Steven Grinspoon

Harvard University, Cambridge, Massachusetts, United States

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Publications (266)1985.43 Total impact

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    ABSTRACT: Context: HIV patients are at increased risk for cardiometabolic disease secondary to depot-specific alterations in adipose function, but mechanisms remain poorly understood. Objective: The endoribonuclease Dicer has been linked to modulation of brown and white adipocyte differentiation. We previously demonstrated that Dicer-knockout mice undergo transformation of brown adipose tissue (BAT) to white adipose tissue (WAT) and develop a lipodystrophic phenotype. We hypothesized reduced Dicer and BAT gene expression from non-lipomatous subcutaneous (SC) fat among HIV patients with a lipodystrophic phenotype. Design: 18 HIV (9 with and without lipodystrophic changes in fat distribution, characterized by excess dorsocervical adipose tissue [DCAT]) and 9 non-HIV subjects underwent punch biopsy of abdominal SC fat to determine expression of Dicer and other adipose-related genes. Results: HIV subjects with long duration antiretroviral use demonstrated excess DCAT vs. non-HIV subjects (9.8±1.0 vs. 6.6±0.8cm(2), P=0.02) with similar BMI. Dicer expression was decreased in abdominal SC fat of HIV vs. non-HIV (4.88 [1.91, 11.93] vs.17.69 [10.72, 47.91], P=0.01), as were PGC1α, ZIC1, PRDM16, DIO2, and HSP60 (all P≤0.03). Moreover, expression of Dicer (2.49 [0.02, 4.88] vs. 11.20 [4.83, 21.45], P=0.006), brown fat [PGC1α (P=0.002), ZIC1 (P=0.004), LHX6 (P=0.03), PRDM16 (P=0.0008), PAT2 (P=0.008), P2RX5 (P=0.02)], beige fat [TMEM26 (P=0.004), CD137 (P=0.008)] and other genes [DIO2 (P=0.002), leptin (P=0.003), HSP60 (P=0.0004)] was further decreased in abdominal SC fat comparing HIV subjects with vs. without excess DCAT. Downregulation of Dicer in the abdominal SC fat correlated with downregulation of all brown and beige fat genes (all P≤0.01). Conclusion: Our results demonstrate dysfunctional SC adipose tissue marked by reduced Dicer in relationship to downregulation of brown and beige fat related genes in lipodystrophic HIV patients and may provide a novel mechanism for metabolic dysregulation. A strategy to increase "browning" of WAT may improve cardiometabolic health in HIV.
    No preview · Article · Jan 2016 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Plasma branched-chain amino acids (BCAA) are elevated in obesity and associated with increased cardiometabolic risk. β-Aminoisobutyric acid (B-AIBA), a recently identified small molecule metabolite, is associated with decreased cardiometabolic risk. Therefore, we investigated the association of BCAA and B-AIBA with each other and with detailed body composition parameters, including abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). A cross-sectional study was carried out with lean ( n 15) and obese ( n 33) men and women. Detailed metabolic evaluations, including measures of body composition, insulin sensitivity and plasma metabolomics were completed. Plasma BCAA were higher (1·6 ( se 0·08) (×10 7 ) v. 1·3 ( se 0·06) (×10 7 ) arbitrary units; P = 0·005) in obese v. lean subjects. BCAA were positively associated with VAT ( R 0·49; P = 0·0006) and trended to an association with SAT ( R 0·29; P = 0·052). The association between BCAA and VAT, but not SAT, remained significant after controlling for age, sex and race on multivariate modelling ( P < 0·05). BCAA were also associated with parameters of insulin sensitivity (Matsuda index: R −0·50, P = 0·0004; glucose AUC: R 0·53, P < 0·001). BCAA were not associated with B-AIBA ( R −0·04; P = 0·79). B-AIBA was negatively associated with SAT ( R −0·37; P = 0·01) but only trended to an association with VAT ( R 0·27; P = 0·07). However, neither relationship remained significant after multivariate modelling ( P > 0·05). Plasma B-AIBA was associated with parameters of insulin sensitivity (Matsuda index R 0·36, P = 0·01; glucose AUC: R −0·30, P = 0·04). Plasma BCAA levels were positively correlated with VAT and markers of insulin resistance. The results suggest a possible complex role of adipose tissue in BCAA homeostasis and insulin resistance.
