A Long Duration of Reflux Symptoms is the Predominant Risk Factor for Depression in Vietnamese Patients with Gastroesophageal Reflux Disease.

Purpose: Depression is more prevalent in patients with gastroesophageal reflux disease (GERD) than in controls. The disorder can worsen the quality of life of GERD patients and is also associated with poor treatment response. However, there are limited data on its prevalence and risk factors in GERD patients in Southeast Asia. We aimed to assess the prevalence and severity of depression and its associated factors in Vietnamese patients with GERD. Patients and methods: A cross-sectional study was conducted on GERD patients. GERD was defined as troublesome typical reflux symptoms at least twice a week or having endoscopic erosive reflux disease. The revised Beck's Depression Inventory (BDI-IA), which has been locally validated, was used to evaluate depression (BDI-IA < 10: none, 10-18: mild to moderate, 19-29: moderate to severe, and ≥ 30: severe depression). Multiple logistic regression analysis was used to identify independent factors associated with depression. Results: A total of 194 patients were recruited. The mean age was 44.1 ± 12.0 years, and the male-to-female ratio was 1:1.2. The depression rate was 47.9% (mild to moderate: 30.9%, moderate to severe: 16.0%, and severe: 1.0%). In multivariate analysis, sex and duration of reflux symptoms were the only two risk factors for depression. Compared to males, females were more likely to suffer from depression: odds ratio (OR) = 3.941 (95% confidence interval [CI], 1.386-11.205), p = 0.010. Compared to patients with a duration of reflux symptoms < 1 year, those with a duration of 1-10 years and > 10 years were more likely to suffer from depression with a dose‒response: OR = 3.520 (95% CI, 1.057-11.717), p = 0.040; and OR = 5.605 (1.046-30.019), p = 0.044, respectively. Conclusion: Depression was prevalent, and a long duration of reflux symptoms was its predominant risk factor in Vietnamese patients with GERD.

Mechanical regulation of talin through binding and history-dependent unfolding.

Talin is a force-sensing multidomain protein and a major player in cellular mechanotransduction. Here, we use single-molecule magnetic tweezers to investigate the mechanical response of the R8 rod domain of talin. We find that under various force cycles, the R8 domain of talin can display a memory-dependent behavior: At the same low force (<10 pN), the same protein molecule shows vastly different unfolding kinetics. This history-dependent behavior indicates the evolution of a unique force-induced native state. We measure through mechanical unfolding that talin R8 domain binds one of its ligands, DLC1, with much higher affinity than previously reported. This strong interaction can explain the antitumor response of DLC1 by regulating inside-out activation of integrins. Together, our results paint a complex picture for the mechanical unfolding of talin in the physiological range and a new mechanism of function of DLC1 to regulate inside-out activation of integrins.

Systematic review of drug-drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management.

Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%-74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3-5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%-67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.

Association between statin use, atherosclerosis, and mortality in HIV-infected adults.

BACKGROUND: While HIV infection is associated with increased cardiovascular risk, benefit from statin is not well established in HIV-infected adults. We assessed whether statins are associated with a decrease in carotid artery intima-media thickness (cIMT) progression and all-cause mortality in HIV-infected adults who are at elevated ASCVD risk and recommended for statins. METHODS: Carotid IMT was measured at baseline and follow-up in 127 HIV-infected adults who meet ACC/AHA criteria to be on statins. Inverse probability of treatment weighting (IPTW) was used to address selection bias. Multivariable models were used to control for baseline characteristics. RESULTS: 28 subjects (22%) were on statins and 99 subjects (78%) were not. Mean cIMT at baseline was 1.2 mm (SD = 0.34) in statin users and 1.1 mm (SD = 0.34) in non-users, and the multivariable adjusted difference was 0.05mm (95%CI -0.11, 0.21 p = 0.53). After 3.2 years of follow-up, average cIMT progression was similar in statin users and non-users (0.062mm/yr vs. 0.058 mm/yr) and the multivariable adjusted difference over the study period was 0.004 mm/yr (95% CI -0.018, 0.025, p = 0.74). All-cause mortality appeared higher in non-statin users compared with statin users, but the difference was not significant (adjusted HR = 0.74, 95%CI 0.17-3.29, p = 0.70). CONCLUSION: In a HIV cohort who had elevated ASCVD risk and meet ACC/AHA criteria for statins, treatment with statins was not associated with a reduction in carotid atherosclerosis progression or total mortality. Future studies are needed to further explore the impact of statins on cardiovascular risk in the HIV-infected population.

