HIV and the Heart: Difference between revisions

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(Created page with "<div align="right">'''''Tim P. van de Hoef, MD'''''</div> ==Case Study== ''A 42-year old male patient presents with ongoing fulminant retrosternal chest pain, radiating to t...")
 
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==Case Study==  
==Case Study==  
''A 42-year old male patient presents with ongoing fulminant retrosternal chest pain, radiating to the left shoulder and the jaw, with concomitant nausea. The patient awoke with these discerning complaints 21/2 hours ago, and there is no (recent) history of anginal symptoms. His medical history includes human immunodeficiency virus seropositivity since his 24<sup>th</sup>, for which he since successfully receives chronic combined antiretroviral therapy with Truvada (tenofovir/emtricitabine), ritonavir, and atazanavir, with undetectable viral loads. In the presence of hypercholesterolemia, further medication includes ezetemibe solotherapy, since statins were not tolerated. The electrocardiogram shows ST-segment elevation in the anterior precordial leads, and the patient is diagnosed with anterior wall acute myocardial infarction. Emergency coronary angiography is performed without delay, revealing a thrombotic occlusion of the left anterior descending coronary artery. Manual thrombus aspiration and subsequent stent implantation is performed successfully. In addition to lifelong aspirin treatment, and, despite revascularization guideline recommendation, the patient is post-treated with clopidogrel instead of prasugrel or ticagrelor for the first year following the acute myocardial infarction.''  
''A 42-year old male patient presents with ongoing fulminant retrosternal chest pain, radiating to the left shoulder and the jaw, with concomitant nausea. The patient awoke with these discerning complaints 21/2 hours ago, and there is no (recent) history of anginal symptoms. His medical history includes human immunodeficiency virus seropositivity since his 24<sup>th</sup>, for which he since successfully receives chronic combined antiretroviral therapy with Truvada (tenofovir/emtricitabine), ritonavir, and atazanavir, with undetectable viral loads. In the presence of hypercholesterolemia, further medication includes ezetemibe solotherapy, since statins were not tolerated. The electrocardiogram shows ST-segment elevation in the anterior precordial leads, and the patient is diagnosed with anterior wall acute myocardial infarction. Emergency coronary angiography is performed without delay, revealing a thrombotic occlusion of the left anterior descending coronary artery. Manual thrombus aspiration and subsequent stent implantation is performed successfully. In addition to lifelong aspirin treatment, and, despite revascularization guideline recommendation, the patient is post-treated with clopidogrel instead of prasugrel or ticagrelor for the first year following the acute myocardial infarction.''  


==Introduction==
==Introduction==
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==Modifiable risk factors==
==Modifiable risk factors==
Risk factors that comprise modifiable targets for therapeutic strategies include hypertension, dyslipidemia, diabetes, and smoking. Importantly, the prevalence of these traditional risk factors is increased in HIV-positive populations (PMID: 23369416). Compared with the general population, HIV-infected populations in particular have a higher smoking prevalence, and have a diet high in saturated fat. Evidence has accumulated that HIV-infected patients in general have a more atherogenic lipid spectrum, putting them at particular high risk for CVD (PMID: 23369416, 21587343). However, the relative contribution of each traditional risk factor for CVD risk within a patient is comparable in HIV-infected and uninfected populations, irrespective of HIV-infection status (PMID: 21587343). As such, although the risk factor prevalence is increased in HIV-infected populations, it likely does not at itself explain the increased risk of CVD in this population, and, therefore, several HIV-related factors need to be taken into consideration.
Risk factors that comprise modifiable targets for therapeutic strategies include hypertension, dyslipidemia, diabetes, and smoking. Importantly, the prevalence of these traditional risk factors is increased in HIV-positive populations (PMID: 23369416). Compared with the general population, HIV-infected populations in particular have a higher smoking prevalence, and have a diet high in saturated fat. Evidence has accumulated that HIV-infected patients in general have a more atherogenic lipid spectrum, putting them at particular high risk for CVD (PMID: 23369416, 21587343). However, the relative contribution of each traditional risk factor for CVD risk within a patient is comparable in HIV-infected and uninfected populations, irrespective of HIV-infection status (PMID: 21587343). As such, although the risk factor prevalence is increased in HIV-infected populations, it likely does not at itself explain the increased risk of CVD in this population, and, therefore, several HIV-related factors need to be taken into consideration.


