Nested observational study within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) among 3,794 male and female participants (range 70-82 years) with a history of, or risk factors for cardiovascular disease. Individual visit-to-visit variability in systolic and diastolic blood pressure and pulse pressure (expressed as 1 SD in mm Hg) was assessed using nine measurements over 2 years. Correlates of higher visit-to-visit variability were examined at baseline, including markers of inflammation, endothelial function, renal function and glucose homeostasis. Results: Over the first 2 years, the mean intra-individual variability (1 SD) was 14.4mm Hg for systolic blood pressure, 7.7mm Hg for diastolic blood pressure, and 12.6mm Hg for pulse pressure. After multivariate adjustment a higher level of interleukin-6 at baseline was consistently associated with higher intra-individual variability of blood pressure, including systolic, diastolic, and pulse pressure. Markers of endothelial function (Von Willebrand factor, tissue plasminogen activator), renal function (glomerular filtration rate) and glucose homeostasis (blood glucose, homeostatic model assessment index) were not or to a minor extent associated with blood pressure variability. Conclusion: In an elderly population at risk of cardiovascular disease, inflammation (as evidenced by higher levels of interleukin-6) is associated with higher intra-individual variability in systolic, diastolic, and pulse pressure.
    American Journal of Hypertension 10/2014; 28(4). DOI:10.1093/ajh/hpu181 · 2.85 Impact Factor
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    ABSTRACT: Aims/hypothesis: To determine the extent to which gestational fasting and postload levels of glucose explain differences in infant fat mass between UK-born Pakistani and white British infants. Methods: Analyses were undertaken in a prospective pregnancy cohort study of 1,415 women and their singleton live-born infants (629 white British and 786 Pakistani). Infant fat mass was assessed by cord-blood leptin levels and fetal insulin secretion by cord-blood insulin levels. Maternal OGTTs were completed at 26-28 weeks of gestation. Results: Pakistani women had higher fasting and postload glucose levels and greater incidence of gestational diabetes than white British women. Higher fasting and postload glucose levels were associated with higher cord-blood levels of insulin and leptin in all participants, irrespective of ethnicity. Cord-blood leptin levels were 16% (95% CI 6, 26) higher in Pakistani than in white British infants. After adjustment for fasting glucose levels, this difference attenuated to 7% (-3, 16), and with additional adjustment for cord-blood insulin levels it attenuated further to 5% (-4, 14). Path analyses supported the hypothesis that fasting glucose levels mediate the relationship of Pakistani ethnicity to greater fat mass at birth, as measured by cord-blood leptin levels; on average, 19% of this mediation involved fetal insulin secretion. Postload glucose levels did not act as an important mediator of ethnic differences in cord-blood leptin levels. Results were very similar when 130 women with gestational diabetes were removed. Conclusions/interpretation: These novel findings suggest a role of maternal pregnancy glycaemia in mediating differences in fat mass between Pakistani and white British infants.
    Diabetologia 10/2014; 57(12). DOI:10.1007/s00125-014-3386-6 · 6.67 Impact Factor
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    ABSTRACT: Objective To evaluate associations between lipid levels, inflammation, and rheumatoid arthritis (RA) disease activity, at baseline and during treatment, with the risk of major adverse cardiovascular events (MACE) in tocilizumab-treated patients with RA.Methods In retrospective post hoc analyses, data were pooled for 3,986 adult patients with moderate to severe RA who received ≥1 dose of tocilizumab (4 mg/kg or 8 mg/kg) intravenously every 4 weeks in randomized controlled trials and extension studies. Cox proportional hazards modeling was used to evaluate associations between baseline characteristics and posttreatment changes in laboratory and disease characteristics (week 24) and change in disease activity and laboratory values from baseline to week 24 with the risk of future MACE during extended followup.ResultsWe identified 50 independently adjudicated cases of MACE during 14,683 patient-years of followup (0.34 MACE cases/100 patient-years). At baseline, age, a history of cardiac disorders, the Disease Activity Score in 28 joints (DAS28), and the total cholesterol:high-density lipoprotein cholesterol ratio were independently associated with MACE in multivariable models (P < 0.05 for all). During treatment, a higher DAS28 and higher swollen and tender joint counts at week 24 were associated with future MACE. In separate models, greater reductions in the DAS28 and joint counts from baseline to week 24 were inversely associated with future MACE; changes in lipid parameters were not statistically significantly associated with the risk of MACE.Conclusion In this population of patients treated with tocilizumab, an association was observed between the baseline total cholesterol:high-density lipoprotein cholesterol ratio and an increased risk of MACE. The risk of MACE while receiving treatment, however, was associated with control of disease activity but not lipid changes. Larger studies are needed to confirm these findings.