Methods and Applications of Biomolecular Surface Coatings on Individual Cells.

The complete recovery of tissues or cells damaged by an accident or illness is a major issue in medicine. With increasing medical costs and incidences of incurable diseases, this aspect is emerging as an important human health problem worldwide. However, reproducing actual cells and tissues is not easy because of the involvement of several variables. External environmental changes such as different pH levels, the presence of oxidants, and ultraviolet exposure can impair cell function or trigger cell death owing to the limitations of the cells. In addition, transplanted therapeutic cells die easily owing to inflammatory and immune responses. Efforts to overcome this problem through multilayer cell coating can provide avenues for diagnosis and basic cell biology studies owing to the following features of multilayer films: (i) high capacity available for attaching different biomolecules; (ii) natural replication of signal molecule diffusion across cells; and (iii) the possibility of cell patterning. Furthermore, light-triggered release from multilayer films achieves the delivery of biomolecules with a high spatiotemporal resolution. In this study, we reviewed the methods and recent innovations in multilayer cell coatings that demonstrate a strong potential for applications in biomolecule loading, cell patterning, and biosensors.

Expanding severe acute respiratory infection (SARI) surveillance beyond influenza: The process and data from 1 year of implementation in Vietnam.

BACKGROUND: In 2016, as a component of the Global Health Security Agenda, the Vietnam Ministry of Health expanded its existing influenza sentinel surveillance for severe acute respiratory infections (SARI) to include testing for 7 additional viral respiratory pathogens. This article describes the steps taken to implement expanded SARI surveillance in Vietnam and reports data from 1 year of expanded surveillance. METHODS: The process of expanding the suite of pathogens for routine testing by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) included laboratory trainings, procurement/distribution of reagents, and strengthening and aligning SARI surveillance epidemiology practices at sentinel sites and regional institutes (RI). RESULTS: Surveillance data showed that of 4003 specimens tested by the RI laboratories, 20.2% (n = 810) were positive for influenza virus. Of the 3193 influenza-negative specimens, 41.8% (n = 1337) were positive for at least 1 non-influenza respiratory virus, of which 16.2% (n = 518), 13.4% (n = 428), and 9.6% (n = 308) tested positive for respiratory syncytial virus, rhinovirus, and adenovirus, respectively. CONCLUSIONS: The Government of Vietnam has demonstrated that expanding respiratory viral surveillance by strengthening and building upon an influenza platform is feasible, efficient, and practical.

Lp(a) (Lipoprotein(a)) Levels Predict Progression of Carotid Atherosclerosis in Subjects With Atherosclerotic Cardiovascular Disease on Intensive Lipid Therapy: An Analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) Carotid Magnetic Resonance Imaging Substudy-Brief Report.

