Cardiovascular events

The Oslo Trial (87) enrolled 785 male patients <50 years of age with DBP <110 mm Hg (15 Pa) and free of clinical evidence of cardiovascular disease. If the initial DBP was <100 mm Hg (13 Pa), there were no differences in mortaUty or cardiovascular events in the placebo- or dmg-treated groups. If the initial DBP was >100 mm Hg, then the incidence of cardiovascular disease was greater in the dmg-treated than in the placebo-treated group. 

Aromatase inhibitors are relatively well tolerated however have a number of distinct side effects are observed that stem from the state of estrogen deprivation induced by aromatase inhibitors. Side effects include hot flashes, joint and muscle aches, vasomotor symptoms and vaginal dryness. Variable effects of aromatase inhibitors on lipid levels have been observed. Trials comparing third generation aromatase inhibitors to tamoxifen have also repotted an increased risk of cardiovascular events in the group receiving aromatase inhibitors. 

In humans, biomarker responses to PPAR agonists by and large support possible antiatherosclerotic benefits, although recent clinical trial results have not proven conclusive. Further large-scale trials should help define the role of PPAR agonist therapy on cardiovascular events in at-risk populations. 

Our new appreciation of the role of inflammation in atherosclerosis shows the way for translation of these novel biological insights to clinical practice, for example by aiding the identification of individuals at risk of adverse cardiovascular events [5]. In this context, inflammatory biomarkers such as CRP merit rigorous consideration for inclusion in risk assessment strategies. In addition, these scientific advances provide a framework... 

Regardless of the initiating process or processes leading to the development of hypertension, the ultimate goal is to reduce the risk of cardiovascular events and minimize target organ damage. This clearly requires the early identification of risk factors and treatment of patients with hypertension. 

The treatment of elderly patients with hypertension, as well as those with isolated systolic hypertension, should follow the same approach as with other populations with the exception that lower starting doses may be warranted to avoid symptoms and with special attention paid to postural hypotension. This should include a careful assessment of orthostatic symptoms, measurement of blood pressure in the upright position, and caution to avoid volume depletion and rapid titration of antihypertensive therapy.2 In individuals with isolated systolic hypertension, the optimal level of diastolic pressure is not known, and although treated patients who achieve diastolic pressures less than 60 to 70 mm Hg had poorer outcomes in a landmark trial, their cardiovascular event rate was still lower than those receiving placebo.69... 

Oxidization of LDL-cholesterol is believed to play a significant role in the atherosclerotic process. The antioxidant vitamins, vitamin E and vitamin C, protect LDL cholesterol from oxidation. Evidence from observational and animal studies suggested that increased intake of antioxidant vitamins might inhibit the formation of atherosclerotic lesions and decrease the risk for cardiovascular events.40 However, several large, randomized, prospective studies found no beneficial effect of vitamin E or other antioxidants on cardiovascular outcomes in patients with IHD or IHD risk factors.41,42 Based on this evidence, current guidelines do not recommend supplementation with vitamin E or other antioxidants for the sole purpose of preventing cardiovascular events. 

Recent data suggest that COX-2 inhibitors, including rofe-coxib, valdecoxib, and celecoxib, may increase the risk for MI and stroke.47 There is also some evidence that the non-selective NSAIDs may increase the risk for cardiovascular events.47,48 Rofecoxib was withdrawn from the market in late 2004 because of safety concerns. The FDA requested the withdrawal of valdecoxib from the market in 2005. The FDA also asked the manufacturers of celecoxib and non-selective NSAIDs (prescription and over-the-counter) to include information about the potential adverse cardiovascular effects of these drugs in their product labeling. The cardiovascular risk with COX-2 inhibitors and NSAIDs may be greatest in patients with a history of, or with risk factors for, cardiovascular disease. The American Heart Association recommends that the use of COX-2 inhibitors be limited to low-dose, short-term therapy in patients for whom there is no appropriate alternative.48 Patients with cardiovascular disease should consult a clinician before using over-the-counter NSAIDs. 

Long-term desired outcomes are control of risk factors, prevention of additional cardiovascular events, and improvement in quality of life. 