==Antiretroviral therapy effects==
==Antiretroviral therapy effects==
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===Immune dysfunction and immune activation===
===Immune dysfunction and immune activation===
Several studies have indicated that immune dysfunction is associated with CVD risk among HIV-infected patients. CD4+ T-cell counts of <500/IL have been associated with an increase in cardiovascular events, independent of traditional CVD risk factors or ART, carrying an additive risk comparable with that of smoking or sub-optimally treated LDL cholesterol levels (PMID: 20597691). CD4+ T-cell counts of <200/IL were associated with an increased risk of AMI, which was comparable in magnitude to the risk imposed by traditional CVD risk factors (PMID: 20827215). Consistently, episodic CD4+ cell count-guided ART is associated with a substantial increase in risk for AMI compared with continuous ART, indicating an important role of viral load and immune dysfunction for the extent of CVD risk (PMID: 17135583). Moreover, several studies have shown a decrease in non-AIDS related events following the start of ART, and a notable increase in CVD events in patients with incomplete immune recovery following start of ART (PMID: 18781885, 18476292). In addition, the risk of AMI was recently shown to be significantly increased in patients with a recent episode of immune dysfunction defined as CD4 count <200 or HIV-RNA count of >500 copies (PMID: 22112603). It can therefore be acknowledged that (residual) compromise of immune function is an important determinant of risk for CVD as well.
Several studies have indicated that immune dysfunction is associated with CVD risk among HIV-infected patients. CD4+ T-cell counts of <500/IL have been associated with an increase in cardiovascular events, independent of traditional CVD risk factors or ART, carrying an additive risk comparable with that of smoking or sub-optimally treated LDL cholesterol levels (PMID: 20597691). CD4+ T-cell counts of <200/IL were associated with an increased risk of AMI, which was comparable in magnitude to the risk imposed by traditional CVD risk factors (PMID: 20827215). Consistently, episodic CD4+ cell count-guided ART is associated with a substantial increase in risk for AMI compared with continuous ART, indicating an important role of viral load and immune dysfunction for the extent of CVD risk (PMID: 17135583). Moreover, several studies have shown a decrease in non-AIDS related events following the start of ART, and a notable increase in CVD events in patients with incomplete immune recovery following start of ART (PMID: 18781885, 18476292). In addition, the risk of AMI was recently shown to be significantly increased in patients with a recent episode of immune dysfunction defined as CD4 count <200 or HIV-RNA count of >500 copies (PMID: 22112603). It can therefore be acknowledged that (residual) compromise of immune function is an important determinant of risk for CVD as well.




