Diabetes, hyperlipidemia, and hypertension are modifiable risk factors that predict cardiovascular disease events. The effect of these risk factors on incident cardiovascular disease increases with progressively higher levels of glucose, low-density lipoprotein cholesterol, and blood pressure. The thresholds for initiating treatment of these modifiable risk factors and the optimal goals of risk factor modification are a focus of primary prevention research. Although an aggressive approach is appealing, adverse events may occur, and potential physiological barriers may exist. This paper discusses primary prevention of coronary heart disease that may be achieved through modification of diabetes, hyperlipidemia, and hypertension by summarizing current guidelines and pertinent clinical trial data from intervention trials that included a primary prevention cohort.
OBJECTIVE: To ascertain whether persons treated with statins experience a decreased risk of community-acquired Staphylococcus aureus bacteremia (CA-SAB) as compared with nonusers.
PATIENTS AND METHODS: Using population-based medical registries, we conducted a case-control study including all adults with first-time CA-SAB and population controls matched on age, sex, and residence in Northern Denmark from January 1, 2000, through December 31, 2011. Statin users were categorized as current users (new or long-term use), former users, and nonusers. We used conditional logistic regression to compute odds ratios (ORs) for CA-SAB according to statin exposure, overall and stratified by intensity (<20, 20-39, ≥40 mg/d) and duration of use (<365, 365-1094, ≥1095 days).
RESULTS: We identified 2638 patients with first-time CA-SAB and 26,379 matched population controls. Compared with nonusers, current statin users experienced markedly decreased risk of CA-SAB (adjusted OR, 0.73; 95% CI, 0.63-0.84). The adjusted OR was 0.96 (95% CI, 0.60-1.51) for new users, 0.71 (95% CI, 0.62-0.82) for long-term users, and 1.12 (95% CI, 0.94-1.32) for former users as compared with nonusers. The CA-SAB risk decreased with increasing intensity of statin use; thus, compared with nonusers, the adjusted OR was 0.84 (95% CI, 0.68-1.04) for current users with daily dosages of less than 20 mg/d, 0.71 (95% CI, 0.58-0.87) for 20 to 39 mg/d, and 0.63 (95% CI, 0.49-0.81) for 40 mg/d or more. Conversely, we observed no differences in the risk of CA-SAB with successive increases in the duration of statin use.
CONCLUSION: Statin use was associated with a decreased risk of CA-SAB, particularly in long-term users.
Fasting for >8 h, as previously required for lipid profiles, normally only occurs a few hours before breakfast. By contrast, the nonfasting state predominates most of a 24-h cycle and better captures atherogenic lipoprotein levels. Plasma contains atherogenic lipoproteins of hepatic origin in the fasting state and additionally those of intestinal origin in the nonfasting state. Maximal mean changes for random, nonfasting versus fasting levels are +26 mg/dl for triglycerides, -8 mg/dl for total cholesterol, -8 mg/dl for low-density lipoprotein cholesterol, +8 mg/dl for remnant cholesterol, and -8 mg/dl for non-high-density lipoprotein cholesterol; lipoprotein(a), apolipoprotein B, and high-density lipoprotein cholesterol are largely unaffected. For patients, laboratories, and clinicians alike, nonfasting lipid profiles represent a simplification without negative implications for prognostic, diagnostic, and therapeutic options for cardiovascular disease prevention. Several societies' guidelines and statements in Denmark, the United Kingdom, Europe, Canada, Brazil, and the United States endorse nonfasting lipid profiles.
Cardiovascular Diseases (3) Cardiovascular Diseases (3), Dyslipidemias (1), more mentions
BACKGROUND: Few long-term or controlled studies of bariatric surgery have been conducted to date. We report the 12-year follow-up results of an observational, prospective study of Roux-en-Y gastric bypass that was conducted in the United States.
METHODS: A total of 1156 patients with severe obesity comprised three groups: 418 patients who sought and underwent Roux-en-Y gastric bypass (surgery group), 417 patients who sought but did not undergo surgery (primarily for insurance reasons) (nonsurgery group 1), and 321 patients who did not seek surgery (nonsurgery group 2). We performed clinical examinations at baseline and at 2 years, 6 years, and 12 years to ascertain the presence of type 2 diabetes, hypertension, and dyslipidemia.