OBJECTIVE: To assess whether Lp(a) (lipoprotein(a)) levels and other lipid levels were predictive of progression of atherosclerosis burden as assessed by carotid magnetic resonance imaging in subjects who have been treated with LDL-C (low-density lipoprotein cholesterol)-lowering therapy and participated in the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes). APPROACH AND RESULTS: AIM-HIGH was a randomized, double-blind study of subjects with established vascular disease, elevated triglycerides, and low HDL-C (high-density lipoprotein cholesterol). One hundred fifty-two AIM-HIGH subjects underwent both baseline and 2-year follow-up carotid artery magnetic resonance imaging. Plaque burden was measured by the percent wall volume (%WV) of the carotid artery. Associations between annualized change in %WV with baseline and on-study (1 year) lipid variables were evaluated using multivariate linear regression and the Bonferroni correction to account for multiple comparisons. Average %WV at baseline was 41.6±6.8% and annualized change in %WV over 2 years ranged from -3.2% to 3.7% per year (mean: 0.2±1.1% per year; P=0.032). Increases in %WV were significantly associated with higher baseline Lp(a) (ß=0.34 per 1-SD increase of Lp(a); 95% confidence interval, 0.15-0.52; P<0.001) after adjusting for clinical risk factors and other lipid levels. On-study Lp(a) had a similar positive association with %WV progression (ß=0.33; 95% confidence interval, 0.15-0.52; P<0.001). CONCLUSIONS: Despite intensive lipid therapy, aimed at aggressively lowering LDL-C to <70 mg/dL, carotid atherosclerosis continued to progress as assessed by carotid magnetic resonance imaging and that elevated Lp(a) levels were independent predictors of increases in atherosclerosis burden.

Utility of 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines in HIV-Infected Adults With Carotid Atherosclerosis.

BACKGROUND: Although HIV is associated with increased atherosclerotic cardiovascular disease (CVD) risk, it is unknown whether guidelines can identify HIV-infected adults who may benefit from statins. We compared the 2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III recommendations in HIV-infected adults and evaluated associations with carotid artery intima-media thickness and plaque. METHODS AND RESULTS: Carotid artery intima-media thickness was measured at baseline and 3 years later in 352 HIV-infected adults without clinical atherosclerotic CVD and not on statins. Plaque was defined as IMT >1.5 mm in any segment. At baseline, the median age was 43 (interquartile range, 39-49), 85% were men, 74% were on antiretroviral medication, and 50% had plaque. The American College of Cardiology/American Heart Association guidelines were more likely to recommend statins compared with the Adult Treatment Panel III guidelines, both overall (26% versus 14%; P<0.001), in those with plaque (32% versus 17%; P=0.0002), and in those without plaque (16% versus 7%; P=0.025). In multivariable analysis, older age, higher low-density lipoprotein cholesterol, pack per year of smoking, and history of opportunistic infection were associated with baseline plaque. Baseline IMT (hazard ratio, 1.18 per 10% increment; 95% confidence interval, 1.05-1.33; P=0.005) and plaque (hazard ratio, 2.06; 95% confidence interval, 1.02-4.08; P=0.037) were each associated with all-cause mortality, independent of traditional CVD risk factors. CONCLUSIONS: Although the American College of Cardiology/American Heart Association guidelines recommended statins to a greater number of HIV-infected adults compared with the Adult Treatment Panel III guidelines, both failed to recommend therapy in the majority of HIV-affected adults with carotid plaque. Baseline carotid atherosclerosis but not atherosclerotic CVD risk scores was an independent predictor of mortality. HIV-specific guidelines that include detection of subclinical atherosclerosis may help to identify HIV-infected adults who are at increased atherosclerotic CVD risk and may be considered for statins.

Mortality reduction in patients treated with long-term intensive lipid therapy: 25-year follow-up of the Familial Atherosclerosis Treatment Study-Observational Study.