    Arthritis and Rheumatology 10/2014; 67(2). DOI:10.1002/art.38920
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    ABSTRACT: Aims/hypothesis: Insulin resistance is commonly proposed as a precursor to both type 2 diabetes and cardiovascular disease (CVD), yet few studies have directly compared insulin resistance with both outcomes simultaneously and determined whether associations with each outcome differ in strength or are comparable. We assessed the association of fasting insulin and HOMA-IR with incident CVD and diabetes in older people. Methods: In the long-term follow-up of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) cohort, HOMA-IR measurement was available in 4,742 older people (70-82 years) without diabetes at baseline. Of these, 283 developed diabetes during the 3.2 year within-trial follow-up, while 1,943 all-cause deaths, 470 CHD deaths (identified from death records) and 590 fatal/non-fatal CVD events (identified from medical record linkage in the Scottish participants) occurred during an extended 8.6 years of total follow-up. Cause-specific Cox proportional-hazards models were fitted using multivariable models. Results: Higher HOMA-IR was associated with incident diabetes: HR 4.80 (95% CI 3.14, 7.33) comparing extreme thirds after adjustment for confounders. However, HOMA-IR in the top third was not associated with all-cause mortality, CHD mortality or fatal/non-fatal CVD: HR 1.02 (95% CI 0.90, 1.17), 1.03 (0.79, 1.36) and 0.94 (0.74, 1.20), respectively. Results were similar when fasting insulin was considered as an exposure. Conclusions/interpretation: Our data support insulin resistance as a predictor of diabetes in later life but, perhaps surprisingly, suggest this pathway is of negligible importance to CVD outcomes in the elderly.
    Diabetologia 09/2014; 57(12). DOI:10.1007/s00125-014-3383-9 · 6.67 Impact Factor
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    ABSTRACT: Background Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. Methods We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. Findings Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05–0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18–0·43), waist circumference (0·32 cm, 0·16–0·47), plasma insulin concentration (1·62%, 0·53–2·72), and plasma glucose concentration (0·23%, 0·02–0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00–1·05); the rs12916-T allele association was consistent (1·06, 1·03–1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18–1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10–0·38 in all trials; 0·33 kg, 95% CI 0·24–0·42 in placebo or standard care controlled trials and −0·15 kg, 95% CI −0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9–6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06–1·18 in all trials; 1·11, 95% CI 1·03–1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04–1·22 in intensive-dose vs moderate dose trials). Interpretation The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. Funding The funding sources are cited at the end of the paper.