RESULTS: The follow-up rate exceeded 90% at 12 years. The adjusted mean change from baseline in body weight in the surgery group was -45.0 kg (95% confidence interval [CI], -47.2 to -42.9; mean percent change, -35.0) at 2 years, -36.3 kg (95% CI, -39.0 to -33.5; mean percent change, -28.0) at 6 years, and -35.0 kg (95% CI, -38.4 to -31.7; mean percent change, -26.9) at 12 years; the mean change at 12 years in nonsurgery group 1 was -2.9 kg (95% CI, -6.9 to 1.0; mean percent change, -2.0), and the mean change at 12 years in nonsurgery group 2 was 0 kg (95% CI, -3.5 to 3.5; mean percent change, -0.9). Among the patients in the surgery group who had type 2 diabetes at baseline, type 2 diabetes remitted in 66 of 88 patients (75%) at 2 years, in 54 of 87 patients (62%) at 6 years, and in 43 of 84 patients (51%) at 12 years. The odds ratio for the incidence of type 2 diabetes at 12 years was 0.08 (95% CI, 0.03 to 0.24) for the surgery group versus nonsurgery group 1 and 0.09 (95% CI, 0.03 to 0.29) for the surgery group versus nonsurgery group 2 (P<0.001 for both comparisons). The surgery group had higher remission rates and lower incidence rates of hypertension and dyslipidemia than did nonsurgery group 1 (P<0.05 for all comparisons).
CONCLUSIONS: This study showed long-term durability of weight loss and effective remission and prevention of type 2 diabetes, hypertension, and dyslipidemia after Roux-en-Y gastric bypass. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
Endocrine Disorders (7), Cardiovascular Diseases (4), Anti-Obesity and Weight Loss (4) Diabetes Mellitus, Type 2 (6), Dyslipidemias (4), Hypertension (4), more mentions
Elevated free thyroxine (FT4) levels may play a protective role in development of dyslipidemia. However, few prospective studies have been performed to definite the effects of thyroid hormones on the improvement of dyslipidemia and its components. Thus, this study aims to clarify the association between thyroid hormones within normal range and reversal of dyslipidemia in the absence of intervention.A prospective analysis including 134 adult males was performed between 2010 and 2014. Anthropometric parameters, thyroid function, and lipid profile were measured at baseline and during follow-up. Logistic regression and receiver operating characteristic (ROC) analysis were conducted to identify the variables in forecasting the reversal of dyslipidemia and its components.During 4.5-year follow-up, 36.6% (49/134) patients resolved their dyslipidemia status without drug intervention. Compared with the continuous dyslipidemia group, subjects in reversal group had elevated FT4 and high-density lipoprotein cholesterol (HDL-C) levels, as well as decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels at baseline. Furthermore, baseline FT4 is negatively associated with the change percentages of TG (r = -0.286, P = .001), while positively associated with HDL-C (r = 0.227, P = .008). However, no correlation of lipid profile change percentages with FT3 and TSH were observed. Furthermore, the improving effects of baseline FT4 on dyslipidemia, high TG, and low HDL-C status were still observed after multivariable adjustment. In ROC analysis, areas under curve (AUCs) for FT4 in predicting the reversal of dyslipidemia, high TG, and low HDL-C were 0.666, 0.643, and 0.702, respectively (P = .001 for dyslipidemia, .018 for high TG, and .001 for low HDL-C).Higher FT4 value within normal range may ameliorate the dyslipidemia, especially high TG and low HDL-C status, in males without drug intervention. This suggests that a more flexible lipid-lowering therapy may be appropriate for patients with high-normal FT4.
Blood Disorders and Hematology (11) Dyslipidemias (12), more mentions
Context: Familial partial lipodystrophy type 1 (FPLD1) is an extreme form of central adiposity, with peripheral lipodystrophy associated with severe manifestations of the metabolic syndrome, often poorly responsive to standard therapeutic approaches. Body mass index in FPLD1 varies but, in many cases, is below the level at which metabolic surgery is usually considered as a therapeutic option.
Design: We detailed the metabolic response to gastric bypass surgery of three patients with FPLD1, refractory to medical therapy.
Results: Roux-en-Y gastric bypass (RYGB) was associated with weight loss and substantial improvements in glycemic control and insulin sensitivity. All three patients were able to stop using insulin. Glucose tolerance testing in one patient demonstrated an increase in L-cell-derived gut hormone responses postoperatively.