    Preview · Article · Jan 2016
  • Jennifer M Gilbert · Kathleen V Fitch · Steven K Grinspoon
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    ABSTRACT: HIV infection is associated with increased cardiovascular disease (CVD), and increased rates of myocardial infarction and stroke have been observed in HIV-infected individuals. After traditional risk factors that are more common among people living with HIV infection (such as smoking and diabetes) are accounted for, the excess risk for CVD persists. Recent studies suggest that increased immune activation and inflammation may contribute to excess risk for CVD in the context of HIV infection. Imaging studies in the HIV-infected population have found inflamed, noncalcified plaque that is vulnerable to rupture. Statin therapy may represent a potentially useful primary prevention strategy for CVD in HIV-infected individuals, as this class of drugs lowers lipid levels and may simultaneously reduce immune activation and inflammation. REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) is a large, multicenter study funded by the National Institutes of Health. REPRIEVE will test whether pitavastatin, a newer statin that does not have substantial interactions with antiretroviral drugs, can prevent vascular events over time among HIV-infected individuals who do not have known CVD. This study is now open to enrollment at sites throughout the United States and abroad and will hopefully provide definitive data on this important question.
    No preview · Article · Dec 2015 · Topics in antiviral medicine
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    ABSTRACT: Context: Increased circulating free fatty acids (FFA) have been proposed to contribute to insulin resistance in obesity. Short-term studies have investigated the effects of acipimox, an inhibitor of hormone sensitive lipase, on glucose homeostasis, but longer term studies have not been performed. Objective: To test the hypothesis that long term treatment with acipimox would reduce FFA and improve insulin sensitivity among nondiabetic, insulin resistant obese subjects. Design, setting, patients, and intervention: At an academic medical center, 39 obese men and women were randomized to acipimox 250 mg thrice-daily vs. identical placebo for six months. Main outcome measures: plasma lipids, insulin sensitivity, adiponectin, and mitochondrial function via assessment of the rate of post-exercise phosphocreatine recovery (PCr) on (31)P-magnetic resonance spectroscopy as well as muscle mitochondrial density and relevant muscle gene expression Results: Fasting glucose decreased significantly in acipimox-treated individuals (effect size -6mg/dL, p=0.02), in parallel with trends for reduced fasting insulin (effect size -6.8 μU/mL, p=0.07) and HOMA-IR (effect size -1.96, p=0.06) and significantly increased adiponectin (effect size +668 ng/mL, p=0.02). Acipimox did not affect insulin-stimulated glucose uptake, as assessed by euglycemic, hyperinsulinemic clamp. Effects on muscle mitochondrial function and density, and relevant gene expression were not seen. Conclusion: These data shed light on the long term effects of FFA reduction on insulin sensitivity, other metabolic parameters, and muscle mitochondrial function in obesity. Reduced FFA achieved by acipimox improved fasting measures of glucose homeostasis, lipids and adiponectin, but had no effect on mitochondrial function, mitochondrial density, or muscle insulin sensitivity.
    No preview · Article · Dec 2015 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: Objective: Circulating oxidized low-density lipoprotein (oxLDL) levels are elevated in HIV-infected patients and have been associated with subclinical atherosclerosis. Statins have been shown to reduce plaque on coronary computed tomography angiography (cCTA) in HIV-infected individuals. Thus, we investigated the effect of statins on serum oxLDL levels and the relationship between changes in oxLDL and coronary atherosclerosis on cCTA in patients with HIV. Design: We previously conducted a 12-month randomized, placebo-controlled trial with atorvastatin in 40 HIV-infected patients on stable antiretroviral therapy with subclinical coronary atherosclerosis and low-density lipoprotein (LDL)-cholesterol less than 130 mg/dl. Methods: In the current analysis, patients underwent cCTA and measurements of serum oxLDL, sCD14, sCD163, lipoprotein phospholipase-A2, and fasting lipids including direct LDL at baseline and end of the study. Results: Nineteen patients were randomized to atorvastatin and 21 patients to placebo. Serum oxLDL decreased -22.7% (95% CI -28.7 to -16.7) in the atorvastatin group and increased 7.5% (95% CI -3.3 to 18.4) in the placebo group (P < 0.0001). Change in oxLDL significantly correlated with changes in noncalcified plaque volume, total plaque volume, positively remodeled plaque, and low attenuation plaque. The association between changes in oxLDL and noncalcified plaque volume was independent of the baseline 10-year Framingham risk, direct LDL, CD4 cell count, and viral load. Conclusion: Statins lower oxLDL levels in HIV-infected patients, and reductions in oxLDL are related to improvements in coronary atherosclerosis, independent of traditional cardiovascular risk factors. Reductions in oxLDL may be one mechanism through which statins exert beneficial effects on reducing atherosclerosis in HIV-infected individuals.
