David Della-morte - Academia.edu (original) (raw)
Papers by David Della-morte
Nutrients, 2019
Atherosclerosis is an inflammatory chronic disease affecting arterial vessels and leading to vasc... more Atherosclerosis is an inflammatory chronic disease affecting arterial vessels and leading to vascular diseases, such as stroke and myocardial infarction. The relationship between atherosclerosis and risk of neurodegeneration has been established, in particular with vascular cognitive impairment and dementia (VCID). Systemic atherosclerosis increases the risk of VCID by inducing cerebral infarction, or through systemic or local inflammatory factors that underlie both atherosclerosis and cognition. Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are involved in inflammatory processes, but with opposite roles. Specifically, omega-3 PUFAs exert anti-inflammatory properties by competing with omega-6 PUFAs and displacing arachidonic acid in membrane phospholipids, decreasing the production of pro-inflammatory eicosanoids. Experimental studies and some clinical trials have demonstrated that omega-3 PUFA supplementation may reduce the risk of different phenotypes of atherosclerosis ...
Ethnicity & Disease, 2017
Sickle cell anemia (SCA) is a common hematological disorder among individuals of African descent... more Sickle cell anemia (SCA) is a common hematological disorder among individuals of African descent in the United States; the disorder results in the production of abnormal hemoglobin. It is caused by homozygosity for a genetic mutation in HBB; rs334. While the presence of a single mutation (sickle cell trait, SCT) has long been considered a benign trait, recent research suggests that SCT is associated with renal dysfunction, including a decrease in estimated glomerular filtration rate (eGFR) and increased risk of chronic kidney disease (CKD) in African Americans. It is currently unknown whether similar associations are observed in Hispanics. Therefore, our study aimed to determine if SCT is associated with mean eGFR and CKD in a sample of 340 Dominican Hispanics from the Northern Manhattan Study. Using regression analyses, we tested rs334 for association with eGFR and CKD, adjusting for age and sex. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equat...
Neurology, Jan 26, 2017
Since arterial stiffness is a functional measure of arterial compliance and may be an important m... more Since arterial stiffness is a functional measure of arterial compliance and may be an important marker of cerebrovascular disease, we examined the association of carotid artery stiffness with white matter hyperintensity volume (WMHV) in a cross-sectional study of 1,166 stroke-free participants. Carotid beta stiffness index (STIFF) was assessed by M-mode ultrasound of the common carotid artery and calculated as the ratio of natural log of the difference between systolic and diastolic blood pressure over STRAIN, a ratio of the difference between carotid systolic and diastolic diameter (DD) divided by DD. WMHV was measured by fluid-attenuated inversion recovery MRI. The associations of STIFF, DD, and STRAIN with WMHV were examined using linear regression after adjusting for sociodemographic, lifestyle, and vascular risk factors. In a fully adjusted model, larger carotid DD was significantly associated with greater log-WMHV (β = 0.09, p = 0.001). STIFF and STRAIN were not significantly ...
Stroke; a journal of cerebral circulation, Jun 1, 2016
Recent drug trials have challenged the high-density lipoprotein-cholesterol (HDL-C) antiatheroscl... more Recent drug trials have challenged the high-density lipoprotein-cholesterol (HDL-C) antiatherosclerotic hypothesis, suggesting that total level of HDL-C may not be the best target for intervention. HDL-C subfractions may be better markers of vascular risk than total levels of HDL-C. The objective of this cross-sectional study was to investigate the relationship between HDL2-C and HDL3-C fractions and carotid intima-media thickness (cIMT) in the population-based Northern Manhattan Study. We evaluated 988 stroke-free participants (mean age, 66±8 years; 60% women; 66% Hispanic, and 34% non-Hispanic) with available data on HDL-C subfractions using precipitation method and cIMT assessed by a high-resolution carotid ultrasound. The associations between HDL-C subfractions and cIMT were analyzed by multiple linear regression models. The mean HDL2-C was 14±8 mg/dL, HDL3-C 32±8 mg/dL, and the mean total HDL-C was 46±14 mg/dL. The mean cIMT was 0.90±0.08 mm. After controlling for demographics ...
Hypertension, 2016
In 2014, the Eighth Joint National Committee revised the target maximum systolic blood pressure (... more In 2014, the Eighth Joint National Committee revised the target maximum systolic blood pressure (SBP) from 140 to 150 mm Hg in patients aged ≥60 years without diabetes mellitus or chronic kidney disease. The evidence from cohort studies supporting this change was sparse, particularly among US minority populations. In the Northern Manhattan Study, 1750 participants aged ≥60 years and free of stroke, diabetes mellitus, and chronic kidney disease had SBP measured at baseline and were annually followed up for incident stroke. Mean age at baseline was 72±8 years, 63% were women, 48% Hispanic, 25% non-Hispanic white, and 25% non-Hispanic black. Among all participants, 40% were on antihypertensive medications; 43% had SBP <140 mm Hg, 20% had 140 to 149 mm Hg, and 37% had ≥150 mm Hg. Over a median follow-up of 13 years, 182 participants developed stroke. The crude stroke incidence was greater among individuals with SBP≥150 mm Hg (10.8 per 1000 person-years) and SBP 140 to 149 (12.3) than...
