Management of Dyslipidemia in Patients with Hypertension,Diabetes, and Metabolic Syndrome

Purpose of Review

The purpose of this review is to discuss dyslipidemia in the various common clinical conditions including hypertension, diabetes mellitus, and metabolic syndrome and review the current therapeutic strategy in these settings.

Recent Findings

Dyslipidemias are common in patients with hypertension, diabetes mellitus, and metabolic syndrome. Epidemiologic studies have shown a strong correlation between serum lipid levels and risk of atherosclerotic cardiovascular disease. Multifactorial intervention strategies aimed at controlling lipids, blood pressure, and blood glucose simultaneously achieve maximal reductions in cardiovascular risk.

Summary

Dyslipidemia and metabolic abnormalities are strongly associated with atherosclerosis and worse cardiovascular outcomes. While pharmacotherapy with statins has been proven to be beneficial for dyslipidemia, lifestyle modification emphasizing weight loss and regular exercise is an essential component of the interventional strategy. The common thread underlying atherosclerosis and metabolic abnormalities is endothelial dysfunction. Improved understanding of the role of endothelium in health and disease can potentially lead to novel therapies that may preempt development of atherosclerosis and its complications.

     

Sex, age, and regional differences in L-type calcium current are important determinants of arrhythmia phenotype in rabbit hearts with drug-induced long QT type 2

In congenital and acquired long QT type 2, women are more vulnerable than men to torsade de pointes. In prepubertal rabbits (and children), the arrhythmia phenotype is reversed; however, females still have longer action potential durations than males. Thus, sex differences in K(+) channels and action potential durations alone cannot account for sex-dependent arrhythmia phenotypes. The L-type calcium current (I(Ca,L)) is another determinant of action potential duration, Ca(2+) overload, early afterdepolarizations (EADs), and torsade de pointes. Therefore, sex, age, and regional differences in I(Ca,L) density and in EAD susceptibility were analyzed in epicardial left ventricular myocytes isolated from the apex and base of prepubertal and adult rabbit hearts. In prepubertal rabbits, peak I(Ca,L) at the base was 22% higher in males than females (6.4+/-0.5 versus 5.0+/-0.2 pA/pF; P<0.03) and higher than at the apex (6.4+/-0.5 versus 5.0+/-0.3 pA/pF; P<0.02). Sex differences were reversed in adults: I(Ca,L) at the base was 32% higher in females than males (9.5+/-0.7 versus 6.4+/-0.6 pA/pF; P<0.002) and 28% higher than the apex (9.5+/-0.7 versus 6.9+/-0.5 pA/pF; P<0.01). Apex-base differences in I(Ca,L) were not significant in adult male and prepubertal female hearts. Western blot analysis showed that Ca(v)1.2alpha levels varied with sex, maturity, and apex-base, with differences similar to variations in I(Ca,L); optical mapping revealed that the earliest EADs fired at the base. Single myocyte experiments and Luo-Rudy simulations concur that I(Ca,L) elevation promotes EADs and is an important determinant of long QT type 2 arrhythmia phenotype, most likely by reducing repolarization reserve and by enhancing Ca(2+) overload and the propensity for I(Ca,L) reactivation.     

Lipid abnormalities in coronary heart disease: a population-based case-control study