    No preview · Article · Nov 2015 · AIDS (London, England)
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    ABSTRACT: Objective: To investigate differences in subclinical coronary atherosclerotic plaque and markers of immune activation among HIV-infected and non-HIV-infected women categorized by degree of ovarian reserve and menopause status. Design: Cross-sectional evaluation. Methods: Seventy-four women (49 HIV-infected, 25 non-HIV-infected) without known cardiovascular disease (CVD) were classified as premenopausal, premenopausal with reduced ovarian reserve, or postmenopausal based on menstrual history and antimullerian hormone (AMH) levels. Participants underwent contrast-enhanced coronary computed tomography angiography and immune phenotyping. Comparisons in coronary atherosclerotic plaque burden and immune markers were made between the HIV-infected and non-HIV-infected women overall and within the HIV-infected and non-HIV-infected women by reproductive classification group. Results: Among the overall group of HIV-infected women, the women with reduced ovarian reserve (undetectable AMH) had a higher prevalence of coronary atherosclerotic plaque (52 versus 6%, P = 0.0007) and noncalcified plaque (48 versus 6%, P = 0.002), as well as higher levels of log sCD163 (P = 0.0004) and log MCP-1 (P = 0.006), compared with the premenopausal women with measurable AMH. Furthermore, reduced ovarian reserve in the HIV-infected group related to noncalcified plaque, controlling for traditional CVD risk factors (P = 0.04) and sCD163 (P = 0.03). Conclusion: HIV-infected women with reduced ovarian reserve have increased subclinical coronary atherosclerotic plaque compared with premenopausal women in whom AMH is measurable. This relationship holds when controlling for CVD risk factors (including age) and immune activation. Our findings demonstrate that reduced ovarian reserve may contribute to CVD burden in HIV-infected women and support a comprehensive assessment of CVD risk prior to completion of menopause in this population.
    No preview · Article · Oct 2015 · AIDS
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    ABSTRACT: Since the publication of the first issue of this journal in November 2005, our understanding of the endocrine system has evolved, with the identification of novel hormones and novel endocrine roles for previously identified molecules. Here, we have asked six of our Advisory Board Members to comment on how these insights have led to the recognition that many organs and tissues that were not widely considered part of the classic endocrine system in the past have important endocrine functions.
    No preview · Article · Sep 2015 · Nature Reviews Endocrinology
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    ABSTRACT: Little is known about renin-angiotensin-aldosterone system (RAAS) activation in relationship to visceral adipose tissue (VAT) accumulation in HIV-infected patients, a population at significant risk for insulin resistance and other metabolic disease. Twenty HIV and ten non-HIV-infected subjects consumed a standardized low sodium or liberal sodium diet, to stimulate or suppress the RAAS, respectively. RAAS parameters were evaluated in response to each diet and a graded angiotensin II infusion. Further analyses were performed after groups were substratified by median VAT measured by MRI. Aldosterone concentrations during the low sodium diet were higher in HIV than non-HIV-infected subjects(13.8 [9.7, 30.9] vs. 9.2 [7.6, 13.6]ng/dL,P=0.03) and increased across groups stratified by VAT(8.5 [7.1, 12.8], 9.2 [8.1, 21.5], 11.4 [9.4, 13.8], 27.2 [13.0, 36.9] ng/dL in non-HIV-infected without increased VAT, non-HIV-infected with increased VAT, HIV-infected without increased VAT, HIV-infected with increased VAT, respectively, overall trend P=0.02). Under this condition, plasma renin activity(3.50 [2.58, 4.65] vs. 1.45 [0.58, 2.33]ng/ml/hr, P=0.002) was higher among the HIV-infected subjects with vs. without increased VAT. Differences in the suppressibility of PRA by graded angiotensin infusion were seen stratifying by VAT among the HIV-infected group(P < 0.02 at each dose). In addition, aldosterone(P=0.007) was an independent predictor of insulin resistance in multivariate modeling, controlling for VAT and adiponectin. These data suggest excess RAAS activation in relationship to visceral adiposity in HIV-infected patients that may independently contribute to insulin resistance. Mineralocorticoid blockade may have therapeutic potential to reduce metabolic complications in HIV-infected patients with increased visceral adiposity.
