High risk cardiovascular disease: From insight to therapy

The last decades have witnessed tremendous progress in preventing and treating cardiovascular disease. Notably, the advent of statin therapy in the 1990s marks one of the victories of contemporary medicine. Yet, in spite of these successes, cardiovascular disease remains the leading cause of death and disability globally. Moreover, the trend of reduced mortality due to cardiovascular disease has flattened in recent years. Fortunately, there may be light at the end of the tunnel. Recent technological advances – most notably in the field of genetics – have enabled leaps in our understanding of the pathophysiological processes that lead to atherosclerosis, and have unveiled new therapeutic targets. This thesis aims to contribute to the translation of pathophysiological insights into improved diagnostic methods and therapies for patients with a high risk of cardiovascular disease. The objectives are threefold: 1. Illustrate how “top-down” population studies, combined with “bottom-up” mechanistic studies, can conjointly lead to a better understanding of the path from risk factor exposure to cardiovascular disease; 2. Illustrate how population studies can quantify the prevalence of specific manifestations of cardiovascular disease or risk factors, and how assessments of existing diagnostic methods can lead to more appropriate use of those methods; 3. Illustrate how more effective use of existing treatment options, combined with novel therapies enabled by rapid scientific advances, can lead to improved therapeutic options for high-risk cardiovascular disease patients

How common are foot problems among individuals with diabetes? Diabetic foot ulcers in the Dutch population.

Aims/hypothesis Contemporary data on diabetic foot ulcer prevalence are scarce. Most studies w ere conducted in the 1990s, reporting incidence rates of 1.9–2.6%. Since then the revalence of diabetes has doubled and the organisation of diabetes care has undergone major changes. Up-to-date data that quantify the occurrence of diabetic foot ulcers are required and could serve as baseline measures for future studies. Methods Individuals with diabetes (n = 81,793) were identified from the NIVEL (Netherlands institute for health services research) Primary Care Database, which contains data for standardised routine care and is representative of the Dutch population. The annual incidence rates of ulcers and other foot abnormalities were calculated using data collected between 2010 and 2013. To account for inaccuracies, incidence rates were calculated using: (1) only individuals with a documented foot examination; (2) all individuals; and (3) individuals with explicit documentation of present/absent foot ulceration. Results There were 412 individuals with documented ulceration during the registration period (0.50%). The annual incidence rate of foot ulcers was 0.34% (range 0.22–1.08%). Of those individuals with a documented foot examination, 14.6% had absent pedal pulsations, 17.3% had neuropathy and 10.1% had callus/pressure marks. Conclusions/interpretation The annual incidence rate of foot ulcers in the current study was lower than previously reported. This observation could reflect the efficacy of screening practices and an increased awareness among professionals and patients. Nevertheless, approximately one in every five diabetic individuals had at least one identifiable risk factor on foot examination. This signifies the importance of preventive screening. (aut. ref.

High daily insulin exposure in patients with type 2 diabetes is associated with increased risk of cardiovascular events

Aims Intensive glucose control, often involving insulin treatment, failed to improve cardiovascular outcomes in several clinical trials. Observational studies reported an association between insulin use and cardiovascular disease (CVD) risk. It has therefore been suggested that insulin adversely affects CVD risk. To investigate the feasibility of this hypothesis, we studied the association between insulin dose and CVD risk in type 2 diabetes. Methods A case-control study was conducted of new users of oral antidiabetics who were prescribed insulin, using the Dutch Pharmo database. Cases were hospitalized for a cardiovascular event (CVE) and matched 1:2 to patients who were not hospitalized for a CVE, by sex, age, duration of diabetes and type of oral antidiabetic. Patients were divided into tertiles according to mean daily insulin dose. Conditional logistic regression analyses were used to explore the association between insulin exposure and CVE risk. Results We included 836 patients (517 (62%) male, mean age 66 years). After adjusting for available potential confounders, including HbA1c and triglycerides, insulin exposure was positively related to CVE risk (odds ratios for high (≥53.0 U/day) and intermediate (24.3–52.9 U/day) vs. low exposure (≤24.2 U/day): 3.00 [95% confidence interval (CI) 1.70 to 5.28] and 2.03 [95% CI 1.17 to 3.52]. Conclusion Our findings are in line with the suggestion that high-dose insulin therapy adversely affects CVD risk, but need to be interpreted with caution due to the observational nature of the study. The role of particularly high-dose insulin in the progression of CVD warrants further investigation