Cerebral-placental-uterine ratio as novel predictor of late fetal growth restriction: prospective cohort study.

OBJECTIVE: Fetal growth restriction (FGR) is a major risk factor for stillbirth and most commonly arises from uteroplacental insufficiency. Despite clinical examination and third-trimester fetal biometry, cases of FGR often remain undetected antenatally. Placental insufficiency is known to be associated with altered blood flow resistance in maternal, placental and fetal vessels. The aim of this study was to evaluate the performance of individual and combined Doppler blood flow resistance measurements in the prediction of term small-for-gestational age and FGR. METHODS: This was a prospective study of 347 nulliparous women with a singleton pregnancy at 36 weeks' gestation in which fetal growth and Doppler measurements were obtained. Pulsatility indices (PI) of the uterine arteries (UtA), umbilical artery (UA) and fetal vessels were analyzed, individually and in combination, for prediction of birth weight < 10th , < 5th and < 3rd centiles. Doppler values were converted into centiles or multiples of the median (MoM) for gestational age. The sensitivities, positive and negative predictive values and odds ratios (OR) of the Doppler parameters for these birth weights at ∼ 90% specificity were assessed. Additionally, the correlations between Doppler measurements and other measures of placental insufficiency, namely fetal growth velocity and neonatal body fat measures, were analyzed. RESULTS: The Doppler combination most strongly associated with placental insufficiency was a newly generated parameter, which we have named the cerebral-placental-uterine ratio (CPUR). CPUR is the cerebroplacental ratio (CPR) (middle cerebral artery PI/UA-PI) divided by mean UtA-PI. CPUR MoM detected FGR better than did mean UtA-PI MoM or CPR MoM alone. At ∼ 90% specificity, low CPUR MoM had sensitivities of 50% for birth weight < 10th centile, 68% for < 5th centile and 89% for < 3rd centile. The respective sensitivities of low CPR MoM were 26%, 37% and 44% and those of high UtA-PI MoM were 34%, 47% and 67%. Low CPUR MoM was associated with birth weight < 10th centile with an OR of 9.1, < 5th centile with an OR of 17.3 and < 3rd centile with an OR of 57.0 (P < 0.0001 for all). CPUR MoM was also correlated most strongly with fetal growth velocity and neonatal body fat measures, as compared with CPR MoM or UtA-PI MoM alone. CONCLUSIONS: In this cohort, a novel Doppler variable combination, the CPUR (CPR/UtA-PI), had the strongest association with indicators of placental insufficiency. CPUR detected more cases of FGR than did any other Doppler parameter measured. If these results are replicated independently, this new parameter may lead to better identification of fetuses at increased risk of stillbirth that may benefit from obstetric intervention. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Incidence and prevalence of multiple sclerosis in the UK 1990-2010: a descriptive study in the General Practice Research Database.

OBJECTIVES: To estimate the incidence and prevalence of multiple sclerosis (MS) by age and describe secular trends and geographic variations within the UK over the 20-year period between 1990 and 2010 and hence to provide updated information on the impact of MS throughout the UK. DESIGN: A descriptive study. SETTING: The study was carried out in the General Practice Research Database (GPRD), a primary care database representative of the UK population. MAIN OUTCOME MEASURES: Incidence and prevalence of MS per 100 000 population. Secular and geographical trends in incidence and prevalence of MS. RESULTS: The prevalence of MS recorded in GPRD increased by about 2.4% per year (95% CI 2.3% to 2.6%) reaching 285.8 per 100 000 in women (95% CI 278.7 to 293.1) and 113.1 per 100 000 in men (95% CI 108.6 to 117.7) by 2010. There was a consistent downward trend in incidence of MS reaching 11.52 per 100 000/year (95% CI 10.96 to 12.11) in women and 4.84 per 100 000/year (95% CI 4.54 to 5.16) in men by 2010. Peak incidence occurred between ages 40 and 50 years and maximum prevalence between ages 55 and 60 years. Women accounted for 72% of prevalent and 71% of incident cases. Scotland had the highest incidence and prevalence rates in the UK. CONCLUSIONS: We estimate that 126 669 people were living with MS in the UK in 2010 (203.4 per 100 000 population) and that 6003 new cases were diagnosed that year (9.64 per 100 000/year). There is an increasing population living longer with MS, which has important implications for resource allocation for MS in the UK.

Effectiveness of statins in chronic kidney disease.