    No preview · Article · Jun 2015 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: HIV-infected patients have a high risk of myocardial infarction. We aimed to assess the ability of statin treatment to reduce arterial inflammation and achieve regression of coronary atherosclerosis in this population.
    No preview · Article · Feb 2015 · The Lancet HIV
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    ABSTRACT: Some intestinal microbiota-generated metabolites of phosphatidylcholine are recognized to be proatherogenic. As the HIV population is vulnerable to cardiovascular disease and can develop intestinal dysbiosis associated with systemic inflammation, we investigated the novel relationship between microbiota-derived metabolites of phosphatidylcholine and coronary atherosclerosis in HIV. One hundred and fifty-five HIV-infected and 67 non-HIV-infected individuals without known history of cardiovascular disease were previously recruited to assess coronary plaque by computed tomography angiography. In the current study, we evaluate whether serum choline, trimethylamine (TMA), or trimethylamine-N-oxide (TMAO) levels are associated with plaque features. Young, asymptomatic HIV-infected patients (age 47 ± 7 years) demonstrated significantly higher prevalence of plaque (53 vs. 35%, P = 0.01) and number of total plaque segments (1.8 ± 2.5 vs. 1.2 ± 2.2, P = 0.03) when compared with well matched noninfected individuals with similar comorbidities. TMA was significantly associated with calcium score (r = 0.22, P = 0.006), number of total (r = 0.20, P = 0.02) and calcified (r = 0.18, P = 0.03) plaque segments, and calcium plaque volume (r = 0.19, P = 0.02) and mass (r = 0.22, P = 0.009) in the HIV cohort only. In multivariate modeling among HIV-infected patients, TMA remained significantly associated with calcium score (P = 0.008), number of total (P = 0.005) and calcified (P = 0.02) plaque segments, and calcium plaque volume (P = 0.01) and mass (P = 0.007), independent of Framingham risk score. In contrast, there was no association of TMAO to coronary plaque features in either cohort. A link between TMA and atherosclerosis has not previously been established. The current study suggests that TMA may be a nontraditional risk factor related to the number of plaque segments and severity of calcified plaque burden in HIV.
    Full-text · Article · Jan 2015 · AIDS (London, England)
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    Ahmed Tawakol · Steven K Grinspoon
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    ABSTRACT: HIV disease, left inadequately treated, leads to an inexorable decline in immune function resulting in AIDS and ultimately in death from opportunistic infections. However, advances in treatment of HIV have resulted in a dramatic reduction in AIDS-related mortality.1 With the widespread use of highly active antiretroviral therapy (HAART), HIV infection has been transformed to a chronic disease associated with long-term viral suppression but at the cost of an increase in atherothrombotic diseases.2,3 Hence currently there is substantial interest in developing a better understanding of the mechanisms underlying the increased risk of atherothrombosis in HIV disease.While HIV infection is characterized by a decline of peripheral blood CD4+ T cells, a paradoxical chronic immune activation of T cells and monocytes is routinely seen in virally suppressed HIV disease.4-6 Multiple studies in HIV-infected individuals show that this persistently heightened state of immune activation likely contrib ...