The successful outcome in cholesterol management is to reduce cholesterol and triglycerides below the NCEP ATP III goals in an effort to alter the natural course of atherosclerosis and decrease future cardiovascular events. 

Topol EJ. Arthritis medicines and cardiovascular events house of coxibs. JAMA 2005 293 366-368. 

In March of 2007, the FDA announced that tegaserod maleate would be voluntarily withdrawn from the market because of information indicating an increased risk of serious cardiovascular events (myocardial infarction, unstable angina, and stroke). 

Methysergide is an ergotamine derivative that impacts central serotonin balance.51 It is reserved for use in migraineurs refractory to other agents, due to its significant adverse-effect profile. As an ergot compound, it is a vasoconstrictor that may worsen vascular dilatory reserves and precipitate cardiovascular events or ischemic stroke in those with... 

Poor sleep architecture and fragmented sleep secondary to OSA can cause excessive daytime sleepiness (EDS) and neu-rocognitive deficits. These sequelae can affect quality of life and work performance and may be linked to occupational and motor vehicle accidents. OSA is also associated with systemic disease such as hypertension, heart failure, and stroke.21-23 OSA is likely an independent risk factor for the development of hypertension.24 Further, when hypertension is present, it is often resistant to antihypertensive therapy. Fatal and non-fatal cardiovascular events are two- to threefold higher in male patients with severe OSA.25 OSA is associated with or aggravates biomarkers for cardiovascular disease, including C-reactive protein and leptin.26,27 Patients with sleep apnea often are obese and maybe predisposed to weight gain. Hence, obesity may further contribute to cardiovascular disease in this patient population. 

Nearly two-thirds of patients with DM will die of coronary heart disease (CHD). Interventions targeting smoking cessation, glycemic control, blood pressure control, lipid management, antiplatelet therapy, and lifestyle changes, including diet and exercise, can reduce the risk of cardiovascular events. Patients with diabetes should receive at least an aspirin daily unless contraindicated. Refer to appropriate chapters in the text concerning CHD. 

PCOS is associated with a three to seven times increased risk of developing type 2 diabetes.14 Patients diagnosed with PCOS should be screened for impaired glucose tolerance, diabetes, hypertension, and dyslipidemia.12 If any of these conditions are present, there is an increased risk of cardiovascular events. 

NSAIDs may accentuate the increased risk of cardiovascular events inherent in patients with RA. Increases in blood pressure and fluid retention may exacerbate existing cardiovascular disease. With the evidence associating COX-2 inhibitors with cardiovascular disease, clinicians must carefully evaluate the potential risks of NSAID therapy against the potential benefits.2 See Chap. 55 for additional discussion of NSAID therapy. 

NSAIDs are associated with gastrointestinal, renal, hepatic, and central nervous system toxicity and may increase blood pressure. NSAIDs that are selective for the cyclooxygenase-2 (COX-2) isozyme are less likely to cause gastrointestinal complications but may increase the risk of cardiovascular events. They are no more effective than nonselective NSAIDs. Selective agents should be reserved for patients at high risk of gastrointestinal complications and low risk for cardiovascular events. 

The advent of COX-2-selective inhibitors has led to unexpected results. By selectively inhibiting the COX-2 isoform, COX-2-selective NSAIDs increase the risk of cardiovascular events in certain patientsP COX-2 is responsible for the production of prostacyclin, a vasodilatory and antiplatelet substance. On the other hand, COX-1 controls the production of thromboxane A2, a vasoconstrictor and platelet aggregator. Selective inhibition of COX-2 results in decreased prostacyclin levels in the face of stable thromboxane A2 levels. An imbalance in the thromboxane A2 prostacyclin ratio ensues, which creates an environment that favors thrombosis. 

WL Nelson, FT Fraunfelder, JM Sills, JB Arrowsmith, JN Kuritsky. (1986). Adverse respiratory and cardiovascular events attributed to timolol ophthalmic solution. Am J Ophthalmol 102 606-611. 

Freeman DJ, Wilson V, McMahon AD, Packard CJ, Gaffney D. A polymorphism of the Cholesteryl Ester Transfer Protein (CETP) gene predicts cardiovascular events in the West of Scotland Coronary... 

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