BACKGROUND: Previous studies show that statins reduce total cholesterol (TC) concentration by both 21% in primary prevention (PP) and secondary prevention (SP) in clinical trials and by ∼24% in the general population. There are few data about the efficacy of statins on TC concentration and cardiovascular (CV) outcome in patients with chronic kidney disease (CKD). We evaluated the reduction of TC concentration and subsequent risk of CV morbidity and mortality with statins in CKD patients. METHODS: A population-based cohort study using a record-linkage database in Tayside, Scotland. A total of 2369 patients who had a primary diagnosis of CKD from Scottish Morbidity Record data or biochemistry database (serum creatinine of 220 µmol/l or higher) and who had at least two separate TC measurements between 1993 and 2007 were studied. Patients were categorized into statin-exposed and statin-unexposed groups according to statin use status during the follow-up. They were also classified into PP (n = 1325) and SP (n = 1044) cohorts at the entry date. The main outcomes were TC concentration change from baseline, CV events [Antiplatelet Trialist's Collaboration (APTC)] and all-cause mortality during the follow-up. Cox regression models, in which statin use was a time-dependent variable, were employed to assess the risk of outcome and adjusted for other known confounders. RESULTS: Statin-associated TC concentrations decreased by 0.59 mmol/l (12%) in PP cohort and 0.56 mmol/l (13%) in SP cohort from 4.77 and 4.48 mmol/l at baselines, respectively. Statin use was associated with a reduced risk of APTC events, CV mortality or all-cause mortality in PP {adjusted hazard ratio (HR), 0.65 [95% confidence interval (CI) 0.48-0.88]; 0.73 (95% CI 0.52-0.98); 0.59 (95% CI 0.48-0.73)} and SP [adjusted HR, 0.66 (95% CI 0.52-0.84); 0.60 (95% CI 0.47-0.77); 0.56 (95% CI 0.47-0.68)], respectively. CONCLUSION: Statin use reduced TC concentrations by ∼13% in patients with CKD. Statins were protective of APTC events, CV mortality and all-cause mortality in patients with or without established CV disease.

Antiplatelet drug interactions.

Both laboratory studies in healthy volunteers and clinical studies have suggested adverse interactions between antiplatelet drugs and other commonly used medications. Interactions described include those between aspirin and ibuprofen, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), and the thienopyridine, clopidogrel, and drugs inhibiting CYP2C19, notably the proton pump inhibitors (PPI) omeprazole and esomeprazole. Other interactions between thienopyridines and CYP3A4/5 have also been reported for statins and calcium channel blockers. The ibuprofen/aspirin interaction is thought to be caused by ibuprofen blocking the access of aspirin to platelet cyclo-oxygenase. The thienopyridine interactions are caused by inhibition of microsomal enzymes that metabolize these pro-drugs to their active metabolites. We review the evidence for these interactions, assess their clinical importance and suggest strategies of how to deal with them in clinical practice. We conclude that ibuprofen is likely to interact with aspirin and reduce its anti-platelet action particularly in those patients who take ibuprofen chronically. This interaction is of greater relevance to those patients at high cardiovascular risk. A sensible strategy is to advise users of aspirin to avoid chronic ibuprofen or to ingest aspirin at least 2 h prior to ibuprofen. Clearly the use of NSAIDs that do not interact in this way is preferred. For the clopidogrel CYP2C19 and CYP3A4/5 interactions, there is good evidence that these interactions occur. However, there is less good evidence to support the clinical importance of these interactions. Again, a reasonable strategy is to avoid the chronic use of drugs that inhibit CYP2C19, notably PPIs, in subjects taking clopidogrel and use high dose H2 antagonists instead. Finally, anti-platelet agents probably interact with other drugs that affect platelet function such as selective serotonin reuptake inhibitors, and clinicians should probably judge patients taking such combination therapies as at high risk for bleeding.

The effects of lumiracoxib 100 mg once daily vs. ibuprofen 600 mg three times daily on the blood pressure profiles of hypertensive osteoarthritis patients taking different classes of antihypertensive agents.

