Clinical Pharmacology and Vascular Risk

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Abstract

Pharmacological treatment and several drugs of abuse have been associated with ischemic heart disease (IHD) and cerebrovascular diseases (CVD). However, there is a paucity of data on the independent risk of vascular disease (VD) associated with pharmacological treatment and no controlled trials demonstrating a reduction in risk with abstinence.

Information about IHD and CVD-related drug abuse is mainly limited to epidemiological studies focused on urban populations. The potential link between some pharmacological treatments (estrogen, some oncologic drugs and some atypical antipsychotics) and cerebrovascular adverse events was analyzed, but disagreement about an association persists. Drugs of abuse, including cocaine, amphetamines and heroin, have been associated with an increased vascular risk.

These drugs can cause abrupt changes in blood pressure, vasculitic-type changes, lead to embolization caused by infective endocarditis, and hemostatic and hematologic abnormalities that can result in increased blood viscosity and platelet aggregation. Long-term treatment strategies based on medication, psychological support, and outreach programs play an important role in treatment of drug dependency.

In these last years public interest in risk factors for VD has been constantly increasing and the successful identification and management of pharmacological treatment and drug abuse can be challenging. One of the major public health issues for the future will be to focus more on new vascular risk factor recognition and management.

The objective of this chapter is to review the relevance of IHD and CVD associated with various pharmacological treatments and drug abuse with focusing on ischemic disease.

This chapter reports the clinical evidence of this association and analyzes the experimental role of new drugs as a growing risk factor of VD with the hypothetical new association. In conclusion, in this chapter great attention is paid to evaluating the scientific and real evidence of cerebrovascular effect and drug use and abuse so as to identify a new groups of “modifiable” risk factors.

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Most cited references 60

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Antipsychotic drug use and mortality in older adults with dementia.

Daniel Anderson, Susan E Bronskill, Steven S. Gill … (2007)

Antipsychotic drugs are widely used to manage behavioral and psychological symptoms in dementia despite concerns about their safety. To examine the association between treatment with antipsychotics (both conventional and atypical) and all-cause mortality. Population-based, retrospective cohort study. Ontario, Canada. Older adults with dementia who were followed between 1 April 1997 and 31 March 2003. The risk for death was determined at 30, 60, 120, and 180 days after the initial dispensing of antipsychotic medication. Two pairwise comparisons were made: atypical versus no antipsychotic use and conventional versus atypical antipsychotic use. Groups were stratified by place of residence (community or long-term care). Propensity score matching was used to adjust for differences in baseline health status. A total of 27,259 matched pairs were identified. New use of atypical antipsychotics was associated with a statistically significant increase in the risk for death at 30 days compared with nonuse in both the community-dwelling cohort (adjusted hazard ratio, 1.31 [95% CI, 1.02 to 1.70]; absolute risk difference, 0.2 percentage point) and the long-term care cohort (adjusted hazard ratio, 1.55 [CI, 1.15 to 2.07]; absolute risk difference, 1.2 percentage points). Excess risk seemed to persist to 180 days, but unequal rates of censoring over time may have affected these results. Relative to atypical antipsychotic use, conventional antipsychotic use was associated with a higher risk for death at all time points. Sensitivity analysis revealed that unmeasured confounders that increase the risk for death could diminish or eliminate the observed associations. Information on causes of death was not available. Many patients did not continue their initial treatments after 1 month of therapy. Unmeasured confounders could affect associations. Atypical antipsychotic use is associated with an increased risk for death compared with nonuse among older adults with dementia. The risk for death may be greater with conventional antipsychotics than with atypical antipsychotics.

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Menopause and cardiovascular disease: the evidence.