Atherosclerosis, Jan 16, 2015
There is an established sex-difference in carotid artery intima-media thickness (cIMT), a recogni... more There is an established sex-difference in carotid artery intima-media thickness (cIMT), a recognized marker of subclinical atherosclerosis. However, the genetic underpinnings of sex-differences in gene-IMT associations are largely unknown. With a multistage design using 731,037 single nucleotide polymorphisms (SNP), a genome wide interaction study was performed in a discovery sample of 931 unrelated Hispanics, followed by replication in 153 non-Hispanic whites and 257 non-Hispanic blacks. Assuming an additive genetic model, we tested for sex-SNP interactions on cIMT using regression analysis. We did not identify any genome-wide significant SNPs but identified 14 loci with suggestive significance. Specifically, SNP-by-sex interaction was found for rs7616559 within LEKR1 gene (P = 3.5E-06 in Hispanic discovery sample, P = 0.018 in White, and P = 1.3E-06 in combined analysis) and for rs2081015 located within GALNT10 gene (P = 4.5E-06 in Hispanic discovery sample, P = 0.042 in Blacks, a...
Journal of the neurological sciences, Jan 15, 2014
Smoking greatly increases the risk of atherosclerotic plaque and the effect may vary from individ... more Smoking greatly increases the risk of atherosclerotic plaque and the effect may vary from individual to individual. A genome-wide scan was performed for smoking×single nucleotide polymorphism (SNP) interactions on carotid plaque burden (CPB) to identify the potential genetic moderators in Hispanics. Carotid B-mode ultrasonography and genotyping by the Affymetrix 6.0 chip were performed in a discovery sample of 665 Caribbean Hispanics, followed by replication analyses in 264 Caribbean Hispanics. CPB was expressed as the sum of plaque areas over the segments in common and internal carotid arteries and bifurcation. Smoking was classified as 0, <20, and ≥20 cigarette pack-years. Assuming an additive genetic model, regression analysis was conducted to test for smoking×SNP interaction on the cube root transformed CPB while controlling for age, sex, and the top 3 principal components of ancestry. Two SNPs showed a significant interaction with smoking on CPB with the similar effects in b...
Atherosclerosis, 2014
Objective-The objective of this cross-sectional analysis was to investigate the relation between ... more Objective-The objective of this cross-sectional analysis was to investigate the relation between two major high-density lipoprotein cholesterol (HDL-C) subfractions (HDL2-C and HDL3-C) and carotid plaque in a population based cohort.
Translational Research, 2015
Sirtuins (SIRTs) are a family of nicotinamide adenine dinucleotide (NAD +)-dependent deacetylases... more Sirtuins (SIRTs) are a family of nicotinamide adenine dinucleotide (NAD +)-dependent deacetylases, 1 and mitochondrial Uncoupling Proteins (UCPs) are a family of inner mitochondrial membrane proteins capable of driving the ATP-synthase pathway via regulation of the proton electrochemical gradient 2. SIRTs and UCPs have been implicated in slowing vascular aging by reducing ROS. 3 Previously we demonstrated a significant association between single nucleotide polymorphisms (SNPs) in SIRT/UCP and risk for carotid plaque (CP), number of plaques, 4 and carotid intima media thickness (cIMT) 5 as well as risk modification of these associations by vascular risk factors (RFs). Carotid stiffness (STIFF) is a measure of the vessel wall's tendency to resist deformation by systolic blood pressure (BP) during the cardiac cycle, and is considered a biologically and genetically distinct phenotypes of atherosclerosis compared with CP and cIMT. 6, 7 A previous genetic study on carotid atherosclerosis conducted among 3,300 American Indian participants, reported as the genetic linkage seen for different phenotypes of atherosclerosis
Frontiers of Neurology and Neuroscience, 2012
ABSTRACT
Pharmacogenomics, 2014
The most important goal in the treatment of patients with diabetes is to prevent the risk of card... more The most important goal in the treatment of patients with diabetes is to prevent the risk of cardiovascular disease (CVD), the first cause of mortality in these subjects. Thiazolidinediones (TZDs), a class of antidiabetic drugs, act as insulin sensitizers increasing insulin-dependent glucose disposal and reducing hepatic glucose output. TZDs including pioglitazone, rosiglitazone and troglitazone, by activating PPAR-γ have shown pleiotropic effects in reducing vascular risk factors and atherosclerosis. However, troglitazone was removed from the market due to its hepatoxicity, and rosiglitazone and pioglitazone both have particular warnings due to being associated with heart diseases. Specific genetic variations in genes involved in the pathways regulated by TDZs have demonstrated to modify the variability in treatment with these drugs, especially in their side effects. Therefore, pharmacogenomics and pharmacogenetics are an important tool in further understand intersubject variabilit...