BACKGROUND: Cardiovascular disease (CVD) begins early in life and is associated with both the number of risk factors present and length of exposure to these risk factors including hyperlipidemia. OBJECTIVES: The clinical benefit of intensive lipid therapy over 25 years was investigated in the Familial Atherosclerosis Treatment Study-Observational Study. METHODS: Of 175 coronary artery disease subjects with mean low-density lipoprotein cholesterol (LDL-C) of 191 mg/dL and mean age of 50 years, who completed the randomized and placebo-controlled Familial Atherosclerosis Treatment Study, 100 chose receiving lipid management by their physicians (usual care [UC]) and 75 elected to receive an intensive treatment [IT] for lipid management with lovastatin (40 mg/d), niacin (2.5 g/d), and colestipol (20 g/d) from 1989 to 2004, followed by double therapy with simvastatin (40-80 mg/d) and niacin from 2005 to 2006 and by triple therapy of ezetimibe 10 mg and simvastatin 40 to 80 mg/d plus niacin during 2007 to 2012. Deaths from CVD, non-CVD, and any cause were compared between UC and IT using Cox proportional hazards model. RESULTS: UC and IT groups were similar in risk factors with the exception that IT had more severe coronary artery disease. Mean LDL-C levels were 167 mg/dL from 1988 to 2004, 97 from 2005 to 2006, and 96 from 2007 to 2012 in surviving subjects receiving UC. IT lowered LDL-C to 119, 97, and 83 mg/dL in the 3 periods, respectively. Compared with UC, IT significantly reduced total mortality (11.1 vs 26.3 per 1000 person years [PY], hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.26-0.77, P = .003) and CVD mortality (10.6 vs 27.7 per 1000 PY, HR = 0.34, 95% CI: 0.15-0.80, P = .009). The non-CVD mortality was also reduced but was not of statistical significance (6.8 vs 12.7 per 1000 PY, HR = 0.55, 95% CI: 0.27-1.14, P = .11). CONCLUSIONS: Long-term intensive lipid therapy significantly reduced total and cardiovascular mortality in Familial Atherosclerosis Treatment Study-Observational Study. These results support the importance of lifetime risk management to improve long-term outcome.

BPTF transduces MITF-driven prosurvival signals in melanoma cells.

Microphthalmia-associated transcription factor (MITF) plays a critical and complex role in melanocyte transformation. Although several downstream targets of MITF action have been identified, the precise mechanisms by which MITF promotes melanocytic tumor progression are incompletely understood. Recent studies identified an oncogenic role for the bromodomain plant homeodomain finger transcription factor (BPTF) gene in melanoma progression, in part through activation of BCL2, a canonical target of MITF signaling. Analysis of the BPTF promoter identified a putative MITF-binding site, suggesting that MITF may regulate BPTF expression. Overexpression of MITF resulted in up-regulation of BPTF in a panel of melanoma and melanocyte cell lines. shRNA-mediated down-regulation of MITF in melanoma cells was accompanied by down-regulation of BPTF and BPTF-regulated genes (including BCL2) and resulted in reduced proliferative capacity of melanoma cells. The suppression of cell growth mediated by MITF silencing was rescued by overexpression of BPTF cDNA. Binding of MITF to the BPTF promoter was demonstrated using ChIP analysis. MITF overexpression resulted in direct transcriptional activation of BPTF, as evidenced by increased luciferase activity driven by the BPTF promoter. These results indicate that BPTF transduces key prosurvival signals driven by MITF, further supporting its important role in promoting melanoma cell survival and progression.

Tumor suppressor role of microRNA-1296 in triple-negative breast cancer.

UNLABELLED: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis, which lacks effective targeted therapies. There is an urgent need to better understand the underlying molecular mechanisms of TNBC aggressiveness and identify novel, efficient targets for therapeutic intervention. METHODS: miRNA qRT-PCR was used to determine the expression of miR-1296 in cell lines. The miR-1296 overexpression effects in TNBC cell lines were investigated using assays of colony formation, cell cycle and apoptosis. Immunoblotting was performed to determine the expression of the miR-1296 target protein, and luciferase assays were performed to confirm the target of miR-1296 action. RESULTS: miR-1296 expression was significantly suppressed in TNBC cell lines and tissues samples. Overexpression of miR-1296 significantly suppressed cell proliferation of two TNBC cell lines when compared to control miRNA-expressing cells. A significant decrease in the S-phase of the cell cycle was observed following miR-1296 overexpression, accompanied by induction of apoptosis in TNBC cells. Cyclin D1 (CCND1) was identified as a target of miR-1296 action. miR-1296 overexpression significantly suppressed the luciferase activity of reporter plasmid containing the 3'UTR of CCND1 and protein expression levels of CCND1 in TNBC cells. The effects of miR-1296 overexpression on TNBC cell growth were reversed by CCND1 overexpression. miR-1296 expression sensitized TNBC cells to cisplatin treatment. CONCLUSION: Our results demonstrate a novel tumor suppressor role for miR-1296 in triple-negative breast cancer cell lines, identify CCND1 as its target of action, and demonstrate a potential role for miR-1296 in sensitizing breast cancer cells to cisplatin.