    09/2014; DOI:10.1016/S0140-6736(14)61183-1
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    Naveed Sattar · Ewan Forrest · David Preiss ·

    BMJ Clinical Research 09/2014; 349(sep19 15):g4596. DOI:10.1136/bmj.g4596 · 14.09 Impact Factor
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    ABSTRACT: Aims/hypothesis The aim of this study was to investigate the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with traditional cardiovascular risk factors and incident cardiovascular events in older people with type 2 diabetes. Methods In the prospective phase of the Edinburgh Type 2 Diabetes Study, 1066 men and women aged 60 to 75 years with type 2 diabetes mellitus were followed for 4 years; 112 participants had an incident cardiovascular event. At baseline, cardiovascular risk factors, pre-existing cardiovascular disease and levels of NT-proBNP were evaluated. Results Raised plasma NT-proBNP levels were associated with these classical cardiovascular risk factors: increased duration of diabetes, use of insulin, raised BMI, reduced HDL-cholesterol, reduced renal function and use of lipid-lowering and anti-hypertensive medication (all p
    Diabetologia 09/2014; 57(12). DOI:10.1007/s00125-014-3375-9 · 6.67 Impact Factor
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    ABSTRACT: Background: Regular breakfast consumption may protect against type 2 diabetes risk in adults but little is known about its influence on type 2 diabetes risk markers in children. We investigated the associations between breakfast consumption (frequency and content) and risk markers for type 2 diabetes (particularly insulin resistance and glycaemia) and cardiovascular disease in children. Methods and findings: We conducted a cross-sectional study of 4,116 UK primary school children aged 9-10 years. Participants provided information on breakfast frequency, had measurements of body composition, and gave fasting blood samples for measurements of blood lipids, insulin, glucose, and glycated haemoglobin (HbA1c). A subgroup of 2,004 children also completed a 24-hour dietary recall. Among 4,116 children studied, 3,056 (74%) ate breakfast daily, 450 (11%) most days, 372 (9%) some days, and 238 (6%) not usually. Graded associations between breakfast frequency and risk markers were observed; children who reported not usually having breakfast had higher fasting insulin (percent difference 26.4%, 95% CI 16.6%-37.0%), insulin resistance (percent difference 26.7%, 95% CI 17.0%-37.2%), HbA1c (percent difference 1.2%, 95% CI 0.4%-2.0%), glucose (percent difference 1.0%, 95% CI 0.0%-2.0%), and urate (percent difference 6%, 95% CI 3%-10%) than those who reported having breakfast daily; these differences were little affected by adjustment for adiposity, socioeconomic status, and physical activity levels. When the higher levels of triglyceride, systolic blood pressure, and C-reactive protein for those who usually did not eat breakfast relative to those who ate breakfast daily were adjusted for adiposity, the differences were no longer significant. Children eating a high fibre cereal breakfast had lower insulin resistance than those eating other breakfast types (p for heterogeneity <0.01). Differences in nutrient intakes between breakfast frequency groups did not account for the differences in type 2 diabetes markers. Conclusions: Children who ate breakfast daily, particularly a high fibre cereal breakfast, had a more favourable type 2 diabetes risk profile. Trials are needed to quantify the protective effect of breakfast on emerging type 2 diabetes risk. Please see later in the article for the Editors' Summary.
    PLoS Medicine 09/2014; 11(9):e1001703. DOI:10.1371/journal.pmed.1001703 · 14.43 Impact Factor
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    ABSTRACT: Background: Increasing prevalence of diabetes worldwide is projected to lead to an increase in patients with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Aim: To provide contemporary estimates of the prevalence of ESRD and requirement for RRT among people with diabetes in a nationwide study and to report associated survival. Methods: Data were extracted and linked from three national databases: Scottish Renal Registry, Scottish Care Initiative-Diabetes Collaboration and National Records of Scotland death data. Survival analyses were modelled with Cox regression. Results: Point prevalence of chronic kidney disease (CKD)5 in 2008 was 1.63% of 19 414 people with type 1 diabetes (T1DM) compared with 0.58% of 167 871 people with type 2 diabetes (T2DM) (odds ratio for DM type 0.97, P = 0.77, on adjustment for duration. Although 83% of those with T1DM and CKD5 and 61% of those with T2DM and CKD5 were receiving RRT, there was no difference when adjusted for age, sex and DM duration (odds ratio for DM type 0.83, P = 0.432). Diabetic nephropathy was the primary renal diagnosis in 91% of people with T1DM and 58% of people with T2DM on RRT. Median survival time from initiation of RRT was 3.84 years (95% CI 2.77, 4.62) in T1DM and 2.16 years (95% CI: 1.92, 2.38) in T2DM. Conclusion: Considerable numbers of patients with diabetes continue to progress to CKD5 and RRT. Almost half of all RRT cases in T2DM are considered to be due to conditions other than diabetic nephropathy. Median survival time for people with diabetes from initiation of RRT remains poor. These prevalence data are important for future resource planning.