Stroke, 2010
Background and Purpose— Homocysteine levels are determined by genetic and environmental factors. ... more Background and Purpose— Homocysteine levels are determined by genetic and environmental factors. Several studies have linked high plasma levels of total homocysteine to the increased risk of cardiovascular disease, stroke, and many other conditions. However, the exact mechanism of documented and novel total homocysteine quantitative trait loci to that risk is unknown. Methods— We have performed linkage analysis in 100 high-risk Dominican families with 1362 members. Probands were selected from the population-based Northern Manhattan Study. A set of 405 microsatellite markers was used to screen the whole genome. Variance components analysis was used to detect evidence for linkage after adjusting for stroke risk factors. Ordered-subset analysis based on Dominican Republic enrollment was conducted. Results— Total homocysteine levels had a heritability of 0.44 ( P <0.0001). The most significant evidence for linkage was found at chromosome 17q24 (maximum logarithm of odds [MLOD]=2.66, ...
Stroke, 2011
Background and Purpose— Few studies have examined the early effects of statins on carotid artery ... more Background and Purpose— Few studies have examined the early effects of statins on carotid artery elasticity, a potential surrogate marker of cardiovascular risk. This study examined the short-term effects of atorvastatin 80 mg daily on carotid elasticity measured by high-resolution B-mode ultrasound. Methods— The study included 40 stroke-free and statin-naive subjects older than age 45 (mean age, 70±7 years; 55% men; 64% Caribbean-Hispanic). Outcome measures included carotid stiffness indices at 14 and 30 days after initiation of treatment. The systolic and diastolic diameters of the right common carotid artery were averaged from multiple B-mode imaging frames. Absolute and relative changes of strain [(systolic diameter−diastolic diameter)/diastolic diameter], stiffness (β) [ln (systolic/diastolic blood pressure)/strain], and distensibility (1/β adjusted for wall thickness) from baseline were compared by the repeated measures t test and were considered significant at α=0.05. Results...
PLoS ONE, 2011
Objective: Sirtuins (SIRTs) and mitochondrial uncoupling proteins (UCPs) have been implicated in ... more Objective: Sirtuins (SIRTs) and mitochondrial uncoupling proteins (UCPs) have been implicated in cardiovascular diseases through the control of reactive oxygen species production. This study sought to investigate the association between genetic variants in the SIRT and UCP genes and carotid plaque. Methods: In a group of 1018 stroke-free subjects from the Northern Manhattan Study with high-definition carotid ultrasonography and genotyping, we investigated the associations of 85 single nucleotide polymorphisms (SNPs) in the 11 SIRT and UCP genes with the presence and number of carotid plaques, and evaluated interactions of SNPs with sex, smoking, diabetes and hypertension as well as interactions between SNPs significantly associated with carotid plaque. Results: Overall, 60% of subjects had carotid plaques. After adjustment for demographic and vascular risk factors, T-carriers of the SIRT6 SNP rs107251 had an increased risk for carotid plaque (odds ratio, OR = 1.71, 95% CI = 1.23-2.37, Bonferronicorrected p = 0.03) and for a number of plaques (rate ratio, RR = 1.31, 1.18-1.45, Bonferroni-corrected p = 1.4610 25), whereas T-carriers of the UCP5 SNP rs5977238 had an decreased risk for carotid plaque (OR = 0.49, 95% CI = 0.32-0.74, Bonferroni-corrected p = 0.02) and plaque number (RR = 0.64, 95% CI = 0.52-0.78, Bonferroni-corrected p = 4.9610 24). Some interactions with a nominal p#0.01 were found between sex and SNPs in the UCP1 and UCP3 gene; between smoking, diabetes, hypertension and SNPs in UCP5 and SIRT5; and between SNPs in the UCP5 gene and the UCP1, SIRT1, SIRT3, SIRT5, and SIRT6 genes in association with plaque phenotypes. Conclusion: We observed significant associations between genetic variants in the SIRT6 and UCP5 genes and atherosclerotic plaque. We also found potential effect modifications by sex, smoking and vascular risk factors of the SIRT/UCP genes in the associations with atherosclerotic plaque. Further studies are needed to validate our observations.
Neurological Research, 2011
Soft, lipid-containing carotid plaques, which appear echolucent on ultrasound imaging, have been ... more Soft, lipid-containing carotid plaques, which appear echolucent on ultrasound imaging, have been associated with increased risk of ischemic stroke. We sought to investigate the effect of short-term treatment with atorvastatin on the change of carotid plaque echodensity. We treated 40 stroke-free and statin-naive subjects with 80 mg atorvastatin daily for 30 days. Computer assisted gray-scale densitometry (GSD) index was calculated at baseline and 30 days after treatment from the normalized plaque images. A multiple logistic regression was used to assess the effect modification of low-density lipoprotein (LDL) cholesterol on plaque stabilization after adjusting for age, sex, and smoking. The average number of carotid plaques at baseline was 2 (range: 0-5; 27 subjects with carotid plaque) and did not change 30 days following atorvastatin treatment. The mean GSD index significantly increased from 73±16 (range: 1-125) at baseline to 89±15 (range: 1-137) at 30 days after treatment (P<0.05). The adjusted odds ratio for the positive GSD plaque index change (vs. no change or decreased gray-scale median (GSM) index) was 1.71 (95% confidence interval: 1.1-7.6, P<0.01). In conclusion, we observed decreased echolucency (increased echodensity) of carotid artery plaques after short-term treatment with atorvastatin.