AIMS: To examine whether the blood pressure (BP) profiles of lumiracoxib and high-dose ibuprofen differed in patients treated with different classes of antihypertensive medications. METHODS: A 4-week, multicentre, randomised, double-blind study has compared the effects of lumiracoxib 100 mg once daily (od) (n = 394) and ibuprofen 600 mg three times daily (tid) (n = 393) on ambulatory BP in osteoarthritis (OA) patients with controlled hypertension. Here, we present subgroup analyses for patients receiving different antihypertensive classes. The primary outcome was a comparison of the change in 24-h mean systolic ambulatory BP (MSABP) from baseline to week 4. Patients receiving angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) represented the largest subgroups receiving antihypertensive monotherapy. RESULTS: For patients receiving an ARB monotherapy, the least squares mean (LSM) 24-h MSABP at week 4 fell with lumiracoxib 100 mg od and increased with ibuprofen 600 mg tid, creating an estimated treatment difference of 8.1 mmHg in favour of lumiracoxib (p < 0.001). For patients receiving an ACEI and a beta-blocker monotherapy, the estimated treatment difference was 8.2 mmHg (p < 0.001) and 5.8 mmHg (p = 0.002) in favour of lumiracoxib respectively. These treatment differences were greater than observed in the overall population (5.0 mmHg in favour of lumiracoxib). In patients receiving diuretics or calcium channel blockers, treatment differences in MSABP were smaller and not statistically significant, although they remained in favour of lumiracoxib. CONCLUSION: Lumiracoxib 100 mg od resulted in less destabilisation of BP than high-dose ibuprofen 600 mg tid, and this effect was the greatest in subgroups treated with drugs blocking the renin-angiotensin system.

Association between allopurinol and mortality in heart failure patients: a long-term follow-up study.

AIMS: The aim of the study was to explore the long-term effect of allopurinol on mortality and cardiovascular hospitalisations in heart failure (HF) patients. METHODS: This is a population-based cohort study using a record-linkage database in Tayside, Scotland. A total of 4785 HF patients (4260 non-users, 267 incident users and 258 prevalent users) were studied between 1993 and 2002. RESULTS: Compared with non-users, low-dose users in the incident group had a significant increased risk of all-cause mortality, cardiovascular mortality and cardiovascular recurrence (adjusted HR, 1.60, 95%CI 1.26-2.03; 1.70, 1.29-2.23 and 1.44, 1.01-2.07). For the prevalent users, the adjusted HR were 1.27, 0.98-1.64; 1.43, 1.07-1.90 and 1.27, 0.91-1.76 respectively. There was no increased risk of outcome for high-dose users when compared with non-users (adjusted HR, 1.18, 0.84-1.66; 1.14, 0.76-1.71 and 1.36, 0.88-2.10 for the incident users, and 0.86, 0.64-1.15; 0.90, 0.64-1.26; and 1.27, 0.93-1.74 for the prevalent users respectively). High-dose allopurinol was associated with reduced risk of all-course mortality for prevalent users when compared with low-dose (adjusted HR 0.65, 95%CI 0.42-0.99). CONCLUSIONS: The prevalent high-dose allopurinol use had a lower risk of mortality than the prevalent low-dose use suggesting that allopurinol may be of benefit in HF patients.

Influenza but not pneumococcal vaccination protects against all-cause mortality in patients with COPD.

BACKGROUND: Influenza and pneumococcal vaccination are recommended in patients with chronic obstructive pulmonary disease (COPD). A recent study from Tayside found a reduced risk of all-cause mortality with vaccination in patients with COPD. The Health Improvement Network (THIN) database was used to test this hypothesis in a different data source. METHODS: The THIN database was searched for patients with COPD. Vaccination status against Pneumococcus and the annual influenza vaccination status were determined. Mortality rates were calculated in the periods December to March and April to November. Relative risks for the effect of vaccination on all-cause mortality were estimated by Poisson regression, adjusting for age, sex, year and serious co-morbidities. RESULTS: 177,120 patients with COPD (mean age 65 years) were identified, with a mean follow-up of 6.8 years between 1988 and 2006. Vaccination rates against influenza rose from <30% before 1995 to >70% in 2005 in patients aged 60 years or more. The cumulative vaccination rate against pneumonia rose from almost zero to 70% in patients aged 70 years or more over the same period. For all-cause mortality the adjusted relative risks associated with influenza vaccination were 0.59 (95% CI 0.57 to 0.61) during the influenza season and 0.97 (95% CI 0.94 to 1.00) outside the season in patients not vaccinated against pneumonia, and 0.30 (95% CI 0.28 to 0.32) and 0.98 (95% CI 0.96 to 1.11), respectively, in patients vaccinated against pneumonia. The relative risk associated with pneumococcal vaccination was >1 at all times of the year. CONCLUSIONS: Influenza but not pneumococcal vaccination was associated with a reduced risk of all-cause mortality in COPD.

