Background: Malnutrition has been strongly associated with morbidity and mortality in hemodialysi... more Background: Malnutrition has been strongly associated with morbidity and mortality in hemodialysis patients. In the other hand, dialysis allows a nutritional improvement in patients with more than 12 months in dialysis. Aim: To study the prevalence of malnutrition among patients in hemodialysis. Patients and methods: We measured clinical, anthropometric and biochemical parameters of nutritional status in chronic hemodialysed patients. Results were related to individual time in dialysis. Patients with more and less than 12 months in dialysis were compared. Results: Twenty nine patients (18 male) aged 14 to 65 years old, were studied. Mean caloric intake was 23,8 Cal/Kg and protein intake was 0,7 g/Kg. Mean body mass index was 21.7±3.7 kg/m2 Thirty eight percent of patients had a body mass index of less than 20 kg/m2. Mean serum albumin was 4.1±0.7 g/L; mean prealbumin was 33.5±7.9 mg% and creatinine was 9.6±2.8 mg%. Serum cholesterol was 182 mg% and triacylglycerol 129 mg%. PCR was 42.2±18.8 and Kt/V was 1.45±0.3. We did not find a correlation between nutritional markers and time in dialysis or a difference in nutritional parameters between patients with less or more than 12 months in dialysis. Conclusions: These patients in chronic dialysis have a high prevalence of caloric malnutrition, which may be due to a poor caloric intake. Protein malnutrition parameters were normal in most patients. The absence of abnormal lipid levels, common in chronic renal failure, is noticeable. (Rev Med Chile 2001; 129: 495-502).
Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in L... more Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: an individual-level pooled analysis of 31 cohort studies Cohorts Consortium of Latin America and the Caribbean (CC-LAC) * , 1
Background: Ultra-processed foods have been rapidly displacing traditional dietary patterns based... more Background: Ultra-processed foods have been rapidly displacing traditional dietary patterns based on unprocessed and minimally processed foods. We assessed the time trend of food consumption based on the degree and purpose of food processing in United Kingdom from 2008 to 2016. Methods: Cross-sectional data from the National Diet and Nutrition Survey were analysed. Food items collected using a 4-day food diary were classified according to the NOVA system. Linear regression models were used to estimate linear trend of food consumption across years, adjusted for sex, social class occupation, age and region. Results: From the 2008 to 2016, the dietary contribution of processed culinary ingredients increased from 4.1% to 4.8% (p for trend<0.001), while the contribution of processed foods decreased from 9.5% to 8.4% (p for trend=0.001), respectively. The contribution of unprocessed or minimally processed foods (from 30.4% in 2008 to 30.2% in 2016; p for trend=0.462) and ultra-processed foods (from 56.0% to 56.6%, respectively; p for trend=0.194) across survey years has not appreciably changed. Regarding the subgroups, butter and plain oil (Processed culinary ingredients) increased over time, while beer, food preserved and bread (processed food) decreased. Among ultra-processed foods, pre-prepared meals, biscuits and industrial desserts increased, while reconstituted meat and margarine decreased. Among unprocessed or minimally processed foods, poultry, cereals, eggs and legumes increased, while roots, red meat and fresh fruit juice decreased. Conclusions: We observed substantial changes in the consumption of processed food and processed culinary ingredients over time. The consumption of ultra-processed food remained unchanged over time, and still account for more than half of total calorie intake in UK. Despite this, substantial changes in some subgroups including ultra-processed, were observed for the four NOVA groups. Funding: CAPES and FAPESP 2016/14302-7. Key messages: The consumption of ultra-processed food remained unchanged over time, and still account for more than half of total calorie intake in UK. Actions to mitigate high consumption ultra-processed foods are necessary given that these foods have been strongly associated with obesity and diet-related chronic diseases.
Association of Abo blood groups with gestational diabetes mellitus Background: ABO and Rhesus blo... more Association of Abo blood groups with gestational diabetes mellitus Background: ABO and Rhesus blood systems are associated with type 2 Diabetes Mellitus (DM2). Gestational Diabetes (GDM) is a model to study DM. Aim: To study the association between GDM and ABO and Rhesus groups. Material and Methods: A retrospective cohort study was performed in 1,078 women who gave birth to a singleton in Talca Regional Hospital, Chile, during 2008. We analyzed personal, obstetric, medical data and ABO and Rh blood groups. Results: GDM was diagnosed in 6.6% of women. Age and body mass index were significantly associated with GDM. There were no differences in Rh blood groups (p = 0.604), while ABO groups were different between GDM and controls. B antigen was present in 3% of GDM women and in 10.8% of controls (p = 0.037), with an odds ratio of 0.25 after adjusting for other associated risk factors (p = 0.06). Conclusions: ABO group is suggested as a possible protector marker for GDM.