Journal of Vascular Surgery, 2013
Conclusion: Surgical malpractice claims are demonstrating increasing payment amounts, with patien... more Conclusion: Surgical malpractice claims are demonstrating increasing payment amounts, with patient outcomes the strongest predictor of payment size. Summary: The effect of medical liability on the health care system is more than the sum of payments to plaintiffs. Other costs include practicing defensive medicine, administrative expenses, and attorney fees, among others. It has been estimated that all of these costs combined to account for 2.4% of health care expenditures (w$55.6 billion dollars annually; Mello MN et al, Health AFF (Millwood) 2010;29:1569-77). Congress passed the Healthcare Quality Improvement Act in 1988 in an attempt to identify those who provided incompetent care. The National Practitioner Data Bank (NPDB) was created by the U.S. Department of Health and Human Services and has a mandatory reporting system of medical malpractice payments. The NPDB contains data reported by malpractice carriers, hospitals, and professional societies as well as state licensing boards since 1990. Since the creation of the NPDB, there has not been an analysis of surgical malpractice claims using this database. The authors of this study sought to discover patterns and predictors of surgical malpractice payments and, specifically, to evaluate predictors of large payments. This was a retrospective analysis of surgery-related malpractice payments using the NPBD from 1990 to 2006 with payments adjusted to 2006 dollars. Predictors of payment size and payments considered large (>$1 million) were evaluated. Statutory law in the states demonstrating significant predictive value was also analyzed. There were 58,518 surgical malpractice claims that met inclusion criteria. Patients were mostly female (62%) and inpatients (63%). Mean age was 42 years. During the study period, the number of payments decreased but payment sums increased. Median payments were 132,915(95thpercentile,132,915 (95th percentile, 132,915(95thpercentile,983,263). The most frequently cited reason for the claim was improper performance (42%). Payment size and likelihood of a large payment were both primarily predicated by patient outcomes. In addition, children aged <10 years were 70% more likely to receive a large payment (P ¼ .005), and patients aged >70 years were 80% less likely to receive a large payment (P < .005). There were large variations among states for payment size and likelihood of a large payment. Comment: Of the >750,000 entries in the NPDB, 1% are surgeryrelated malpractice claims. Surgeons have the highest perceived threat of malpractice suits, and 90% of surgeons aged $55 years have been reported to have been sued for medical malpractice (Kane CK, American Medical Association; 2010). Variation in payment size among the states suggests that the local legal environment has a significant impact on payment size. The implication is that local efforts to improve the medical malpractice environment remain the most important possibility of achieving meaningful medical malpractice reform.
Journal of the Neurological Sciences, 2012
Objective-Genetic variation in coagulation and fibrinolysis may affect the development of subclin... more Objective-Genetic variation in coagulation and fibrinolysis may affect the development of subclinical atherosclerosis modifying the risk of stroke and cardiovascular disease. However, data on the relationship between subclinical atherosclerosis and genes involved in the coagulation system are sparse. The objective of this study is to examine the association between single nucleotide polymorphisms (SNPs) in coagulation system genes and subclinical carotid plaque phenotypes. Methods-From the Genetic Determinants of Subclinical Carotid Disease study, 287 Dominicans were examined for carotid plaque presence, thickness, and surface irregularity by high-resolution B-mode carotid ultrasound. Logistic regression was used to test for association between 101 SNPs in 23 coagulation system genes and plaque phenotypes while controlling for age, sex, smoking, hypertension, dyslipidemia, and diabetes. Within gene haplotypes and interactions between genes were examined. A follow-up of SNPs in moderate to high (r 2 >0.25) linkage disequilibrium (LD) with those implicated in the discovery analysis (p≤0.01) was performed in an independent sample of 301 Dominicans. Results-The prevalence of carotid plaque (47% discovery; 46% follow-up) as well as the mean age (65±8 discovery; 65±9 follow-up) of the participants was similar in both datasets. Two genes (vWF and THBS1) were associated (p≤0.01) with plaque size and surface irregularity. In followup, 5 SNPs in vWF were associated (p≤0.05) with plaque size. SERPINE1 was an additional gene of interest in the haplotype and interaction analyses. Conclusions-Variation in the vWF, THBS1, and SERPINE1 gene may play an important role in the pathogenesis of atherosclerotic plaque.
Journal of the American Geriatrics Society, 2013
International Journal of Stroke, 2010
Background Arterial stiffness, an intermediate pre-clinical marker of atherosclerosis, has been a... more Background Arterial stiffness, an intermediate pre-clinical marker of atherosclerosis, has been associated with an increased risk of stroke and cardiovascular disease. The metabolic syndrome and its components are established cardiovascular disease risk factors and may also increase arterial stiffness; however, data regarding this are limited. Aim The goal of this study was to determine the association between the metabolic syndrome and carotid artery stiffness in an elderly multi-ethnic cohort. Methods Carotid artery stiffness was assessed by carotid ultrasound as part of the Northern Manhattan Study, a prospective population-based cohort of stroke-free individuals. Carotid artery stiffness was calculated as [In (systolic BP/diastolic BP)/strain], where strain was [(systolic diameter diastolic diameter)/diastolic diameter]. Metabolic syndrome was defined by the National Cholesterol Education Program: Adult Treatment Panel III criteria. LogSTIFF was analysed as the dependent variabl...