Proprotein convertase subtilisin/kexin type 9 inhibition: a new therapeutic mechanism for reducing cardiovascular disease risk.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the regulation of cholesterol homeostasis. By binding to hepatic low-density lipoprotein (LDL) receptors and promoting their lysosomal degradation, PCSK9 reduces LDL uptake, leading to an increase in LDL cholesterol concentrations. Gain-of-function mutations in PCSK9 associated with high LDL cholesterol and premature cardiovascular disease have been causally implicated in the pathophysiology of autosomal-dominant familial hypercholesterolemia. In contrast, the more commonly expressed loss-of-function mutations in PCSK9 are associated with reduced LDL cholesterol and cardiovascular disease risk. The development of therapeutic approaches that inhibit PCSK9 function has therefore attracted considerable attention from clinicians and the pharmaceutical industry for the management of hypercholesterolemia and its associated cardiovascular disease risk. This review summarizes the effects of PCSK9 on hepatic and intestinal lipid metabolism and the more recently explored functions of PCSK9 in extrahepatic tissues. Therapeutic approaches that prevent interaction of PCSK9 with hepatic LDL receptors (monoclonal antibodies, mimetic peptides), inhibit PCSK9 synthesis in the endoplasmic reticulum (antisense oligonucleotides, siRNAs), and interfere with PCSK9 function (small molecules) are also described. Finally, clinical trials testing the safety and efficacy of monoclonal antibodies to PCSK9 are reviewed. These have shown dose-dependent decreases in LDL cholesterol (44%-65%), apolipoprotein B (48%-59%), and lipoprotein(a) (27%-50%) without major adverse effects in various high-risk patient categories, including those with statin intolerance. Initial reports from 2 of these trials have indicated the expected reduction in cardiovascular events. Hence, inhibition of PCSK9 holds considerable promise as a therapeutic option for decreasing cardiovascular disease risk.

Cardiovascular Effects of Exposure to Cigarette Smoke and Electronic Cigarettes: Clinical Perspectives From the Prevention of Cardiovascular Disease Section Leadership Council and Early Career Councils of the American College of Cardiology.

Cardiovascular morbidity and mortality as a result of inhaled tobacco products continues to be a global healthcare crisis, particularly in low- and middle-income nations lacking the infrastructure to develop and implement effective public health policies limiting tobacco use. Following initiation of public awareness campaigns 50 years ago in the United States, considerable success has been achieved in reducing the prevalence of cigarette smoking and exposure to secondhand smoke. However, there has been a slowing of cessation rates in the United States during recent years, possibly caused by high residual addiction or fatigue from cessation messaging. Furthermore, tobacco products have continued to evolve faster than the scientific understanding of their biological effects. This review considers selected updates on the genetics and epigenetics of smoking behavior and associated cardiovascular risk, mechanisms of atherogenesis and thrombosis, clinical effects of smoking and benefits of cessation, and potential impact of electronic cigarettes on cardiovascular health.

Prolonged combination lipid therapy is associated with reduced carotid intima-media thickness: a case-control study of the 20-year Familial Atherosclerosis Treatment - Observational Study (FATS-OS).