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==Prevention of CVD in HIV-infected patients==
==Prevention of CVD in HIV-infected patients==
As a corollary of the aforementioned interplay of CVD risk factors and HIV-infection/–therapy, it may be appreciated that prevention of CVD in HIV-positive patients should be emphasized, especially in the light of the contemporary life expectancy of this patient population. In general, cardiovascular therapy guidelines aimed at prevention of CVD in HIV-patients follow those for the general population, although some HIV-related factors must be taken into consideration (PMID: 18257770).  
As a corollary of the aforementioned interplay of CVD risk factors and HIV-infection/–therapy, it may be appreciated that prevention of CVD in HIV-positive patients should be emphasized, especially in the light of the contemporary life expectancy of this patient population. In general, cardiovascular therapy guidelines aimed at prevention of CVD in HIV-patients follow those for the general population, although some HIV-related factors must be taken into consideration (PMID: 18257770).  
Special emphasis should focus upon the identification and treatment of dyslypidemia, which is frequently present in HIV-infected patients, and which is known to occur in reponse to the start of (c)ART therapy, with a particular association with PIs (PMID: 17460226) and first generation NRTIs (PMID: 23369416). Therefore, assessment of lipid status, especially triglycerides, should be performed prior to the start of cART therapy, at 3-6 months after initiation of therapy, and at least yearly in the absence of abnormalities. A special point of care lies within lipid-lowering therapy in concomitance with cART treatment, because of the possibility of interaction between statins and for example PIs and NNRTIs (PMID: 23369416). The primary mode of interaction is seen through the cytochrome P450 (CYP) pathway. PIs mainly inhibit CYP, and could therefore lead to toxicity of statins as these drugs are most frequently metabolized through particular CYP pathways. NNRTIs are associated with CYP induction, leading to impairment of statin efficacy. Statins not or only mildly associated with CYP interactions include rosuvastatine and pravastatin, and may therefore be considered in HIV-infected patients on cART. More novel statins, such as pitavastatin, without CYP interaction have not yet been evaluated in this setting. Ezetemibe, which is not metabolized through the CYP pathway, may be considered in addition to statin therapy or as stand-alone therapy when statin therapy leads to unendured side effects. Nonetheless, statin therapy should be tailored to the specific situation and side effects or inefficacy of agents may necessitate statin or cART agent switch along the way. Especially when cART leads to a subsequent severe dyslipidemia, switching to another cART combination may be considered (PMID: 23369416). However, no clinical trials have been performed on this subject, and therefore the best approach remains patient-tailored. Moreover, in the light of the complex interplay between all CVD risk factors discussed in the previous paragraphs, it is important to note that the actual role of statin therapy in primary prevention in HIV-infected patients has not been established to date. Nonetheless, the evidence to date indicates a very important role of dyslipidemia in the CVD-risk associated with HIV-infection and –therapy, and optimal medical therapy should be pursued.
Special emphasis should focus upon the identification and treatment of dyslypidemia, which is frequently present in HIV-infected patients, and which is known to occur in reponse to the start of (c)ART therapy, with a particular association with PIs (PMID: 17460226) and first generation NRTIs (PMID: 23369416). Therefore, assessment of lipid status, especially triglycerides, should be performed prior to the start of cART therapy, at 3-6 months after initiation of therapy, and at least yearly in the absence of abnormalities. A special point of care lies within lipid-lowering therapy in concomitance with cART treatment, because of the possibility of interaction between statins and for example PIs and NNRTIs (PMID: 23369416). The primary mode of interaction is seen through the cytochrome P450 (CYP) pathway. PIs mainly inhibit CYP, and could therefore lead to toxicity of statins as these drugs are most frequently metabolized through particular CYP pathways. NNRTIs are associated with CYP induction, leading to impairment of statin efficacy. Statins not or only mildly associated with CYP interactions include rosuvastatine and pravastatin, and may therefore be considered in HIV-infected patients on cART. More novel statins, such as pitavastatin, without CYP interaction have not yet been evaluated in this setting. Ezetemibe, which is not metabolized through the CYP pathway, may be considered in addition to statin therapy or as stand-alone therapy when statin therapy leads to unendured side effects. Nonetheless, statin therapy should be tailored to the specific situation and side effects or inefficacy of agents may necessitate statin or cART agent switch along the way. Especially when cART leads to a subsequent severe dyslipidemia, switching to another cART combination may be considered (PMID: 23369416). However, no clinical trials have been performed on this subject, and therefore the best approach remains patient-tailored. Moreover, in the light of the complex interplay between all CVD risk factors discussed in the previous paragraphs, it is important to note that the actual role of statin therapy in primary prevention in HIV-infected patients has not been established to date. Nonetheless, the evidence to date indicates a very important role of dyslipidemia in the CVD-risk associated with HIV-infection and –therapy, and optimal medical therapy should be pursued.
In addition, smoking cessation should be actively pursued in patients with HIV, because of its high prevalence and associated increase in CVD risk in this patient population, as well as the significant benefit of smoking cessation (PMID: 21251183). The recent smoking cessation guidelines consequently indentified the HIV-infected population as and important target population for smoking cessation therapy, both interms of counseling as well as medical therapeutic strategies (PMID: 18617085).
In addition, smoking cessation should be actively pursued in patients with HIV, because of its high prevalence and associated increase in CVD risk in this patient population, as well as the significant benefit of smoking cessation (PMID: 21251183). The recent smoking cessation guidelines consequently indentified the HIV-infected population as and important target population for smoking cessation therapy, both interms of counseling as well as medical therapeutic strategies (PMID: 18617085).
In the presence of hypertension, renin angiotensin system blockers are considered first choice owing to their global protective effects on kidney function, glucose metabolism, and the vasculature in general (PMID: 23369416).
In the presence of hypertension, renin angiotensin system blockers are considered first choice owing to their global protective effects on kidney function, glucose metabolism, and the vasculature in general (PMID: 23369416).
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Clinical outcome after revascularization (predominantly for ACS) is similar for HIV-infected and non-infected populations, regardless of whether revascularization is performed percutaneously or surgically (PMID: 16537777, 18288976). HIV-infected patients, however, do remain at increased risk for recurrent ACS during follow-up (PMID: 20965887), which is importantly associated with persistently elevated lipid spectra.
Clinical outcome after revascularization (predominantly for ACS) is similar for HIV-infected and non-infected populations, regardless of whether revascularization is performed percutaneously or surgically (PMID: 16537777, 18288976). HIV-infected patients, however, do remain at increased risk for recurrent ACS during follow-up (PMID: 20965887), which is importantly associated with persistently elevated lipid spectra.


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!Key Points:
!Key Points:
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*The increased risk for cardiovascular disease predominantly results in an early occurrence of acute myocardial infarction, for which coronary revascularization is associated with good outcome, although recurrent ischemic events are more common in HIV-infected patients than in the general non-infected population.
*The increased risk for cardiovascular disease predominantly results in an early occurrence of acute myocardial infarction, for which coronary revascularization is associated with good outcome, although recurrent ischemic events are more common in HIV-infected patients than in the general non-infected population.
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==References==
<biblio>
#PMID: 16878047
#PMID: 20467289
#PMID: 21587343
</biblio>
NiloferT
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