Incidence of gestational diabetes and relationship to obesity in Chilean pregnant women Backgroun... more Incidence of gestational diabetes and relationship to obesity in Chilean pregnant women Background: Gestational diabetes (GDM) is associated to a worse outcome of pregnancy. This justifies efforts for finding possible causes of GDM that would allow implementing preventive interventions. Aim: To study incidence of GDM and its relation with obesity and other traditional risk factors. Material and methods: A retrospective study was performed in 234 women who had delivered a singleton during the last 12 months, attended in an outpatient clinic in Santiago, Chile. Familiar and personal history, body mass index (BMI), obstetrical-related pathology and data about the labor and the newborn were analyzed. Results: GDM was diagnosed in 11.2% of the women. BMI before pregnancy was 26.6 ± 4.4 kg/m2 (mean ± SD) and it was 25 or over in 37.8% of women. Women who developed GDM had significantly higher BMI in the pre-pregnancy stage and in the second and third trimester of pregnancy (p <0.001). The average age was greater in the GDM group (31±0.2 yr versus 26±0.41 yr). Incidence of GDM was 14.4% among women 25 years old or older and increased to 21.4% when they had, in addition, a BMI of 25 or over. Age, BMI, and family history of diabetes were all independently correlated with the development of GDM. Elective caesarean sections were more common in GDM than in non-GDM women (p = <0.01) and complications were present in 3/23 of newborns of women with GDM and 2/199 among women without GDM (p <0.01) Conclusions: GDM and obesity are highly prevalent in Chilean pregnant women. BMI, first degree relative with DM and age are independent risk factors for the development of GDM (Rev Méd Chile 2004; 132: 931-8).
Background Antimicrobial resistance is a global threat, heavily impacting low- and middle-income ... more Background Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. Methods From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. Results A total of 775 hospitalized adults and 357 community ...
Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether a... more Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. R...
Circulation: Cardiovascular Quality and Outcomes, 2019
Background: In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Sy... more Background: In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coronary syndrome in 18 924 patients. Alirocumab reduced first occurrence of the primary composite end point—coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or hospitalization for unstable angina—as well as total nonfatal cardiovascular events and all-cause deaths. The present analysis determined whether alirocumab reduced total (first and subsequent) hospitalizations and death and increased days alive and out of hospital (DAOH) and percent DAOH in ODYSSEY OUTCOMES. Methods and Results: In prespecified analyses, hazard functions for total hospitalizations and death were jointly estimated by a semiparametric model, while in post hoc analyses, DAOH and percent DAOH were compared between tre...
Journal of the American College of Cardiology, 2019
BACKGROUND Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosi... more BACKGROUND Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined. OBJECTIVES This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy. METHODS Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. RESULTS Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: À2.4% to 6.2%), and 13.0% (95% CI: À2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: À0.1% to 1.0%), 1.3% (95% CI: À1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%). CONCLUSIONS In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During
Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering the... more Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non−high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. Methods: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were ran...
OBJECTIVE Observational data associate greater prevalence of type 2 diabetes (T2D) with lower lip... more OBJECTIVE Observational data associate greater prevalence of type 2 diabetes (T2D) with lower lipoprotein(a) levels. Whether pharmacologic lowering of lipoprotein(a) influences incident T2D is unknown. We determined the relationship of lipoprotein(a) concentration to incident T2D and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS The ODYSSEY OUTCOMES trial compared alirocumab with placebo in patients with acute coronary syndrome (ACS). Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS Among 13,480 patients without diabetes at baseline, 1324 developed T2D over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio (HR) 1.04 (95% CI 1.02-1.06, P<0.001) for incident T2D. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on...