Current Vascular Pharmacology, 2013
Nutrients, 2019
Atherosclerosis is an inflammatory chronic disease affecting arterial vessels and leading to vasc... more Atherosclerosis is an inflammatory chronic disease affecting arterial vessels and leading to vascular diseases, such as stroke and myocardial infarction. The relationship between atherosclerosis and risk of neurodegeneration has been established, in particular with vascular cognitive impairment and dementia (VCID). Systemic atherosclerosis increases the risk of VCID by inducing cerebral infarction, or through systemic or local inflammatory factors that underlie both atherosclerosis and cognition. Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are involved in inflammatory processes, but with opposite roles. Specifically, omega-3 PUFAs exert anti-inflammatory properties by competing with omega-6 PUFAs and displacing arachidonic acid in membrane phospholipids, decreasing the production of pro-inflammatory eicosanoids. Experimental studies and some clinical trials have demonstrated that omega-3 PUFA supplementation may reduce the risk of different phenotypes of atherosclerosis ...
Ethnicity & Disease, 2017
Sickle cell anemia (SCA) is a common hematological disorder among individuals of African descent... more Sickle cell anemia (SCA) is a common hematological disorder among individuals of African descent in the United States; the disorder results in the production of abnormal hemoglobin. It is caused by homozygosity for a genetic mutation in HBB; rs334. While the presence of a single mutation (sickle cell trait, SCT) has long been considered a benign trait, recent research suggests that SCT is associated with renal dysfunction, including a decrease in estimated glomerular filtration rate (eGFR) and increased risk of chronic kidney disease (CKD) in African Americans. It is currently unknown whether similar associations are observed in Hispanics. Therefore, our study aimed to determine if SCT is associated with mean eGFR and CKD in a sample of 340 Dominican Hispanics from the Northern Manhattan Study. Using regression analyses, we tested rs334 for association with eGFR and CKD, adjusting for age and sex. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equat...
Neurology, Jan 26, 2017
Since arterial stiffness is a functional measure of arterial compliance and may be an important m... more Since arterial stiffness is a functional measure of arterial compliance and may be an important marker of cerebrovascular disease, we examined the association of carotid artery stiffness with white matter hyperintensity volume (WMHV) in a cross-sectional study of 1,166 stroke-free participants. Carotid beta stiffness index (STIFF) was assessed by M-mode ultrasound of the common carotid artery and calculated as the ratio of natural log of the difference between systolic and diastolic blood pressure over STRAIN, a ratio of the difference between carotid systolic and diastolic diameter (DD) divided by DD. WMHV was measured by fluid-attenuated inversion recovery MRI. The associations of STIFF, DD, and STRAIN with WMHV were examined using linear regression after adjusting for sociodemographic, lifestyle, and vascular risk factors. In a fully adjusted model, larger carotid DD was significantly associated with greater log-WMHV (β = 0.09, p = 0.001). STIFF and STRAIN were not significantly ...
Stroke; a journal of cerebral circulation, Jun 1, 2016
Recent drug trials have challenged the high-density lipoprotein-cholesterol (HDL-C) antiatheroscl... more Recent drug trials have challenged the high-density lipoprotein-cholesterol (HDL-C) antiatherosclerotic hypothesis, suggesting that total level of HDL-C may not be the best target for intervention. HDL-C subfractions may be better markers of vascular risk than total levels of HDL-C. The objective of this cross-sectional study was to investigate the relationship between HDL2-C and HDL3-C fractions and carotid intima-media thickness (cIMT) in the population-based Northern Manhattan Study. We evaluated 988 stroke-free participants (mean age, 66±8 years; 60% women; 66% Hispanic, and 34% non-Hispanic) with available data on HDL-C subfractions using precipitation method and cIMT assessed by a high-resolution carotid ultrasound. The associations between HDL-C subfractions and cIMT were analyzed by multiple linear regression models. The mean HDL2-C was 14±8 mg/dL, HDL3-C 32±8 mg/dL, and the mean total HDL-C was 46±14 mg/dL. The mean cIMT was 0.90±0.08 mm. After controlling for demographics ...
Hypertension, 2016
In 2014, the Eighth Joint National Committee revised the target maximum systolic blood pressure (... more In 2014, the Eighth Joint National Committee revised the target maximum systolic blood pressure (SBP) from 140 to 150 mm Hg in patients aged ≥60 years without diabetes mellitus or chronic kidney disease. The evidence from cohort studies supporting this change was sparse, particularly among US minority populations. In the Northern Manhattan Study, 1750 participants aged ≥60 years and free of stroke, diabetes mellitus, and chronic kidney disease had SBP measured at baseline and were annually followed up for incident stroke. Mean age at baseline was 72±8 years, 63% were women, 48% Hispanic, 25% non-Hispanic white, and 25% non-Hispanic black. Among all participants, 40% were on antihypertensive medications; 43% had SBP <140 mm Hg, 20% had 140 to 149 mm Hg, and 37% had ≥150 mm Hg. Over a median follow-up of 13 years, 182 participants developed stroke. The crude stroke incidence was greater among individuals with SBP≥150 mm Hg (10.8 per 1000 person-years) and SBP 140 to 149 (12.3) than...