Exercise blood pressure and endothelial dysfunction in hypertension.

BACKGROUND: Hypertensive patients with persistent endothelial dysfunction have adverse cardiovascular prognosis. However, current methods aimed to assess endothelial dysfunction in those patients who possess clinical applicability. We hypothesised that such individuals could potentially be identified by an exaggerated systolic blood pressure (BP) response to a submaximal exercise. METHODS: We studied 22 male patients with essential hypertension who were categorised into two age-matched groups depending on their exercise systolic BP (ExSBP) rise during the 3-min exercise step test; the exaggerated ExSBP group [hyper-responders (> or = 40 mmHg)] and the low ExSBP responder group [hypo-responders (< or = 20 mmHg)]. Eleven healthy volunteers matched for age were used as control. Clinic and daytime ambulatory BP were assessed after 14 days of anti-hypertensive treatment withdrawal, which were not significantly different between groups. Vascular reactivity in response to intra-arterial infusions of acetylcholine, N(G)-monomethyl-l-arginine (l-NMMA) and sodium nitroprusside was assessed using forearm venous occlusion plethysmography. RESULTS: The hyper-responder group had significantly less forearm vasodilatation to acetylcholine compared with the hypo-responder group [percentage change in the forearm blood flow 125 (17) vs. 260 (28), mean (SEM); p < 0.001]. Similarly, the vasoconstrictive response to l-NMMA was significantly impaired in the hyper-responder group in comparison to the hypo-responder group [-30 (2) vs. -45 (4); p < 0.05]. In contrast, the vascular response to sodium nitroprusside was not different between groups suggesting preserved endothelial-independent vasodilatation. CONCLUSIONS: Despite similar ambulatory and office BP, the exaggerated ExSBP group had significantly worse endothelial function compared with the low ExSBP responder group. This simple and non-invasive test may be useful in routine clinical practice to aid risk stratification in hypertensive patients.

The association between coeliac disease and cardiovascular disease.

BACKGROUND: Coeliac disease is more prevalent than was previously thought. The association between coeliac disease and cardiovascular outcome is not clear. AIM: To investigate whether coeliac disease patients have an increased risk of cardiovascular events. METHODS: A community-based cohort study using a record-linkage database. Three hundred and sixty-seven coeliac patients identified by a positive antiendomysial antibody test or a diagnosis with small bowel biopsy, and 5537 subjects who were tested and had a negative coeliac immunology, were included in the study. RESULTS: The crude rates of cardiovascular events were 9.5 per 1000 person-years (95% CI: 4.4-14.6) in the coeliac cohort and 8.9 per 1000 person-years (95% CI: 7.6-10.3) in the antiendomysial antibody-negative cohort. Compared with the antiendomysial antibody-negative cohort, the adjusted relative risk of cardiovascular events for coeliac cohort was 1.9 (95% CI: 1.00-3.60). When we excluded patients who had previous hospitalization for cardiovascular disease, the adjusted relative risk was 2.5 (95% CI: 1.22-5.01). The use of any cardiovascular drugs prior to and after entry to the study were 36% and 29% for the coeliac cohort (P = 0.05), and 34% and 26% for the antiendomysial antibody-negative cohort (P < 0.01). CONCLUSION: Our findings suggest that coeliac disease seems to be associated with an increased risk of cardiovascular outcome.

Impact on mortality following first acute myocardial infarction of distance between home and hospital: cohort study.

OBJECTIVE: To investigate the effect of distance between home and acute hospital on mortality outcome of patients experiencing an incident myocardial infarction (MI). DESIGN: Cohort study using a record linkage database. SETTING: Tayside, Scotland, UK. PATIENTS: 10,541 patients with incident acute MI between 1994 and 2003 were identified from Tayside hospital discharge data and from death certification data. MAIN OUTCOME MEASURES: MI mortality in the community, all-cause mortality in hospital and all-cause mortality during follow-up. RESULTS: 4133 subjects died following incident MI in the community (that is, were not hospitalised), 6408 patients survived to be hospitalised and 1010 of these (15.8%) died in hospital. Of 5398 discharged from hospital, 1907 (35.3%) died during a median of 3.2 years of follow-up. After adjustment for rurality and other known risk factors, distance between home and admitting hospital was significantly associated with increased mortality both before hospital admission (adjusted odds ratio (OR), 2.05, 95% CI 1.00 to 4.21 for >9 miles and 1.46, 1.09 to 1.95 for 3-9 miles when compared to <3 miles) and after hospitalisation (adjusted hazard ratio (HR) 1.90, 1.19 to 3.02 and 1.27, 0.96 to 1.68). However, there was no effect of distance on in-hospital mortality (adjusted OR 0.95, 0.45 to 2.03 and 1.02, 0.66 to 1.58). CONCLUSION: The distance between home and hospital of admission may predict mortality in subjects experiencing a first acute MI. This association was found both before and after hospitalisation. Further studies are needed to explore the reasons for this association. However these data provide support for policies that locate services for acute MI closer to where patients live.