    QJM: monthly journal of the Association of Physicians 08/2014; 108(2). DOI:10.1093/qjmed/hcu170 · 2.50 Impact Factor
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    ABSTRACT: Background: Hyperparathyroidism and low vitamin D status have been implicated in the pathogenesis of heart failure (HF). We examined the prospective associations between parathyroid hormone (PTH), circulating 25-hydroxyvitamin D, and markers of mineral metabolism and risk of incident HF in older men with and without established cardiovascular disease. Methods and results: Prospective study of 3731 men aged 60 to 79 years with no prevalent HF followed up for a mean period of 13 years, in whom there were 287 incident HF cases. Elevated PTH (≥55.6 pg/mL; top quarter) was associated with significantly higher risk of incident HF after adjustment for lifestyle characteristics, diabetes mellitus, blood lipids, blood pressure, lung function, heart rate, renal dysfunction, atrial fibrillation, forced expiratory volume in 1 second, and C-reactive protein (hazards ratio, 1.66; 95% confidence interval, 1.30-2.13). The increased risk was seen in both men with and without previous myocardial infarction or stroke (hazards ratio, 1.72; 95% confidence interval, 1.07-2.76; hazards ratio, 1.70; 95% confidence interval, 1.25-2.30, respectively). Elevated PTH was significantly associated with N-terminal probrain natriuretic peptide, a marker of left ventricular wall stress. By contrast, 25-hydroxyvitamin D and other markers of mineral metabolism including serum calcium and phosphate showed no significant association with incident HF after adjustment for age. Conclusions: Elevated PTH, but not 25-hydroxyvitamin D or other markers of mineral metabolism, is associated with increased risk of HF in both older men with and without myocardial infarction/stroke. This increased risk was not explained by its association with known risk factors for HF. Further studies are now needed to elucidate the mechanisms underlying this association.
    Circulation Heart Failure 08/2014; 7(5). DOI:10.1161/CIRCHEARTFAILURE.114.001272 · 5.89 Impact Factor
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    ABSTRACT: Objective: Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cognitive impairment, which might be explained by cardiovascular diseases or risk factors. The aim of this study was to investigate the association of NT-proBNP with cognitive function and decline in older adults at high risk of cardiovascular disease. Methods: We studied 5,205 men and women (mean age = 75 years) who were recruited into the PROspective Study of Pravastatin in the Elderly at Risk. All participants had pre-existing cardiovascular disease or risk factors thereof. Four domains of cognitive function were tested at baseline and repeated during a follow-up period of 3.2 years. Results: Participants with higher NT-proBNP (≥450ng/l) had worse baseline cognitive function, including reaction time (mean difference high vs low group = 3.07 seconds, 95% confidence interval [CI] = 0.83 to 5.32), processing speed (-1.02 digits coded, 95% CI = -1.65 to -0.39), and immediate memory (-0.13 pictures remembered, 95% CI = -0.29 to 0.04). There was no significant difference in delayed memory (-0.14, 95% CI = -0.38 to 0.10) between the NT-proBNP groups. Participants with higher NT-proBNP had a steeper cognitive decline, including reaction time (mean annual change high vs low group = 0.60 seconds, 95% CI = 0.14 to 1.07), processing speed (-0.15 digits coded, 95% CI = -0.25 to -0.05), immediate memory (-0.05 pictures remembered, 95% CI = -0.09 to 0.00), and delayed memory (-0.05 pictures remembered, 95% CI = -0.11 to 0.01). Associations were independent of cardiovascular diseases and risks. Interpretation: Higher NT-proBNP associates with worse cognitive function and steeper cognitive decline, independent of cardiovascular diseases and risks. Further studies to unravel the underlying mechanisms are warranted.