Journal of the American College of Cardiology, 2021
BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for... more BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains $70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were $70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (P interaction ¼ 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or #13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with P interaction ¼ 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an
Background: Malnutrition has been strongly associated with morbidity and mortality in hemodialysi... more Background: Malnutrition has been strongly associated with morbidity and mortality in hemodialysis patients. In the other hand, dialysis allows a nutritional improvement in patients with more than 12 months in dialysis. Aim: To study the prevalence of malnutrition among patients in hemodialysis. Patients and methods: We measured clinical, anthropometric and biochemical parameters of nutritional status in chronic hemodialysed patients. Results were related to individual time in dialysis. Patients with more and less than 12 months in dialysis were compared. Results: Twenty nine patients (18 male) aged 14 to 65 years old, were studied. Mean caloric intake was 23,8 Cal/Kg and protein intake was 0,7 g/Kg. Mean body mass index was 21.7±3.7 kg/m2 Thirty eight percent of patients had a body mass index of less than 20 kg/m2. Mean serum albumin was 4.1±0.7 g/L; mean prealbumin was 33.5±7.9 mg% and creatinine was 9.6±2.8 mg%. Serum cholesterol was 182 mg% and triacylglycerol 129 mg%. PCR was 42.2±18.8 and Kt/V was 1.45±0.3. We did not find a correlation between nutritional markers and time in dialysis or a difference in nutritional parameters between patients with less or more than 12 months in dialysis. Conclusions: These patients in chronic dialysis have a high prevalence of caloric malnutrition, which may be due to a poor caloric intake. Protein malnutrition parameters were normal in most patients. The absence of abnormal lipid levels, common in chronic renal failure, is noticeable. (Rev Med Chile 2001; 129: 495-502).
Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in L... more Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: an individual-level pooled analysis of 31 cohort studies Cohorts Consortium of Latin America and the Caribbean (CC-LAC) * , 1
Background: Ultra-processed foods have been rapidly displacing traditional dietary patterns based... more Background: Ultra-processed foods have been rapidly displacing traditional dietary patterns based on unprocessed and minimally processed foods. We assessed the time trend of food consumption based on the degree and purpose of food processing in United Kingdom from 2008 to 2016. Methods: Cross-sectional data from the National Diet and Nutrition Survey were analysed. Food items collected using a 4-day food diary were classified according to the NOVA system. Linear regression models were used to estimate linear trend of food consumption across years, adjusted for sex, social class occupation, age and region. Results: From the 2008 to 2016, the dietary contribution of processed culinary ingredients increased from 4.1% to 4.8% (p for trend<0.001), while the contribution of processed foods decreased from 9.5% to 8.4% (p for trend=0.001), respectively. The contribution of unprocessed or minimally processed foods (from 30.4% in 2008 to 30.2% in 2016; p for trend=0.462) and ultra-processed foods (from 56.0% to 56.6%, respectively; p for trend=0.194) across survey years has not appreciably changed. Regarding the subgroups, butter and plain oil (Processed culinary ingredients) increased over time, while beer, food preserved and bread (processed food) decreased. Among ultra-processed foods, pre-prepared meals, biscuits and industrial desserts increased, while reconstituted meat and margarine decreased. Among unprocessed or minimally processed foods, poultry, cereals, eggs and legumes increased, while roots, red meat and fresh fruit juice decreased. Conclusions: We observed substantial changes in the consumption of processed food and processed culinary ingredients over time. The consumption of ultra-processed food remained unchanged over time, and still account for more than half of total calorie intake in UK. Despite this, substantial changes in some subgroups including ultra-processed, were observed for the four NOVA groups. Funding: CAPES and FAPESP 2016/14302-7. Key messages: The consumption of ultra-processed food remained unchanged over time, and still account for more than half of total calorie intake in UK. Actions to mitigate high consumption ultra-processed foods are necessary given that these foods have been strongly associated with obesity and diet-related chronic diseases.
Association of Abo blood groups with gestational diabetes mellitus Background: ABO and Rhesus blo... more Association of Abo blood groups with gestational diabetes mellitus Background: ABO and Rhesus blood systems are associated with type 2 Diabetes Mellitus (DM2). Gestational Diabetes (GDM) is a model to study DM. Aim: To study the association between GDM and ABO and Rhesus groups. Material and Methods: A retrospective cohort study was performed in 1,078 women who gave birth to a singleton in Talca Regional Hospital, Chile, during 2008. We analyzed personal, obstetric, medical data and ABO and Rh blood groups. Results: GDM was diagnosed in 6.6% of women. Age and body mass index were significantly associated with GDM. There were no differences in Rh blood groups (p = 0.604), while ABO groups were different between GDM and controls. B antigen was present in 3% of GDM women and in 10.8% of controls (p = 0.037), with an odds ratio of 0.25 after adjusting for other associated risk factors (p = 0.06). Conclusions: ABO group is suggested as a possible protector marker for GDM.