Atherosclerosis, Jan 16, 2015
There is an established sex-difference in carotid artery intima-media thickness (cIMT), a recogni... more There is an established sex-difference in carotid artery intima-media thickness (cIMT), a recognized marker of subclinical atherosclerosis. However, the genetic underpinnings of sex-differences in gene-IMT associations are largely unknown. With a multistage design using 731,037 single nucleotide polymorphisms (SNP), a genome wide interaction study was performed in a discovery sample of 931 unrelated Hispanics, followed by replication in 153 non-Hispanic whites and 257 non-Hispanic blacks. Assuming an additive genetic model, we tested for sex-SNP interactions on cIMT using regression analysis. We did not identify any genome-wide significant SNPs but identified 14 loci with suggestive significance. Specifically, SNP-by-sex interaction was found for rs7616559 within LEKR1 gene (P = 3.5E-06 in Hispanic discovery sample, P = 0.018 in White, and P = 1.3E-06 in combined analysis) and for rs2081015 located within GALNT10 gene (P = 4.5E-06 in Hispanic discovery sample, P = 0.042 in Blacks, a...
Journal of the neurological sciences, Jan 15, 2014
Smoking greatly increases the risk of atherosclerotic plaque and the effect may vary from individ... more Smoking greatly increases the risk of atherosclerotic plaque and the effect may vary from individual to individual. A genome-wide scan was performed for smoking×single nucleotide polymorphism (SNP) interactions on carotid plaque burden (CPB) to identify the potential genetic moderators in Hispanics. Carotid B-mode ultrasonography and genotyping by the Affymetrix 6.0 chip were performed in a discovery sample of 665 Caribbean Hispanics, followed by replication analyses in 264 Caribbean Hispanics. CPB was expressed as the sum of plaque areas over the segments in common and internal carotid arteries and bifurcation. Smoking was classified as 0, <20, and ≥20 cigarette pack-years. Assuming an additive genetic model, regression analysis was conducted to test for smoking×SNP interaction on the cube root transformed CPB while controlling for age, sex, and the top 3 principal components of ancestry. Two SNPs showed a significant interaction with smoking on CPB with the similar effects in b...
Atherosclerosis, 2014
Objective-The objective of this cross-sectional analysis was to investigate the relation between ... more Objective-The objective of this cross-sectional analysis was to investigate the relation between two major high-density lipoprotein cholesterol (HDL-C) subfractions (HDL2-C and HDL3-C) and carotid plaque in a population based cohort.
Translational Research, 2015
Sirtuins (SIRTs) are a family of nicotinamide adenine dinucleotide (NAD +)-dependent deacetylases... more Sirtuins (SIRTs) are a family of nicotinamide adenine dinucleotide (NAD +)-dependent deacetylases, 1 and mitochondrial Uncoupling Proteins (UCPs) are a family of inner mitochondrial membrane proteins capable of driving the ATP-synthase pathway via regulation of the proton electrochemical gradient 2. SIRTs and UCPs have been implicated in slowing vascular aging by reducing ROS. 3 Previously we demonstrated a significant association between single nucleotide polymorphisms (SNPs) in SIRT/UCP and risk for carotid plaque (CP), number of plaques, 4 and carotid intima media thickness (cIMT) 5 as well as risk modification of these associations by vascular risk factors (RFs). Carotid stiffness (STIFF) is a measure of the vessel wall's tendency to resist deformation by systolic blood pressure (BP) during the cardiac cycle, and is considered a biologically and genetically distinct phenotypes of atherosclerosis compared with CP and cIMT. 6, 7 A previous genetic study on carotid atherosclerosis conducted among 3,300 American Indian participants, reported as the genetic linkage seen for different phenotypes of atherosclerosis
Frontiers of Neurology and Neuroscience, 2012
ABSTRACT
Pharmacogenomics, 2014
The most important goal in the treatment of patients with diabetes is to prevent the risk of card... more The most important goal in the treatment of patients with diabetes is to prevent the risk of cardiovascular disease (CVD), the first cause of mortality in these subjects. Thiazolidinediones (TZDs), a class of antidiabetic drugs, act as insulin sensitizers increasing insulin-dependent glucose disposal and reducing hepatic glucose output. TZDs including pioglitazone, rosiglitazone and troglitazone, by activating PPAR-γ have shown pleiotropic effects in reducing vascular risk factors and atherosclerosis. However, troglitazone was removed from the market due to its hepatoxicity, and rosiglitazone and pioglitazone both have particular warnings due to being associated with heart diseases. Specific genetic variations in genes involved in the pathways regulated by TDZs have demonstrated to modify the variability in treatment with these drugs, especially in their side effects. Therefore, pharmacogenomics and pharmacogenetics are an important tool in further understand intersubject variabilit...