    Preview · Article · Dec 2014 · Journal of Nuclear Cardiology
  • Takara L. Stanley · Steven K. Grinspoon
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    ABSTRACT: Increased visceral adipose tissue (VAT) is associated with reductions in endogenous GH secretion, possibly as a result of hyperinsulinemia, increased circulating free fatty acid, increased somatostatin tone, and reduced ghrelin. Reduced GH may, in turn, further exacerbate visceral fat accumulation because of decreased hormone sensitive lipolysis in this depot. Data from multiple populations demonstrate that both reduced GH and increased VAT appear to contribute independently to dyslipidemia, increased systemic inflammation, and increased cardiovascular risk. The reductions in GH in states of visceral adiposity are characterized by reduced basal and pulsatile GH secretion with intact pulse frequency. Treatment with GH releasing hormone (GHRH) provides a means to reverse these abnormalities, increasing endogenous basal and pulsatile GH secretion without altering pulse frequency. This review describes data from HIV-infected individuals and individuals with general obesity showing that treatment with GHRH significantly reduces visceral fat, ameliorates dyslipidemia, and reduces markers of cardiovascular risk. Further research is needed regarding long term efficacy and safety of this treatment modality.
    No preview · Article · Dec 2014 · Growth Hormone & IGF Research
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    ABSTRACT: Human immunodeficiency virus (HIV) infection is associated with increased risk of myocardial infarction (MI). The use of aspirin for primary and secondary MI prevention in HIV infection has not been extensively studied. We performed a cross-sectional study of 4037 patients infected with HIV and 36 338 demographics-matched control patients in the Partners HealthCare System HIV cohort. We developed an algorithm to ascertain rates of nonepisodic acetylsalicylic acid (ASA) use using medication and electronic health record free text data. We assessed rates of ASA use among HIV-infected and HIV-uninfected (negative) patients with and without coronary heart disease (CHD). Rates of ASA use were lower among HIV-infected compared with HIV-uninfected patients (12.4% vs 15.3%, P < .001), with a relatively greater difference among patients with ≥2 CHD risk factors (22.1% vs 42.4%, P < .001). This finding was present among men and among patients in the 30-39 and 40-49 age groups. Among patients with prevalent CHD using ASA for secondary prevention, rates of ASA use were also lower among HIV-infected patients compared with HIV-uninfected patients (51.6% vs 65.4%, P < .001). Rates of ASA use were lower among HIV-infected patients compared with controls, with a greater relative difference among those with elevated CHD risk and those with known CHD. Further studies are needed to investigate the optimal strategies for ASA use among patients infected with HIV.
    Full-text · Article · Dec 2014 · Open Forum Infectious Diseases
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    ABSTRACT: Individuals infected with human immunodeficiency virus (HIV) have decreased high-density lipoprotein (HDL)-cholesterol and increased cardiovascular disease (CVD). Reverse cholesterol transport from macrophages may be inhibited by HIV and contribute to increased CVD. Human studies have not investigated longitudinal effects of HIV and antiretroviral therapy (ART) on cholesterol efflux. Subjects with acute HIV infection were randomized to ART or not. Cholesterol efflux capacity was determined ex vivo after exposure of murine macrophages to apolipoprotein B-depleted patient sera obtained at baseline and after 12 weeks. After 12 weeks, HIV RNA decreased most in subjects randomized to ART. Available data on cholesterol demonstrated that efflux capacity from Abca1(+/+) macrophages was increased most by sera obtained from ART-treated subjects (20.5% ± 5.0% to 24.3 % ± 6.9%, baseline to 12 weeks, P = .007; ART group [n = 6] vs 18.0 % ± 3.9% to 19.1 % ± 2.9%, baseline to 12 weeks, P = .30; untreated group [n = 6] [P = .04 ART vs untreated group]). Change in HIV RNA was negatively associated with change in Abca1(+/+) macrophage cholesterol efflux (r = - 0.62, P = .03), and this finding remained significant (P = .03) after controlling for changes in HDL-cholesterol, CD4(+) cells, and markers of monocyte or macrophage activation. In subjects acutely infected with HIV, ATP-binding cassette transporter A1-mediated cholesterol efflux was stimulated to a greater degree over time by apolipoprotein B-depleted serum from subjects randomized to ART. The improvement in cholesterol efflux capacity is independently related to reduction in viral load.