    Annals of Neurology 08/2014; 76(2). DOI:10.1002/ana.24203 · 9.98 Impact Factor
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    ABSTRACT: Background: Hyperglycaemia during hospital admission is common in patients who are not known to have diabetes and is associated with adverse outcomes. The risk of subsequently developing type 2 diabetes, however, is not known. We linked a national database of hospital admissions with a national register of diabetes to describe the association between admission glucose and the risk of subsequently developing type 2 diabetes. Methods and findings: In a retrospective cohort study, patients aged 30 years or older with an emergency admission to hospital between 2004 and 2008 were included. Prevalent and incident diabetes were identified through the Scottish Care Information (SCI)-Diabetes Collaboration national registry. Patients diagnosed prior to or up to 30 days after hospitalisation were defined as prevalent diabetes and were excluded. The predicted risk of developing incident type 2 diabetes during the 3 years following hospital discharge by admission glucose, age, and sex was obtained from logistic regression models. We performed separate analyses for patients aged 40 and older, and patients aged 30 to 39 years. Glucose was measured in 86,634 (71.0%) patients aged 40 and older on admission to hospital. The 3-year risk of developing type 2 diabetes was 2.3% (1,952/86,512) overall, was <1% for a glucose ≤ 5 mmol/l, and increased to approximately 15% at 15 mmol/l. The risks at 7 mmol/l and 11.1 mmol/l were 2.6% (95% CI 2.5-2.7) and 9.9% (95% CI 9.2-10.6), respectively, with one in four (21,828/86,512) and one in 40 (1,798/86,512) patients having glucose levels above each of these cut-points. For patients aged 30-39, the risks at 7 mmol/l and 11.1 mmol/l were 1.0% (95% CI 0.8-1.3) and 7.8% (95% CI 5.7-10.7), respectively, with one in eight (1,588/11,875) and one in 100 (120/11,875) having glucose levels above each of these cut-points. The risk of diabetes was also associated with age, sex, and socio-economic deprivation, but not with specialty (medical versus surgical), raised white cell count, or co-morbidity. Similar results were obtained for pre-specified sub-groups admitted with myocardial infarction, chronic obstructive pulmonary disease, and stroke. There were 25,193 deaths (85.8 per 1,000 person-years) over 297,122 person-years, of which 2,406 (8.1 per 1,000 person-years) were attributed to vascular disease. Patients with glucose levels of 11.1 to 15 mmol/l and >15 mmol/l had higher mortality than patients with a glucose of <6.1 mmol/l (hazard ratio 1.54; 95% CI 1.42-1.68 and 2.50; 95% CI 2.14-2.95, respectively) in models adjusting for age and sex. Limitations of our study include that we did not have data on ethnicity or body mass index, which may have improved prediction and the results have not been validated in non-white populations or populations outside of Scotland. Conclusion: Plasma glucose measured during an emergency hospital admission predicts subsequent risk of developing type 2 diabetes. Mortality was also 1.5-fold higher in patients with elevated glucose levels. Our findings can be used to inform patients of their long-term risk of type 2 diabetes, and to target lifestyle advice to those patients at highest risk. Please see later in the article for the Editors' Summary.