Stroke, 2010
Background and Purpose— Homocysteine levels are determined by genetic and environmental factors. ... more Background and Purpose— Homocysteine levels are determined by genetic and environmental factors. Several studies have linked high plasma levels of total homocysteine to the increased risk of cardiovascular disease, stroke, and many other conditions. However, the exact mechanism of documented and novel total homocysteine quantitative trait loci to that risk is unknown. Methods— We have performed linkage analysis in 100 high-risk Dominican families with 1362 members. Probands were selected from the population-based Northern Manhattan Study. A set of 405 microsatellite markers was used to screen the whole genome. Variance components analysis was used to detect evidence for linkage after adjusting for stroke risk factors. Ordered-subset analysis based on Dominican Republic enrollment was conducted. Results— Total homocysteine levels had a heritability of 0.44 ( P <0.0001). The most significant evidence for linkage was found at chromosome 17q24 (maximum logarithm of odds [MLOD]=2.66, ...
Stroke, 2011
Background and Purpose— Few studies have examined the early effects of statins on carotid artery ... more Background and Purpose— Few studies have examined the early effects of statins on carotid artery elasticity, a potential surrogate marker of cardiovascular risk. This study examined the short-term effects of atorvastatin 80 mg daily on carotid elasticity measured by high-resolution B-mode ultrasound. Methods— The study included 40 stroke-free and statin-naive subjects older than age 45 (mean age, 70±7 years; 55% men; 64% Caribbean-Hispanic). Outcome measures included carotid stiffness indices at 14 and 30 days after initiation of treatment. The systolic and diastolic diameters of the right common carotid artery were averaged from multiple B-mode imaging frames. Absolute and relative changes of strain [(systolic diameter−diastolic diameter)/diastolic diameter], stiffness (β) [ln (systolic/diastolic blood pressure)/strain], and distensibility (1/β adjusted for wall thickness) from baseline were compared by the repeated measures t test and were considered significant at α=0.05. Results...
PLoS ONE, 2011
Objective: Sirtuins (SIRTs) and mitochondrial uncoupling proteins (UCPs) have been implicated in ... more Objective: Sirtuins (SIRTs) and mitochondrial uncoupling proteins (UCPs) have been implicated in cardiovascular diseases through the control of reactive oxygen species production. This study sought to investigate the association between genetic variants in the SIRT and UCP genes and carotid plaque. Methods: In a group of 1018 stroke-free subjects from the Northern Manhattan Study with high-definition carotid ultrasonography and genotyping, we investigated the associations of 85 single nucleotide polymorphisms (SNPs) in the 11 SIRT and UCP genes with the presence and number of carotid plaques, and evaluated interactions of SNPs with sex, smoking, diabetes and hypertension as well as interactions between SNPs significantly associated with carotid plaque. Results: Overall, 60% of subjects had carotid plaques. After adjustment for demographic and vascular risk factors, T-carriers of the SIRT6 SNP rs107251 had an increased risk for carotid plaque (odds ratio, OR = 1.71, 95% CI = 1.23-2.37, Bonferronicorrected p = 0.03) and for a number of plaques (rate ratio, RR = 1.31, 1.18-1.45, Bonferroni-corrected p = 1.4610 25), whereas T-carriers of the UCP5 SNP rs5977238 had an decreased risk for carotid plaque (OR = 0.49, 95% CI = 0.32-0.74, Bonferroni-corrected p = 0.02) and plaque number (RR = 0.64, 95% CI = 0.52-0.78, Bonferroni-corrected p = 4.9610 24). Some interactions with a nominal p#0.01 were found between sex and SNPs in the UCP1 and UCP3 gene; between smoking, diabetes, hypertension and SNPs in UCP5 and SIRT5; and between SNPs in the UCP5 gene and the UCP1, SIRT1, SIRT3, SIRT5, and SIRT6 genes in association with plaque phenotypes. Conclusion: We observed significant associations between genetic variants in the SIRT6 and UCP5 genes and atherosclerotic plaque. We also found potential effect modifications by sex, smoking and vascular risk factors of the SIRT/UCP genes in the associations with atherosclerotic plaque. Further studies are needed to validate our observations.
Neurological Research, 2011
Soft, lipid-containing carotid plaques, which appear echolucent on ultrasound imaging, have been ... more Soft, lipid-containing carotid plaques, which appear echolucent on ultrasound imaging, have been associated with increased risk of ischemic stroke. We sought to investigate the effect of short-term treatment with atorvastatin on the change of carotid plaque echodensity. We treated 40 stroke-free and statin-naive subjects with 80 mg atorvastatin daily for 30 days. Computer assisted gray-scale densitometry (GSD) index was calculated at baseline and 30 days after treatment from the normalized plaque images. A multiple logistic regression was used to assess the effect modification of low-density lipoprotein (LDL) cholesterol on plaque stabilization after adjusting for age, sex, and smoking. The average number of carotid plaques at baseline was 2 (range: 0-5; 27 subjects with carotid plaque) and did not change 30 days following atorvastatin treatment. The mean GSD index significantly increased from 73±16 (range: 1-125) at baseline to 89±15 (range: 1-137) at 30 days after treatment (P<0.05). The adjusted odds ratio for the positive GSD plaque index change (vs. no change or decreased gray-scale median (GSM) index) was 1.71 (95% confidence interval: 1.1-7.6, P<0.01). In conclusion, we observed decreased echolucency (increased echodensity) of carotid artery plaques after short-term treatment with atorvastatin.