Conclusion: RYGB surgery substantially improved glycemic control in three patients with FPLD1, two of whom had body mass indices below 30 kg/m2. RYGB should be considered in patients with partial lipodystrophy and refractory metabolic disease.
Anti-Obesity and Weight Loss (3) Lipodystrophy (3), Familial Partial Lipodystrophy (2), Obesity (1), more mentions
Objectives: The prevalence of atherosclerotic risk factors and disease in Takayasu's arteritis (TAK) has not been well defined. We aimed to assess the frequency of cardiovascular (CV) risk factors and the incidence of CV events (CVEs) in patients with TAK from two ethnically different populations.
Methods: Patients with TAK followed at Mayo Clinic, Rochester, MN, USA and Marmara University, Istanbul, Turkey were included in this retrospective study. Patients with TAK were compared with age-, sex- and calendar year-matched controls from the same geographical region without TAK. The 2008 Framingham 10-year general CV risk score (FRS) was used for the evaluation of CV risk at the time of TAK incidence/index date.
Results: In total, 191 patients with TAK and 191 non-TAK controls were included. Hypertension and the prevalence of lipid-lowering treatments were significantly more frequent in TAK. Prior to the incidence/index date, occurrence of CVE was significantly higher in TAK. The FRS was significantly higher in TAK compared with non-TAK at incidence/index date. The cumulative incidence of CVE was 15.4% at 10 years in TAK vs 5.8% in non-TAK; the risk of CVE was increased among patients with TAK (hazard ratio = 4.36; 95% CI: 1.25, 15.13).
Conclusion: CV risk factors are more common in patients with TAK, particularly hypertension. The FRS is higher in patients with TAK at the time of diagnosis. The cumulative incidence of CVE was also significantly higher during follow-up in TAK. Our results suggest that patients with TAK should undergo careful assessment of CV risk factors, and an aggressive risk modification approach is warranted.
Cardiovascular Diseases (4), Anti-Obesity and Weight Loss (2), Endocrine Disorders (1) Takayasu Arteritis (3), Hypertension (3), Kidney Failure (1), more mentions
BACKGROUND AND PURPOSE: The visual analogue scale is a self-reported, validated tool to measure quality of life (QoL). Our purpose was to determine whether baseline QoL predicted strokes in the ALLHAT study (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) and evaluate determinants of poststroke change in QoL. In the ALLHAT study, among the 33 357 patients randomized to treatment arms, 1525 experienced strokes; 1202 (79%) strokes were nonfatal. This study cohort includes 32 318 (97%) subjects who completed the baseline visual analogue scale QoL estimate.
METHODS: QoL was measured on a visual analogue scale and adjusted using a Torrance transformation (transformed QoL [TQoL]). Kaplan-Meier curves and adjusted proportional hazards analyses were used to estimate the effect of TQoL on the risk of stroke, on a continuous scale (0-1) and by quartiles (≤0.81, >0.81≤0.89, >0.89≤0.95, >0.95). We analyzed the change from baseline to first poststroke TQoL using adjusted linear regression.
RESULTS: After adjusting for multiple stroke risk factors, the hazard ratio for stroke events for baseline TQoL was 0.93 (95% confidence interval, 0.89-0.98) per 0.1 U increase. The lowest baseline TQoL quartile had a 20% increased stroke risk (hazard ratio=1.20 [95% confidence interval, 1.00-1.44]) compared with the reference highest quartile TQoL. Poststroke TQoL change was significant within all treatment groups (P≤0.001). Multivariate regression analysis revealed that baseline TQoL was the strongest predictor of poststroke TQoL with similar results for the untransformed QoL.
CONCLUSIONS: The lowest baseline TQoL quartile had a 20% higher stroke risk than the highest quartile. Baseline TQoL was the only factor that predicted poststroke change in TQoL.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.
