Søren Rasmussen

Diabetes Patients Requiring Glucose-Lowering Therapy and Nondiabetics With a Prior Myocardial Infarction Carry the Same Cardiovascular Risk A Population Study of 3.3 Million People

Background— Previous studies reveal major differences in the estimated cardiovascular risk in diabetes mellitus, including uncertainty about the risk in young patients. Therefore, large studies of well-defined populations are needed. Methods and Results— All residents in Denmark ≥30 years of age were followed up for 5 years (1997 to 2002) by individual-level linkage of nationwide registers. Diabetes patients receiving glucose-lowering medications and nondiabetics with and without a prior myocardial infarction were compared. At baseline, 71 801 (2.2%) had diabetes mellitus and 79 575 (2.4%) had a prior myocardial infarction. Regardless of age, age-adjusted Cox proportional-hazard ratios for cardiovascular death were 2.42 (95% confidence interval [CI], 2.35 to 2.49) in men with diabetes mellitus without a prior myocardial infarction and 2.44 (95% CI, 2.39 to 2.49) in nondiabetic men with a prior myocardial infarction (P=0.60), with nondiabetics without a prior myocardial infarction as the reference. Results for women were 2.45 (95% CI, 2.38 to 2.51) and 2.62 (95% CI, 2.55 to 2.69) (P=0.001), respectively. For the composite of myocardial infarction, stroke, and cardiovascular death, the hazard ratios in men with diabetes only were 2.32 (95% CI, 2.27 to 2.38) and 2.48 (95% CI, 2.43 to 2.54) in those with a prior myocardial infarction only (P=0.001). Results for women were 2.48 (95% CI, 2.43 to 2.54) and 2.71 (95% CI, 2.65 to 2.78) (P=0.001), respectively. Risks were similar for both diabetes types. Analyses with adjustments for comorbidity, socioeconomic status, and prophylactic medical treatment showed similar results, and propensity score–based matched-pair analyses supported these findings. Conclusions— Patients requiring glucose-lowering therapy who were ≥30 years of age exhibited a cardiovascular risk comparable to nondiabetics with a prior myocardial infarction, regardless of sex and diabetes type. Therefore, requirement for glucose-lowering therapy should prompt intensive prophylactic treatment for cardiovascular diseases.

Persistent Use of Evidence-Based Pharmacotherapy in Heart Failure Is Associated With Improved Outcomes

Background— Undertreatment with recommended pharmacotherapy is a common problem in heart failure and may influence prognosis. We studied initiation and persistence of evidence-based pharmacotherapy in 107 092 patients discharged after first hospitalization for heart failure in Denmark from 1995 to 2004. Methods and Results— Prescriptions of dispensed medication and mortality were identified by an individual-level linkage of nationwide registers. Inclusion was irrespective of left ventricular function. Treatment with renin-angiotensin inhibitors (eg, angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers), &bgr;-blockers, spironolactone, and statins was initiated in 43%, 27%, 19%, and 19% of patients, respectively. Patients who did not initiate treatment within 90 days of discharge had a low probability of later treatment initiation. Treatment dosages were in general only 50% of target dosages and were not increased during long-term treatment. Short breaks in therapy were common, but most patients reinitiated treatment. Five years after initiation of treatment, 79% patients were still on renin-angiotensin inhibitors, 65% on &bgr;-blockers, 56% on spironolactone, and 83% on statins. Notably, multiple drug treatment and increased severity of heart failure was associated with persistence of treatment. Nonpersistence with renin-angiotensin inhibitors, &bgr;-blockers, and statins was associated with increased mortality with hazard ratios for death of 1.37 (95% CI, 1.31 to 1.42), 1.25 (95% CI, 1.19 to 1.32), 1.88 (95% CI, 1.67 to 2.12), respectively. Conclusions— Persistence of treatment was high once medication was started, but treatment dosages were below recommended dosages. Increased severity of heart failure or increased number of concomitant medications did not worsen persistence, but nonpersistence identified a high-risk population of patients who required special attention. A focused effort on early treatment initiation, appropriate dosages, and persistence with the regimen is likely to provide long-term benefit.