G M C Rosano, C. Vitale, G Marazzi … (2007)

Menopause is a risk factor for cardiovascular disease (CVD) because estrogen withdrawal has a detrimental effect on cardiovascular function and metabolism. The menopause compounds many traditional CVD risk factors, including changes in body fat distribution from a gynoid to an android pattern, reduced glucose tolerance, abnormal plasma lipids, increased blood pressure, increased sympathetic tone, endothelial dysfunction and vascular inflammation. Many CVD risk factors have different impacts in men and women. In postmenopausal women, treatment of arterial hypertension and glucose intolerance should be priorities. Observational studies and randomized clinical trials suggest that hormone replacement therapy (HRT) started soon after the menopause may confer cardiovascular benefit. In contrast to other synthetic progestogens used in continuous combined HRTs, the unique progestogen drospirenone has antialdosterone properties. Drospirenone can therefore counteract the water- and sodium-retaining effects of the estrogen component of HRT via the renin-angiotensin-aldosterone system, which may otherwise result in weight gain and raised blood pressure. As a continuous combined HRT with 17beta-estradiol, drospirenone has been shown to significantly reduce blood pressure in postmenopausal women with elevated blood pressure, but not in normotensive women. Therefore, in addition to relieving climacteric symptoms, drospirenone/17beta-estradiol may offer further benefits in postmenopausal women, such as improved CVD risk profile.

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Sex-hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation (SWAN).

J Torrens, Sarah Brockwell, Rachel P Wildman … (2005)

Recent clinical trials have shifted attention away from estrogens and toward androgens and sex hormone-binding globulin (SHBG) as potential mediators of increasing cardiovascular (CV) risk in women at midlife. The correlation between reproductive hormones and CV risk factors was evaluated in a multiethnic (white, black, Hispanic, Chinese, and Japanese) sample of 3297 premenopausal and perimenopausal women. Testosterone and estradiol (E2) were evaluated along with SHBG and the free androgen index (FAI), the amount of testosterone not bound by SHBG. Low SHBG and high FAI were strongly and consistently related to elevated CV risk factors (higher insulin, glucose, and hemostatic and inflammatory markers and adverse lipids) even after controlling for body mass index (P<0.001 for all). Low levels of E2 were associated with elevated CV risk factors to a lesser degree. These observations were consistent across the 5 ethnic groups. Compared with whites, blacks had higher levels of SHBG and lower levels of FAI, and Chinese had lower levels of SHBG and higher levels of FAI. Low SHBG and high FAI are strongly associated with CV risk factors in racially diverse women, and thus, androgens likely play a role in the CV risk profile of perimenopausal women.

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Author and article information

Journal

Journal ID (nlm-ta): Open Neurol J

Journal ID (publisher-id): TONEUJ

Title: The Open Neurology Journal

Publisher: Bentham Open

ISSN (Electronic): 1874-205X

Publication date (Electronic): 15 June 2010

Publication date Collection: 2010

Volume: 4

Pages: 64-72

Affiliations

[1 ]Stroke Unit, Section of Neurology, C. Poma Hospital, Mantova, Italy

[2 ]UO Gravi Cerebrolesioni, Odpedale San Giovanni Battista, Foligno, Italy

[3 ]Stroke Unit, Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy

Author notes

[* ]Address correspondence to these authors at the Stroke Unit, Section of Neurology, Carlo Poma Hospital, Lago Paiolo n. 10, 46100 Mantova, Italy; Tel: +39 0376-201686; Fax: +39 0376-201969; E-mails: silvestrelli@ 123456hotmail.it , alessialanari@ 123456hotmail.com

Article

Publisher ID: TONEUJ-4-64

DOI: 10.2174/1874205X01004020064

PMC ID: 2923338

PubMed ID: 20721317

SO-VID: 5f1fa9ce-bb2d-42ee-8449-ba0514cac868

License:

This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

History

Date received : 11 May 2009

Date revision received : 21 December 2009

Date accepted : 22 December 2009

Clinical Pharmacology and Vascular Risk

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Abstract

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Stroke MRI

Most cited references 60

Antipsychotic drug use and mortality in older adults with dementia.

Menopause and cardiovascular disease: the evidence.

Sex-hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation (SWAN).

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