Increasing prevalence and incidence of thyroid disease in Tayside, Scotland: the Thyroid Epidemiology Audit and Research Study (TEARS).

OBJECTIVE: We aimed to describe the changing incidence of thyroid disease in a population-based study in Tayside, Scotland (population 390 000) between 1994 and 2001. DESIGN: A retrospective, data-linkage, population-based study measuring the incidence and prevalence of thyroid disease. PATIENTS: All patients with newly diagnosed, treated and stable thyroid disease in Tayside were identified by electronic linkage of six datasets, including all regional biochemistry data, hospital admissions, deaths and a thyroid follow-up register. RESULTS: The overall prevalence of thyroid dysfunction has increased from 2.3% to 3.8% (1994-2001). The prevalence of ever having had hyperthyroidism increased from 0.86% to 1.26% in females and 0.17% to 0.24% in males (P < 0.0001 for both). The standardized incidence of hyperthyroidism increased from 0.68 to 0.87 per 1000 females/year, representing a 6.3% annual increase (P < 0.0001). The prevalence of primary hypothyroidism increased from 3.12% to 5.14% in females and 0.51% to 0.88% in males (P < 0.0001 for both). The standardized incidence of primary hypothyroidism did not change and varied between 3.90 and 4.89 per 1000 females/year over the 8 years. Incidence of hypothyroidism in males increased from 0.65 to 1.01 per 1000 males/year (P = 0.0017). Mean age at diagnosis of primary hypothyroidism declined in females from 1994 to 2001. CONCLUSIONS: The prevalence of primary hypothyroidism and previous hyperthyroidism has increased in Tayside, Scotland. This is partly due to an increasing incidence of disease, increased ascertainment and earlier diagnosis of disease. This will result in an increased workload for endocrinologists and general practitioners.

Treatment patterns of hypertension and dyslipidaemia in hypertensive patients at higher and lower risk of cardiovascular disease in primary care in the United Kingdom.

Few studies have investigated the presence of dyslipidaemia in hypertensive individuals. In addition, few data exist on the concurrent treatment of both conditions for the prevention of cardiovascular disease (CVD). This retrospective cohort study examined treatment patterns for hypertension and dyslipidaemia among hypertensive patients in UK primary care. We defined a population of patients aged > or =40 years from the UK General Practice Research Database. Hypertensive individuals with > or =3 additional cardiovascular risk factors (ARFs) were compared with a cohort comprising hypertensive patients with < or =2 ARFs. We analysed the prevalence of risk factors and the prevalence and incidence of treatment for hypertension, dyslipidaemia and for both conditions between January 1997 and December 2001. A total of 117 840 hypertensive patients were identified (23 655 with > or =3 ARFs, 94 185 with < or =2 ARFs) in 1997; in 2001, the number diagnosed as hypertensive was 133 683 (40 248 > or =3 ARFs, 93 435 < or =2 ARFs). The prevalence of antihypertensive treatment in the hypertensive patients with > or =3 ARFs increased during the study. In 2001, approximately one-third of hypertensive patients with > or =3 ARFs were not receiving antihypertensives. Among those patients who received such treatment, the majority received > or =2 separate agents in accordance with current guidelines. Treatment for concurrent hypertension and dyslipidaemia was initiated in <8% of patients with hypertension and > or =3 ARFs in each year. These findings demonstrate the under-recognition/undertreatment of cardiovascular risk factors in UK primary care among patients at risk of CVD.

Effectiveness of two statin prescribing strategies with respect to adherence and cardiovascular outcomes: observational study.