We looked retrospectively at the 3- to 5-year progression of mild, asymptomatic carotid artery stenosis (CAS). A random sample of 600 patients who had undergone at least two carotid artery duplex ultrasounds between 31 October 2006 and 1 November 2016 with a second duplex ⩾3 and ⩽5 years following the initial one were screened for inclusion. Internal carotid arteries (ICAs) were included if they had 20-49% stenosis on the initial duplex, with 440 carotid arteries meeting this criteria. Analyses were performed utilizing chi-squared and two-tailed t-tests. Twenty-four (5.45%) of the initial 440 carotid arteries progressed to moderate CAS. There was a statistically significant increase in the prevalence of hypertension (68% vs 47%, p=0.022) and diabetes mellitus (44% vs 22%, p=0.008) in patients with carotids that progressed to moderate CAS. There was a decrease in moderate-intensity statin use (32% vs 58%, p=0.005) and an increase in patients not on statins (36% vs 11%, p=0.001) in the group of carotids that progressed to moderate CAS. One carotid artery (0.2%) progressed from mild CAS to severe CAS. If supported by others, our data may lead to a change in the recommendations regarding appropriate follow-up of asymptomatic CAS.
Nonalcoholic fatty liver disease (NAFLD) is becoming the major chronic liver disease in many countries. Its pathogenesis is multifactorial but twin and familial studies indicate significant heritability, which is not fully explained by currently-known genetic susceptibility loci. Notably, mutations in genes encoding nuclear lamina proteins, including lamins, cause lipodystrophy syndromes that include NAFLD. We hypothesized that variants in lamina-associated proteins predispose to NAFLD and used a candidate gene-sequencing approach to test for variants in 10 nuclear lamina-related genes in a cohort of 37 twin and sibling pairs: 21 individuals with, and 53 without, NAFLD. Twelve heterozygous sequence variants were identified in four lamina-related genes (ZMPSTE24/TMPO/SREBF1/SREBF2). The majority of NAFLD patients (>90%) had at least one variant, compared to <40% of controls (P<0.0001). When only insertions/deletions and changes in conserved residues were considered, the difference between the groups was similarly striking (>80% versus <25%; P<0.0001). Presence of a lamina variant segregated with NAFLD independent of the PNPLA3 I148M polymorphism. Several variants were found in TMPO, which encodes the lamina-associated polypeptide-2 (LAP2) that has not previously been associated with liver disease. One of these, a frameshift insertion that generates truncated LAP2, abrogated lamin-LAP2 binding, caused LAP2 mislocalization, altered endogenous lamin distribution, increased lipid droplet accumulation after oleic acid treatment in transfected cells, and led to cytoplasmic association with the ubiquitin-binding protein p62/SQSTM1.
CONCLUSION: Novel variants in nuclear lamina-related genes were identified in a cohort of twins and siblings with NAFLD. One novel variant, which results in a truncated LAP2 protein and a dramatic phenotype in cell culture, represents the first association of TMPO/LAP2 variants with NAFLD and underscores the potential importance of the nuclear lamina in NAFLD. This article is protected by copyright. All rights reserved.
Liver Diseases (2), Fatty Liver (2), Lipodystrophy (1), more mentions
OBJECTIVE: Type 1 and type 2 familial partial lipodystrophies (FPLD) are characterized by the loss or increase of subcutaneous fat in certain body regions, as well as metabolic disorders. Higher muscle volume and mass have also been described. However, so far, possible bone involvement has not been studied. The aim of this study was to evaluate bone mineral density (BMD) in patients with type 1 and type 2 FPLD.
METHODS: A total of 143 women were selected and distributed into three groups (17 women with FPLD2, 82 women with FPLD1 and 44 non-lipodystrophic obese female controls). A thorough history and physical examination were carried out on all subjects, as well as the measurement of anthropometric features. BMD along with fat and fat-free mass (FFM) were determined by DXA (dual-energy X-ray absorptiometry). Statistical analyses, primarily using the χ(2) , ANOVA and ANCOVA tests, were performed, using age, height, fat and FFM as covariables.
RESULTS: After eliminating the possible influences of age, height, fat and FFM, we observed that there were no significant differences in total BMD between patients with FPLD and the control group, showing total BMD values of 1.092 ± 0.037 g/cm(2) in the FPLD2 group, 1.158 ± 0.013 g/cm(2) in the FPLD1 group and 1.173 ± 0.018 g/cm(2) in the control group (p = 0.194). Similarly, no significant differences were found in segmental BMD.
CONCLUSIONS: Unlike in other types of laminopathy in which bone is affected, in the case of FPLD there are no differences in BMD compared to non-lipodystrophic subjects. This article is protected by copyright. All rights reserved.
Muscular and Skeletal Diseases (8), Anti-Obesity and Weight Loss (1) Familial Partial Lipodystrophy (2), more mentions