Journal of Vascular Surgery, 2013
Conclusion: Surgical malpractice claims are demonstrating increasing payment amounts, with patien... more Conclusion: Surgical malpractice claims are demonstrating increasing payment amounts, with patient outcomes the strongest predictor of payment size. Summary: The effect of medical liability on the health care system is more than the sum of payments to plaintiffs. Other costs include practicing defensive medicine, administrative expenses, and attorney fees, among others. It has been estimated that all of these costs combined to account for 2.4% of health care expenditures (w$55.6 billion dollars annually; Mello MN et al, Health AFF (Millwood) 2010;29:1569-77). Congress passed the Healthcare Quality Improvement Act in 1988 in an attempt to identify those who provided incompetent care. The National Practitioner Data Bank (NPDB) was created by the U.S. Department of Health and Human Services and has a mandatory reporting system of medical malpractice payments. The NPDB contains data reported by malpractice carriers, hospitals, and professional societies as well as state licensing boards since 1990. Since the creation of the NPDB, there has not been an analysis of surgical malpractice claims using this database. The authors of this study sought to discover patterns and predictors of surgical malpractice payments and, specifically, to evaluate predictors of large payments. This was a retrospective analysis of surgery-related malpractice payments using the NPBD from 1990 to 2006 with payments adjusted to 2006 dollars. Predictors of payment size and payments considered large (>$1 million) were evaluated. Statutory law in the states demonstrating significant predictive value was also analyzed. There were 58,518 surgical malpractice claims that met inclusion criteria. Patients were mostly female (62%) and inpatients (63%). Mean age was 42 years. During the study period, the number of payments decreased but payment sums increased. Median payments were 132,915(95thpercentile,132,915 (95th percentile, 132,915(95thpercentile,983,263). The most frequently cited reason for the claim was improper performance (42%). Payment size and likelihood of a large payment were both primarily predicated by patient outcomes. In addition, children aged <10 years were 70% more likely to receive a large payment (P ¼ .005), and patients aged >70 years were 80% less likely to receive a large payment (P < .005). There were large variations among states for payment size and likelihood of a large payment. Comment: Of the >750,000 entries in the NPDB, 1% are surgeryrelated malpractice claims. Surgeons have the highest perceived threat of malpractice suits, and 90% of surgeons aged $55 years have been reported to have been sued for medical malpractice (Kane CK, American Medical Association; 2010). Variation in payment size among the states suggests that the local legal environment has a significant impact on payment size. The implication is that local efforts to improve the medical malpractice environment remain the most important possibility of achieving meaningful medical malpractice reform.
Journal of the Neurological Sciences, 2012
Objective-Genetic variation in coagulation and fibrinolysis may affect the development of subclin... more Objective-Genetic variation in coagulation and fibrinolysis may affect the development of subclinical atherosclerosis modifying the risk of stroke and cardiovascular disease. However, data on the relationship between subclinical atherosclerosis and genes involved in the coagulation system are sparse. The objective of this study is to examine the association between single nucleotide polymorphisms (SNPs) in coagulation system genes and subclinical carotid plaque phenotypes. Methods-From the Genetic Determinants of Subclinical Carotid Disease study, 287 Dominicans were examined for carotid plaque presence, thickness, and surface irregularity by high-resolution B-mode carotid ultrasound. Logistic regression was used to test for association between 101 SNPs in 23 coagulation system genes and plaque phenotypes while controlling for age, sex, smoking, hypertension, dyslipidemia, and diabetes. Within gene haplotypes and interactions between genes were examined. A follow-up of SNPs in moderate to high (r 2 >0.25) linkage disequilibrium (LD) with those implicated in the discovery analysis (p≤0.01) was performed in an independent sample of 301 Dominicans. Results-The prevalence of carotid plaque (47% discovery; 46% follow-up) as well as the mean age (65±8 discovery; 65±9 follow-up) of the participants was similar in both datasets. Two genes (vWF and THBS1) were associated (p≤0.01) with plaque size and surface irregularity. In followup, 5 SNPs in vWF were associated (p≤0.05) with plaque size. SERPINE1 was an additional gene of interest in the haplotype and interaction analyses. Conclusions-Variation in the vWF, THBS1, and SERPINE1 gene may play an important role in the pathogenesis of atherosclerotic plaque.
Journal of the American Geriatrics Society, 2013
International Journal of Stroke, 2010
Background Arterial stiffness, an intermediate pre-clinical marker of atherosclerosis, has been a... more Background Arterial stiffness, an intermediate pre-clinical marker of atherosclerosis, has been associated with an increased risk of stroke and cardiovascular disease. The metabolic syndrome and its components are established cardiovascular disease risk factors and may also increase arterial stiffness; however, data regarding this are limited. Aim The goal of this study was to determine the association between the metabolic syndrome and carotid artery stiffness in an elderly multi-ethnic cohort. Methods Carotid artery stiffness was assessed by carotid ultrasound as part of the Northern Manhattan Study, a prospective population-based cohort of stroke-free individuals. Carotid artery stiffness was calculated as [In (systolic BP/diastolic BP)/strain], where strain was [(systolic diameter diastolic diameter)/diastolic diameter]. Metabolic syndrome was defined by the National Cholesterol Education Program: Adult Treatment Panel III criteria. LogSTIFF was analysed as the dependent variabl...
Current Vascular Pharmacology, 2013