BACKGROUND: There is considerable evidence that statins can reduce cardiovascular events. Currently high-risk patients are treated to a target cholesterol concentration. An alternative prescribing strategy (the 'fire-and-forget' approach) would instead deploy low-dose statins more widely. It has been suggested that for the same cost this approach might prevent more cardiovascular events. We have compared the treat-to-target and fire-and-forget statin prescribing strategies with respect to adherence and cardiovascular outcomes. METHODS: We used a population-based record-linkage database containing several data sets linked by a unique patient identifier. We identified two cohorts of patients. Patients in the treat-to-target cohort were prescribed a statin, and subsequent measurement of their cholesterol was followed by upward titration of their statin dose if necessary. Patients in the fire-and-forget cohort were prescribed a statin, but no further cholesterol measurement was observed during the follow-up period. FINDINGS: Adherence to statin treatment in patients treated to target was significantly better than in patients treated on a fire-and-forget basis (adjusted odds ratio 2.51, 95%CI 2.26-2.78). We found a lower cardiovascular disease (CVD) event rate in patients treated to target than in fire-and-forget patients (hazard ratio of CVD or cardiovascular death 0.41 (0.35-0.48) even after adjustment was made for adherence and baseline CVD risk). INTERPRETATION: Our findings suggest that adherence to statins is worse in patients treated on a fire-and-forget basis than in patients treated to a target cholesterol concentration, and that this prescribing strategy is associated with worse cardiovascular outcomes.

Mortality and vascular outcomes in patients treated for thyroid dysfunction.

CONTEXT: There are limited studies describing mortality and morbidity in patients treated for hyperthyroidism, and no data exist for people with treated hypothyroidism. OBJECTIVE: The objective of the study was to describe all-cause mortality and vascular mortality and morbidity in patients after treatment for hyperthyroidism and hypothyroidism. DESIGN: This was a population-based cohort study from 1994 to 2001. SETTING: The study was conducted in Tayside, Scotland. PATIENTS: All patients were treated for thyroid dysfunction. INTERVENTION(S): Event rates among patients with thyroid dysfunction were compared with rates in the general population. We measured standardized mortality ratio and standardized incidence ratio (SIR). MAIN OUTCOME MEASURE(S): The primary outcome was all-cause mortality. The secondary outcome was serious vascular event, the composite end point of nonfatal myocardial infarction, nonfatal stroke, or vascular death. RESULTS: There were 15,889 primary hypothyroid and 3,888 hyperthyroid patients. There were 3,116,719 patient-years of follow-up in 524,152 subjects in the general population. No increase was found in all-cause mortality or serious vascular events in patients with treated hypothyroidism or hyperthyroidism. Nonfatal ischemic heart disease [SIR 1.23, 95% confidence interval (CI) 1.10-1.36] and dysrhythmias (SIR 1.32, 95% CI 1.11-1.57) were increased in treated hypothyroidism when adjusted for age, sex, diabetic status, and previous vascular disease. In treated stabilized hyperthyroidism, only the risk of dysrhythmias was increased (SIR 2.71, 95% CI 1.63-4.24). Risk of heart failure or cerebrovascular disease was not increased in either patient group. CONCLUSIONS: We found no increase in all-cause mortality in subjects with treated thyroid disease. However, there was increased risk of cardiovascular morbidity in patients with treated primary hypothyroidism and dysrhythmias in treated hyperthyroidism.

Impact on cardiovascular events of increasing high density lipoprotein cholesterol with and without lipid lowering drugs.

OBJECTIVE: To estimate the impact on cardiovascular events of changes in high density lipoprotein (HDL) adjusted for changes in total cholesterol. DESIGN: Cohort study based on a record linkage database. SETTING: Community study in Tayside, Scotland, UK. PATIENTS: 18,815 patients were identified for the study between 1989 and 2001. MAIN OUTCOME MEASURES: Cardiovascular events. RESULTS: 5510 patients taking lipid lowering treatment who had not been hospitalised previously for cardiovascular disease had 314 cardiovascular events recorded (9407 person years of follow up). Patients whose HDL rose by > 20% were less likely to have an event (23.5/1000 person years, 95% confidence interval (CI) 17.3 to 29.6) compared with patients whose HDL did not rise (42.6/1000 person years, 95% CI 35.5 to 49.7, adjusted relative risk 0.60, 95% CI 0.44 to 0.83). HDL change and cardiovascular outcome were not significantly associated among patients who had been hospitalised previously for cardiovascular disease or among patients who were not taking lipid lowering drugs. CONCLUSION: In this study a rise in HDL independently predicted reduced cardiovascular risk in patients taking lipid lowering treatment who had not been hospitalised previously for cardiovascular disease.