    PLoS Medicine 08/2014; 11(8):e1001708. DOI:10.1371/journal.pmed.1001708 · 14.43 Impact Factor
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    ABSTRACT: Visit-to-visit blood pressure (BP) variability is associated with cognitive impairment. We assessed to what extent the association between BP variability and cognitive impairment is mediated by the association of BP lowering medication (BPLM) with both BP variability and cognition. We studied 5,606 participants from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). BP was measured every 3 months during 3.2 years; BP variability was defined as the SD of BP measurements during follow-up. Cognitive function was assessed at baseline and during follow-up using the Stroop test, Letter-Digit Coding test, and immediate and delayed Picture-Word Learning tests. Multivariate regression models were used with and without adjustments for BPLM to calculate the percentage to which BPLM mediated the association between BP variability and cognition. Participants taking calcium antagonists had a higher score in baseline Letter-Digit Coding test (mean difference (95% confidence interval (CI) 0.45 (0.06; 0.88). Participants taking beta-blockers had a steeper decline in Stroop test (additional change per year (95% CI) 0.40 (0.09; 0.70) and Letter-Digit Coding test (0.08 (-0.15; -0.02)). Furthermore, a steeper decline in Stroop test was found in participants taking renin-angiotensin system (RAS) inhibitors (0.50 (0.16; 0.85). Systolic BP variability was higher in participants taking beta-blockers and RAS inhibitors (mean difference in systolic BP variability in mm Hg (95% CI) 0.75 (0.45; 1.04) and 1.37 (1.04; 1.71) respectively). Participants taking diuretics, calcium antagonists, and RAS inhibitors had a higher diastolic BP variability (mean difference in diastolic BP variability in mm Hg (95% CI) 0.27 (0.04; 0.49), 0.37 (0.12; 0.62) and 0.65 (0.37; 0.93) SD, respectively). Beta estimates remained essentially the same when we adjusted for BPLM in the association of BP variability with cognitive function. The association between BP variability and cognitive impairment was not mediated by BPLM. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email:
    American Journal of Hypertension 07/2014; 10(4). DOI:10.1016/j.jalz.2014.05.1535 · 2.85 Impact Factor
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    ABSTRACT: Objective To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design Mendelian randomisation meta-analysis of 56 epidemiological studies. Participants 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Main outcome measures Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Results Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (−0.88 (−1.19 to −0.56) mm Hg), interleukin-6 levels (−5.2% (−7.8 to −2.4%)), waist circumference (−0.3 (−0.6 to −0.1) cm), and body mass index (−0.17 (−0.24 to −0.10) kg/m2). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). Conclusions Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.
    BMJ (online) 07/2014; 349. DOI:10.1136/bmj.g4164 · 17.45 Impact Factor
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    ABSTRACT: Background Statin therapy is widely used in the prevention and treatment of cardiovascular events and is associated with significant risk reductions. However, there is considerable variation in response to statin therapy both in terms of LDL cholesterol reduction and clinical outcomes. It has been hypothesized that genetic variation contributes importantly to this individual drug response. Methods and results We investigated the interaction between genetic variants and pravastatin or placebo therapy on the incidence of cardiovascular events by performing a genome-wide association study in the participants of the PROspective Study of Pravastatin in the Elderly at Risk for vascular disease–PHArmacogenetic study of Statins in the Elderly at risk (PROSPER/PHASE) study (n = 5244). We did not observe genome-wide significant associations with a clinically meaningful differential cardiovascular event reduction by pravastatin therapy. In addition, SNPs with p-values lower than 1 × 10−4 were assessed for replication in a case-only analysis within two randomized placebo controlled pravastatin trials, CARE (n = 711) and WOSCOPS (n = 522). rs7102569, on chromosome 11 near the ODZ4 gene, was replicated in the CARE study (p = 0.008), however the direction of effect was opposite. This SNP was not associated in WOSCOPS. In addition, none of the SNPs replicated significantly after correcting for multiple testing. Conclusions We could not identify genetic variation that was significantly associated at genome-wide level with a clinically meaningful differential event reduction by pravastatin treatment in a large prospective study. We therefore assume that in daily practice the use of genetic characteristics to personalize pravastatin treatment to improve prevention of cardiovascular disease will be limited.