    Full-text · Article · Dec 2014 · Open Forum Infectious Diseases
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    ABSTRACT: Background: Heightened immune activation among human immunodeficiency virus (HIV)-infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and soluble CD14 (sCD14), and monocyte chemoattractant protein 1 (CCL2) with subclinical atherosclerosis among men with and those without HIV infection in the Multicenter AIDS Cohort Study. Methods: We performed noncontrast computed tomography on 906 men (566 HIV-infected men and 340 HIV-uninfected men), 709 of whom also underwent coronary computed tomographic angiography. Associations between each biomarker and the prevalence of coronary plaque, the prevalence of stenosis of ≥50%, and the extent of plaque were assessed by logistic and linear regression, adjusting for age, race, HIV serostatus, and cardiovascular risk factors. Results: Levels of all biomarkers were higher among HIV-infected men, of whom 81% had undetectable HIV RNA, and were associated with lower CD4(+) T-cell counts. In the entire population and among HIV-infected men, higher biomarker levels were associated with a greater prevalence of coronary artery stenosis of ≥50%. Higher sCD163 levels were also associated with greater prevalences of coronary artery calcium, mixed plaque, and calcified plaque; higher CCL2 levels were associated with a greater extent of noncalcified plaque. Conclusions: sCD163, sCD14, and CCL2 levels were elevated in treated HIV-infected men and associated with atherosclerosis. Monocyte activation may increase the risk for cardiovascular disease in individuals with HIV infection.
    No preview · Article · Oct 2014 · The Journal of Infectious Diseases
  • Markella V Zanni · Judith Schouten · Steven K Grinspoon · Peter Reiss
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    ABSTRACT: The lives of individuals infected with HIV who have access to combination antiretroviral therapy (cART) are substantially prolonged, which increases the risk of developing non-AIDS comorbidities, including coronary heart disease (CHD). In Europe and the USA, individuals with HIV infection have a ∼1.5-fold increased risk of myocardial infarction relative to uninfected individuals. In Africa, the relative risk of myocardial infarction is unknown, but broadened access to life-extending cART suggests that rates of CHD will rise in this and other resource-constrained regions. Atherogenesis in HIV is affected by complex interactions between traditional and immune risk factors. cART has varied, regimen-specific effects on metabolic risk factors. Overall, cART seems to lessen proatherogenic immune activation, but does not eliminate it even in patients in whom viraemia is suppressed. Current strategies to decrease the risk of CHD in individuals infected with HIV include early initiation of cART regimens with the fewest metabolic adverse effects, and careful management of traditional CHD risk factors throughout treatment. Future strategies to prevent CHD in patients with HIV infection might involve the use of HIV-tailored CHD risk-prediction paradigms and the administration of therapies alongside cART that will further decrease proatherogenic HIV-specific immune activation.
    No preview · Article · Oct 2014 · Nature Reviews Cardiology
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    ABSTRACT: Objective: To compare rates of intracerebral hemorrhage (ICH) in HIV-infected and uninfected individuals in a large clinical care cohort and to assess risk factors associated with ICH. Methods: We identified incident ICH in HIV-infected and uninfected control cohorts from the Partners Health Care system using ICD-9-CM codes. We constructed Cox proportional hazards models to estimate adjusted hazard ratios for HIV infection and other predictors of ICH. Results: The incidence rate of ICH was 2.29 per 1,000 person-years in HIV-infected individuals compared with 1.23 per 1,000 person-years in uninfected individuals, with an unadjusted incidence rate ratio of 1.85 (95% confidence interval 1.37-2.47, p < 0.001). In a multivariable model, HIV infection was independently associated with a higher hazard of ICH, although its effect diminished with increasing age. Female sex was associated with a lower hazard of ICH in the uninfected cohort but not in the HIV cohort. CD4 count <200 × 10(6) cells/L and anticoagulant use were predictive of ICH. Conclusions: HIV infection conferred an increased adjusted hazard of ICH, which was more pronounced in young patients and in women.