Incidence of gestational diabetes and relationship to obesity in Chilean pregnant women Backgroun... more Incidence of gestational diabetes and relationship to obesity in Chilean pregnant women Background: Gestational diabetes (GDM) is associated to a worse outcome of pregnancy. This justifies efforts for finding possible causes of GDM that would allow implementing preventive interventions. Aim: To study incidence of GDM and its relation with obesity and other traditional risk factors. Material and methods: A retrospective study was performed in 234 women who had delivered a singleton during the last 12 months, attended in an outpatient clinic in Santiago, Chile. Familiar and personal history, body mass index (BMI), obstetrical-related pathology and data about the labor and the newborn were analyzed. Results: GDM was diagnosed in 11.2% of the women. BMI before pregnancy was 26.6 ± 4.4 kg/m2 (mean ± SD) and it was 25 or over in 37.8% of women. Women who developed GDM had significantly higher BMI in the pre-pregnancy stage and in the second and third trimester of pregnancy (p <0.001). The average age was greater in the GDM group (31±0.2 yr versus 26±0.41 yr). Incidence of GDM was 14.4% among women 25 years old or older and increased to 21.4% when they had, in addition, a BMI of 25 or over. Age, BMI, and family history of diabetes were all independently correlated with the development of GDM. Elective caesarean sections were more common in GDM than in non-GDM women (p = <0.01) and complications were present in 3/23 of newborns of women with GDM and 2/199 among women without GDM (p <0.01) Conclusions: GDM and obesity are highly prevalent in Chilean pregnant women. BMI, first degree relative with DM and age are independent risk factors for the development of GDM (Rev Méd Chile 2004; 132: 931-8).
Background Antimicrobial resistance is a global threat, heavily impacting low- and middle-income ... more Background Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. Methods From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. Results A total of 775 hospitalized adults and 357 community ...
Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether a... more Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. R...
Circulation: Cardiovascular Quality and Outcomes, 2019
Background: In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Sy... more Background: In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coronary syndrome in 18 924 patients. Alirocumab reduced first occurrence of the primary composite end point—coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or hospitalization for unstable angina—as well as total nonfatal cardiovascular events and all-cause deaths. The present analysis determined whether alirocumab reduced total (first and subsequent) hospitalizations and death and increased days alive and out of hospital (DAOH) and percent DAOH in ODYSSEY OUTCOMES. Methods and Results: In prespecified analyses, hazard functions for total hospitalizations and death were jointly estimated by a semiparametric model, while in post hoc analyses, DAOH and percent DAOH were compared between tre...
Journal of the American College of Cardiology, 2019
BACKGROUND Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosi... more BACKGROUND Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined. OBJECTIVES This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy. METHODS Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. RESULTS Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: À2.4% to 6.2%), and 13.0% (95% CI: À2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: À0.1% to 1.0%), 1.3% (95% CI: À1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%). CONCLUSIONS In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During
Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering the... more Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non−high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. Methods: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were ran...
OBJECTIVE Observational data associate greater prevalence of type 2 diabetes (T2D) with lower lip... more OBJECTIVE Observational data associate greater prevalence of type 2 diabetes (T2D) with lower lipoprotein(a) levels. Whether pharmacologic lowering of lipoprotein(a) influences incident T2D is unknown. We determined the relationship of lipoprotein(a) concentration to incident T2D and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS The ODYSSEY OUTCOMES trial compared alirocumab with placebo in patients with acute coronary syndrome (ACS). Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS Among 13,480 patients without diabetes at baseline, 1324 developed T2D over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio (HR) 1.04 (95% CI 1.02-1.06, P<0.001) for incident T2D. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on...
Journal of the American College of Cardiology, 2021
BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for... more BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains $70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were $70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (P interaction ¼ 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or #13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with P interaction ¼ 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an
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Papers by Laura Huidobro