    Atherosclerosis 07/2014; 235(1):58–64. DOI:10.1016/j.atherosclerosis.2014.04.009 · 3.99 Impact Factor
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    ABSTRACT: Objective: To compare the relationship between adiposity and prevalent diabetes across ethnic groups in the UK Biobank cohort and to derive ethnic-specific obesity cutoffs that equate to those developed in white populations in terms of diabetes prevalence. Research design and methods: UK Biobank recruited 502,682 U.K. residents aged 40-69 years. We used baseline data on the 490,288 participants from the four largest ethnic subgroups: 471,174 (96.1%) white, 9,631 (2.0%) South Asian, 7,949 (1.6%) black, and 1,534 (0.3%) Chinese. Regression models were developed for the association between anthropometric measures (BMI, waist circumference, percentage body fat, and waist-to-hip ratio) and prevalent diabetes, stratified by sex and adjusted for age, physical activity, socioeconomic status, and heart disease. Results: Nonwhite participants were two- to fourfold more likely to have diabetes. For the equivalent prevalence of diabetes at 30 kg/m(2) in white participants, BMI equated to the following: South Asians, 22.0 kg/m(2); black, 26.0 kg/m(2); Chinese women, 24.0 kg/m(2); and Chinese men, 26.0 kg/m(2). Among women, a waist circumference of 88 cm in the white subgroup equated to the following: South Asians, 70 cm; black, 79 cm; and Chinese, 74 cm. Among men, a waist circumference of 102 cm equated to 79, 88, and 88 cm for South Asian, black, and Chinese participants, respectively. Conclusions: Obesity should be defined at lower thresholds in nonwhite populations to ensure that interventions are targeted equitably based on equivalent diabetes prevalence. Furthermore, within the Asian population, a substantially lower obesity threshold should be applied to South Asian compared with Chinese groups.
    Diabetes Care 06/2014; 37(9). DOI:10.2337/dc13-2966 · 8.42 Impact Factor
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    Naveed Sattar ·
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    ABSTRACT: As is well known, diabetes rates continue to escalate worldwide, adding cost and disease burden to all health-care institutions. Over the last few years, however, a number of diabetes paradigms have been challenged, not least on the best methods to lessen or delay the development of co-morbidities, in particular cardiovascular disease (CVD) (i.e. targeting blood pressure, cholesterol, and smoking will do more than intensive glucose control). In addition, recent research has offered some hope to potentially reverse diabetes in motivated individuals, with resultant larger and longer trials of such interventions about to commence. This brief review summarizes these important recent developments and suggests that, while many new drugs are being added to the diabetes therapeutic armory, more could and should be done to target sustainable weight change in our patients for multiple health benefits.
    F1000 Prime Reports 06/2014; 6:42. DOI:10.12703/P6-42

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  • 2003-2015
    • University of Glasgow
      • • Institute of Cardiovascular and Medical Sciences
      • • School of Medicine
      Glasgow, Scotland, United Kingdom
    • University of Texas at San Antonio
      San Antonio, Texas, United States
    • University of Cambridge
      Cambridge, England, United Kingdom
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom
  • 2014
    • Wellcome Trust Sanger Institute
      Cambridge, England, United Kingdom
  • 2012
    • Leiden University Medical Centre
      • Department of Gerontology and Geriatrics
      Leiden, South Holland, Netherlands
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2009-2012
    • University of Bristol
      • • School of Experimental Psychology
      • • MRC Centre for Causal Analyses in Translational Epidemiology
      Bristol, England, United Kingdom
    • University of London
      Londinium, England, United Kingdom
  • 2006-2011
    • University of Aberdeen
      • Health Services Research Unit
      Aberdeen, Scotland, United Kingdom
  • 2007
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 2005
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 2002
    • West Georgia Obstetrics and Gynecology
      Georgetown, Georgia, United States
  • 1998
    • Copenhagen University Hospital Hvidovre
      • Department of Clinical Biochemistry
      Hvidovre, Capital Region, Denmark