Women with acute coronary syndrome are less invasively examined and subsequently less treated than men

AIMS To investigate if gender bias is present in todays setting of an early invasive strategy for patients with acute coronary syndrome in Denmark (population 5 million). METHODS AND RESULTS We identified all patients admitted to Danish hospitals with acute coronary syndrome in 2005-07 (9561 women and 16 406 men). Cox proportional hazard models were used to estimate the gender differences in coronary angiography (CAG) rate and subsequent revascularization rate within 60 days of admission. Significantly less women received CAG (cumulative incidence 64% for women vs. 78% for men, P < 0.05), with a hazard ratio (HR) of 0.68 (95% CI 0.65-0.70, P < 0.0001) compared with men. The difference was narrowed after adjustment for age and comorbidity, but still highly significant (HR 0.82, 95% CI 0.80-0.85, P < 0.0001). Revascularization after CAG was less likely in women with an HR of 0.68 (95% CI 0.66-0.71, P < 0.0001) compared with men. More women (22%) than men (10%) (P < 0.0001) had no significant stenosis on their coronary angiogram. However, after adjustment for the number of significant stenoses, age, and comorbidity women were still less likely to be revascularized (HR 0.91, 95% CI 0.87-0.95, P < 0.0001). CONCLUSION Women with ACS are approached in a much less aggressively invasive way and receive less interventional treatment than men even after adjusting for differences in comorbidity and number of significant stenoses.

Mortality after acute myocardial infarction according to income and education

Objective: To study how income and educational level influence mortality after acute myocardial infarction (AMI). Design and setting: Prospective analysis using individual level linkage of registries in Denmark. Participants: All patients 30–74 years old hospitalised for the first time with AMI in Denmark in 1995–2002. Main outcome measures: Relative risk (RR) of 30 day mortality and long term mortality (31 days until 31 December 2003) associated with income (adjusted for education) or educational level (adjusted for income) and further adjusted for sex, age, civil status, and comorbidity. Results: The study identified 21 391 patients 30–64 years old and 16 169 patients 65–74 years old. The 30 day mortality was 7.0% among patients 30–64 years old and 15.9% among those 65–74 years old. Among patients surviving the first 30 days, the long term mortality was 9.9% and 28.3%, respectively. The adjusted RR of 30 day mortality and long term mortality among younger patients with low compared with high income was 1.54 (95% confidence interval 1.36 to 1.79) and 1.65 (1.45 to 1.85), respectively. The RR of 30 day and long term mortality among younger patients with low compared with high education was 1.24 (1.03 to 1.50) and 1.33 (1.11 to 1.59), respectively. The RR of 30 day and long term mortality among older patients with low compared with high income was 1.27 (1.15 to 1.41) and 1.38 (1.27 to 1.50), respectively. Older high and low education patients did not differ in mortality. Conclusion: This study shows that both educational level and income substantially and independently affect mortality after AMI, indicating that each indicator has specific effects on mortality and that these indicators are not interchangeable.

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1–11) among men with the ADH1B·1/1 genotype compared to 7.5 drinks (95% CI: 6.4–8.7) among men with the ADH1B·1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7–5.7) among men with the ADH1B·1/1 genotype compared to men with the ADH1B·1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1–1.8) among men with the ADH1C·1/2 genotype and 1.4 (95% CI: 1.0–1.9) among men with the ADH1B·2/2 genotype, compared with men with the ADH1C·1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1B·1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

Use of statins and beta-blockers after acute myocardial infarction according to income and education

