Factors predicting cardiovascular events in statin-treated diabetic and non-diabetic patients with coronary atherosclerosis
Introduction
Atherosclerosis is a progressive disease. Eventually, it becomes aggressive and malignant, particularly in patients with type 2 diabetes mellitus (T2DM). As a consequence, atherosclerotic cardiovascular disease is the major cause of death and disability in the general population of industrialized countries, and is responsible for the majority of deaths in patients with T2DM [1].
Prevention of disability and death in these patients can be achieved by halting the progression of atherosclerosis. Antihyperglycemic treatment schedules have failed to reduce cardiovascular disease in patients with T2DM [2], [3]. Low-density lipoprotein (LDL) lowering therapy has been much more successful: statins have become a cornerstone in the treatment of atherosclerotic cardiovascular disease, in particular of coronary artery disease (CAD).
However, only about 30% of cardiovascular events observed with placebo treatment can be prevented by statins [4]. This means that two out of three complications still occur despite statin treatment; even if maximally tolerated doses are used in high risk patients such as those with acute coronary syndromes, only a further 16% of events are prevented. Among the very-high risk patients with both CAD and T2DM, residual risk is particularly unsatisfactory [5]. Statins therefore cannot be the sole solution.
The effect of statins on cardiovascular event reduction is closely related to their efficacy in lowering low-density lipoprotein cholesterol [4]. Intervention on other risk factors or pathophysiologic pathways may add to the beneficial effects of statins. Knowledge of the factors driving atherosclerosis in statin-treated patients should be a clue to a further reduction of cardiovascular events. Data from epidemiologic [6] and interventional [7], [8] studies point to a role for low high-density lipoprotein (HDL) cholesterol in cardiovascular disease progression. However, no observational data are available to discern which lipid factors predict cardiovascular events in statin-treated CAD patients under contemporary real-life conditions including interventional cardiology and cardiac surgery. Specifically, it is unknown which lipid risk factors or pathophysiologic pathways are most important in the very-high risk population of statin-treated patients with T2DM.
We therefore undertook an observational 6-year prospective cohort study enrolling diabetic and non-diabetic patients with angiographically proven CAD who received statins to elucidate the factors driving atherosclerosis progression in these patients.
Section snippets
Patients and basic study design
This is a prospective observational investigation on consecutive unselected patients undergoing coronary angiography for the evaluation of CAD. The design of this study has been described in detail earlier [9]. In brief, we enrolled 756 consecutive Caucasian patients referred to coronary angiography for routine evaluation of suspected or established stable CAD. Patients who had suffered myocardial infarctions or acute coronary syndromes within 3 months prior to the baseline angiography were not
Patient characteristics
Baseline data of our cohort were characteristic for a cohort of angiographied coronary patients, with a mean age of 63 ± 10 years, a preponderance of male gender (72.7%), and a high prevalence of hypertension (55.0%), history of smoking (62.9%) and T2DM (23.6%). Baseline characteristics of our patients with normal fasting glucose (NFG), impaired fasting glucose (IFG), and T2DM are summarized in Table 1.
Prospective study
Over a mean follow-up period of 5.6 ± 1.4 years, we recorded 161 first vascular events, which
Discussion
With our 6-year observational study we were able to identify the pattern of high triglycerides, small dense LDL, low HDL cholesterol and low apolipoprotein A1 as the paramount predictor of disease progression in statin-treated CAD patients. In particular, this pattern strongly predicted future cardiovascular events in patients with manifest T2DM.
Pathophyisologically, high triglycerides, low HDL cholesterol, low apolipoprotein A1, and small dense LDL are four different facets of a common
Conflict of interest
None declared.
Acknowledgements
The VIVIT Institute thanks Dr. Egmond Frommelt and the Innovationsstiftung of the Liechtenstein Global Trust (LGT) Bank (Bendern, Liechtenstein), Dr. Karl Josef Hier and the Peter Goop Stiftung (Vaduz, Liechtenstein), the Fachhochschule Dornbirn (Dornbirn, Austria), and the Institute for Clinical Chemistry at the Academic Teaching Hospital Feldkirch (Feldkirch, Austria) for providing us with generous research grants. We are grateful to Franz Rauch and the Vorarlberger Industriellenvereinigung
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