    No preview · Article · Oct 2014 · Neurology
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    ABSTRACT: Background: The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines are being applied to HIV-infected patients but have not been validated in this at-risk population, which is known to have a high prevalence of subclinical high-risk morphology (HRM) coronary atherosclerotic plaque. Objective: To compare recommendations for statins among HIV-infected subjects with/without HRM coronary plaque according to 2013 ACC/AHA versus 2004 Adult Treatment Panel III guidelines. Methods/design: Data from 108 HIV-infected subjects without known cardiovascular disease (CVD) or lipid-lowering treatment who underwent contrast-enhanced computed tomography angiography were analyzed. Recommendations for statin therapy according to 2013 versus 2004 guidelines were assessed among those with/without HRM coronary plaque. Results: Among all subjects, 10-year atherosclerotic cardiovascular disease (ASCVD) risk score was 3.3% (1.6, 6.6), yet 36% of subjects had HRM coronary plaque. Among those with HRM coronary plaque, statins would be recommended for 26% by 2013 guidelines versus 10% by 2004 guidelines (P=0.04). Conversely, among those without HRM coronary plaque, statins would be recommended for 19% by 2013 guidelines versus 7% by 2004 guidelines (P=0.005). In multivariate modeling, while 10-year ASCVD risk score related to HRM coronary plaque burden (P=0.02), so too did other factors not incorporated into 2013 guidelines. Conclusion: The 2013 ACC/AHA cholesterol guidelines recommend statin therapy for a higher percentage of subjects with and without HRM coronary plaque relative to 2004 guidelines. However, even by 2013 guidelines, statin therapy would not be recommended for the majority (74%) of HIV-infected subjects with subclinical HRM coronary plaque. Outcome studies are needed to determine the utility of new statin recommendations and the contribution of HRM coronary plaque to CVD events among HIVinfected subjects.
    No preview · Article · Sep 2014 · AIDS (London, England)
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    ABSTRACT: Telomere length (TL) and immune activation markers were measured in a cohort of HIV-infected (n=102) and age-matched non-HIV-infected (n=41) men. TL was significantly shorter in HIV-infected compared to non-HIV-infected subjects (P = 0.04). Univariate analysis revealed a strong inverse relationship of TL to sCD163, and thus, monocyte/macrophage activation, among the HIV group (ρ = -0.30, P = 0.003). In multivariate modeling among the whole group, HIV positive serostatus (P = 0.06) and sCD163 (P = 0.05) were independent predictors of TL controlling for age and smoking status. Our data demonstrate that increased immune activation relates to shorter TL in HIV.
    No preview · Article · Sep 2014 · JAIDS Journal of Acquired Immune Deficiency Syndromes
  • Steven K Grinspoon
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    ABSTRACT: A new paradigm for atherogenesis in HIV infection is emerging, in which viral replication and microbial translocation result in ongoing T-cell and monocyte activation, with persistent inflammation leading to the development of atypical, high-risk morphology plaques. These plaques, characterized by low attenuation and positive remodeling, can be found even among HIV-infected patients who are at low risk for cardiovascular disease based on traditional risk factors. Prevention of cardiovascular events in HIV infection requires modulation of traditional risk factors and is also likely to require effective antiinflammatory treatment strategies. Statins, which are traditionally used to treat dyslipidemia, have also been shown to exert antiinflammatory effects associated with clinical benefit and may be useful to treat and prevent cardiovascular disease in HIV-infected patients. However, large-scale studies of statins in the context of HIV infection must be conducted. This article summarizes a presentation by Steven K. Grinspoon, MD, at the IAS-USA continuing education program held in Chicago, Illinois, in May 2014.
    No preview · Article · Sep 2014 · Topics in antiviral medicine

Publication Stats

14k Citations
1,985.43 Total Impact Points

Institutions

  • 2003-2015
    • Harvard University
      Cambridge, Massachusetts, United States
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, California, United States
  • 1994-2015
    • Massachusetts General Hospital
      • • Neuroendocrine Unit
      • • Endocrine Unit
      Boston, Massachusetts, United States
  • 1970-2014
    • Harvard Medical School
      • • Department of Radiology
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2005-2011
    • Mass General Hospital
      Boston, Massachusetts, United States
  • 2007
    • McGill University Health Centre
      Montréal, Quebec, Canada
  • 2004
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States
  • 2002-2003
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
  • 1992-1994
    • Columbia University
      • Department of Medicine
      New York, New York, United States