Objective: To study the initiation of and long-term refill persistency with statins and beta-blockers after acute myocardial infarction (AMI) according to income and education. Design and setting: Linkage of individuals through national registers of hospitalisations, drug dispensation, income and education. Participants: 30 078 patients aged 30–74 years surviving first hospitalisation for AMI in Denmark between 1995 and 2001. Main outcome measures: Initiation of statin or beta-blocker treatment (out-patient claim of prescriptions within 6 months of discharge) and refill persistency (first break in treatment lasting at least 90 days, and re-initiation of treatment after a break). Results: When simultaneously estimating the effect of income and education on initiation of treatment, the effect of education attenuated and a clear income gradient remained for both drugs. Among patients aged 30–64 years, high income (adjusted hazard ratio (HR) 1.27; 95% confidence interval (CI) 1.19–1.35) and medium income (HR 1.13; 95% CI 1.06–1.20) was associated with initiation of statin treatment compared with low income. The risk of break in statin treatment was lower for patients with high (HR 0.73; 95% CI 0.66–0.82) and medium (HR 0.82; 95% CI 0.74–0.92) income compared with low income, whereas there was a trend in the opposite direction concerning a break in beta-blocker treatment. There was no gradient in re-initiation of treatment. Conclusion: Patients with low compared with high income less frequently initiated preventive treatment post-AMI, had worse long-term persistency with statins, but tended to have better persistency with beta-blockers. Low income by itself seems not to be associated with poor long-term refill persistency post-AMI.

Influence of smoking and alcohol consumption on admissions and duration of hospitalization.

BACKGROUND Previous studies have linked smoking and alcohol consumption to a considerable disease burden and large healthcare expenditures. However, findings from studies based on individual level data are sparse and inconclusive. Our objective was to assess the association between alcohol consumption, smoking and patterns of hospitalization, defined as admission and duration of hospitalization. METHODS The study was based on 12 698 men and women, aged 20 years or more, enrolled in the Copenhagen City Heart Study. We related smoking and alcohol to hospital admission from any cause, smoking- and alcohol-related diseases and duration of hospitalization in a two-part random effects model. RESULTS Smoking status was strongly associated with admission and duration of hospitalization. For smoking-related admissions, odds ratios (OR) of 2.77 (95% CI 2.13-3.59) in men and 6.30 (95% CI 4.80-8.26) in women were observed among smokers of >20 g/day compared to never-smokers. For any admission (excl. smoking-related causes), corresponding ORs were 1.32 (95% CI 1.15-1.51) and 1.80 (95% CI 1.58-2.06), respectively. In men, a U-shaped association between alcohol consumption and risk of admission was found, both regarding any admission and admissions due to alcohol-related diseases. Alcohol was associated with alcohol-related admissions in women but not with duration of hospitalization. CONCLUSIONS Smoking was associated with increased risk of hospital admission and duration of hospitalization. A U-shaped relation was observed for alcohol consumption and risk of hospitalization in men, but no effect on duration was observed. In women, however, alcohol consumption was only vaguely associated with admission and duration of hospitalization.

Prognostic information in administrative co-morbidity data following coronary artery bypass grafting

OBJECTIVES The aim of this study was to evaluate the prognostic information obtainable from administrative data with respect to 30-day mortality following coronary artery bypass grafting (CABG) and to compare it with the European System for Cardiac Operative Risk Evaluation (EuroSCORE) recorded in a clinical database. METHODS We used a co-morbidity index calculated from administrative data in the Danish National Patient Register by means of all admissions 1 year prior to CABG. In addition, each CABG was categorised as being isolated or not, and acute or not. The prognostic power of the co-morbidity index was compared to that achieved using EuroSCORE from a clinical database comprising information on all patients treated with CABG in Denmark. The outcome was all-cause mortality within 30 days after CABG and the prognostic power was evaluated using logistic regression analyses. RESULTS We identified 20078 patients treated with CABG from 2000 to 2007 with a complete registration of the total additive EuroSCORE in the clinical database. The co-morbidity index carried significant prognostic information regarding 30-day mortality (c-statistic 0.81). The prognostic power of the co-morbidity index was equal to that of the EuroSCORE (c-statistic 0.79). CONCLUSIONS A standard co-morbidity index based on administrative data as well as on clinical data has proven equally useful for prediction of mortality amongst CABG patients.