BACKGROUND: Studies have documented the short-term vascular benefits of combination lipid therapy. OBJECTIVE: Our objective was to evaluate the long-term effects of combination lipid therapy on carotid intima-media thickness (CIMT) in patients with coronary artery disease. METHODS: We performed a case-control study in patients who had finished the Familial Atherosclerosis Treatment Study (FATS) and returned to usual care with statin therapy alone or had elected to participate in the 20-year FATS-Observational Study (FATS-OS) and received combination therapy with lovastatin (40 mg/day), niacin (2-3 g/day), and colestipol (20 gm/day) for 11 years, then continued with simvastatin (10-80 mg/day) or lovastatin (40-80 mg/day) plus niacin (2-4 g/day). After 17.8 ± 0.8 years with combination therapy and 19.0 ± 0.8 years with usual care, cholesterol levels and CIMT were collected in 43 FATS-OS patients and 26 usual care patients. RESULTS: Combination therapy group had a greater decrease in total cholesterol (-42 ± 14% vs -31 ± 17%, P = .008) and low-density lipoprotein cholesterol (LDL-C) (-57 ± 13% vs -38 ± 25%, P < .001) and greater increase in high-density lipoprotein cholesterol (HDL-C) (38 ± 43% vs 15 ± 23%, P = .02) as compared with usual care. CIMT (0.902 ± 0.164 vs 1.056 ± 0.169 mm, P < .001) on intensive therapy was significantly less compared with usual care. Multivariate regression analysis (coefficient, 95% CI) showed that combination therapy (-0.13; -0.21 to -0.04, P = .003) and on-therapy LDL-C (0.15; 0.02 to 0.28, P = .03) were significant independent predictors of CIMT. CONCLUSIONS: Prolonged combination lipid therapy is associated with greater improvements in LDL-C and HDL-C levels and less atherosclerotic burden as compared with statin therapy alone.

Lipid-lowering therapy in patients 75 years and older: clinical priority or superfluous therapy?

The incidence and prevalence of cardiovascular (CV)-related morbidity and mortality significantly increase with age. In the elderly, hypercholesterolemia with elevated total and low-density-lipoprotein cholesterol is a significant predictor of incident and recurrent CV disease. Multiple lines of evidence have established the benefit of statin therapy to lower cholesterol levels and reduce the risk of CV events as well as prevent progression of subclinical atherosclerotic disease. Elderly patients, particularly those older than 75 years, have not been well represented in randomized clinical trials evaluating lipid lowering therapy. The limited available data from clinical trials do support the benefit of statin therapy in the elderly population. Based upon these data, cholesterol treatment guidelines endorse statin therapy as the primary treatment of hypercholesterolemia in elderly patients, though caution is recommended given the greater number of co-morbid conditions and concern for poly-pharmacy common in the elderly. Additional research is needed to better establish the benefit of statin therapy in the elderly within the context of reducing CV risk, minimizing side effects, and improving overall quality of life.

Dyslipidemia in women: etiology and management.

Dyslipidemia is highly prevalent among women. The management of dyslipidemia is a cornerstone in the prevention of both primary and secondary cardiovascular events, such as myocardial infarction, ischemic stroke, and coronary death. All major international guidelines on the treatment of dyslipidemia recommend similar approaches to the management of dyslipidemia in both men and women. Estrogen replacement therapy should not be considered as a therapeutic option for managing dyslipidemia in women. The reduction of atherogenic lipoprotein burden (reducing low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol based on risk-stratified thresholds and treatment targets) provided the framework for managing dyslipidemia in the US, Europe, Canada, and elsewhere in the world. Very recently, new guidelines in the US have changed this paradigm, whereby rather than focusing on treatment targets, risk now defines the intensity of treatment with statin therapy, with no specific goals for what level of low-density lipoprotein cholesterol should be attained. It is not clear if this will lead to changes in lipid guidelines in other parts of the world. In the meantime, region-specific guidelines should be followed. Lipid lowering with statin therapy does correlate with reductions in cardiovascular event rates in women. The clinical impact of treating dyslipidemias in women with nonstatin drugs (eg, fibrates, nicotinic acid, bile acid-binding resins, omega-3 fish oils) is as yet not determined.