BACKGROUND: We performed a case-control study to estimate lipid-cholesterol fractions in patients with coronary heart disease and compared them with population-based controls. METHODS AND RESULTS: A total of 635 newly diagnosed patients with coronary heart disease (518 males and 117 females) and 632 subjects (346 males and 286 females) obtained from an ongoing urban coronary heart disease risk factor epidemiological study were evaluated. Age-specific lipid values (total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, and total:high-density lipoprotein cholesterol ratio) were compared using the t-test. Age-adjusted prevalence of dyslipidemia as defined by the US National Cholesterol Education Program was compared using the Chi-square test. In all the age groups, and in both males and females, levels of total and low-density lipoprotein cholesterol were not significantly different. In males, the high-density lipoprotein cholesterol (mg/dl) was significantly lower in patients with coronary heart disease as compared to controls in the age groups 30-39 years (35.1+/-11 v. 43.7+/-9), 40-49 years (39.0+/-10 v. 47.1+/-8), 50-59 years (38.9+/-11 v. 43.8+/-9) and 60-69 years (38.6+/-11, v. 42.8+/-7) (p<0.05). In females, high-density lipoprotein cholesterol was less in the age groups 30-39 years (30.2+/-9 v. 40.7+/-9), 50-59 years (39.7+/-12 v. 44.7+/-8) and 60-69 years (35.6+/-11 v. 42.2+/-9). The level of triglycerides was significantly higher in male patients in the age groups 40-49 years (195.3+/-96 v. 152.8+/-78), 50-59 years (176.7+/-76 v. 162.9+/-97), 60-69 years (175.5+/-93 v. 148.1+/-65) and >70 years (159.8+/-62 v. 100.0+/-22); and in female patients in the age group 30-39 years (170.8+/-20 v. 149.9+/-9) (p<0.05). The total:high-density lipoprotein cholesterol ratio was significantly higher in all age groups in male as well as female patients with coronary heart disease (p<0.05). CONCLUSIONS: An age-adjusted case-control comparison showed that the prevalence of hypertension, diabetes, high total cholesterol (> or =200 mg/dl) (males 48.8% v. 20.2%; females 59.8% v. 33.4%) and high low-density lipoprotein cholesterol (> or =130 mg/dl) (males 42.1% v. 15.0%; females 52.1% v. 31.0%) was significantly more in cases than in controls. The prevalence of low high-density lipoprotein cholesterol (<35 mg/dl) (males 39.6% v. 6.2%; females 39.3% iv 9.5%), high total:high-density lipoprotein ratio (> or = 5.0) and high triglycerides (> or =200 mg/ dl: males 39.6%, v. 10.2%; females 17.1% v. 11.9%) was also significantly higher in cases (p<0.05).     

Increased expression of CYR61, an extracellular matrix signaling protein, in human benign prostatic hyperplasia and its regulation by lysophosphatidic acid

Lysophosphatidic acid (LPA) is an endogenous lipid growth factor that is thought to play important roles in cell proliferation and antiapoptosis and therefore may have roles in the development and progression of benign prostatic hyperplasia (BPH). CYR61 (CCN1), on the other hand, is a growth factor-inducible immediate early gene that functions in cell proliferation, differentiation, and extracellular matrix synthesis. Here we show the close relationship between LPA-induced expression of CYR61 and prostate enlargement. CYR61 mRNA and protein were dramatically up-regulated by 18:1 LPA (oleoyl-LPA) within 1 and 2 h, respectively, in both stromal and epithelial prostatic cells. G protein-coupled receptors, i.e. Edg-2, Edg-4, and Edg-7, for LPA were also expressed in both stromal and epithelial prostatic cells. Furthermore, on DNA microarray analysis for normal and BPH patients, CYR61 was found to be related to the development and progression of BPH, regardless of symptoms. Although CYR61 mRNA was synthesized in hyperplastic epithelial cells, in many cases of BPH, CYR61 protein was detected in both the epithelial and stromal regions of BPH patient tissues. The functional contribution of CYR61 to prostatic cell growth was demonstrated by recombinant CYR61 protein and anti-CYR61 neutralizing antibodies, which inhibited CYR61-dependent cell spreading and significantly diminished cell proliferation, respectively. In conclusion, these data support the hypothesis that LPAs induce the expression of CYR61 by activating G proteincoupled receptors and that CYR61 acts as a secreted autocrine and/or paracrine mediator in stromal and epithelial hyperplasia, demonstrating the potential importance of this signaling mechanism in the disease.     

Twenty-four-hour secretion patterns of luteinizing hormone in mithuns (Bos frontalis)

A 24 h secretion pattern of luteinizing hormone (LH) was not available in mithun (Bos frontalis), a semi-wild ruminant. To characterize the 24 h LH profiles, six female mithun calves (age 7.8 +/- 0.5 months and 102.5 +/- 5.6 kg; group I) and six female mithuns averaging 25.4 months of age and 240 kg (group II) were selected from the National Research Centre on Mithun farm and were maintained in semi-intensive systems. Blood samples collected from all the animals at 30 min intervals for 24h were assayed for plasma LH. Plasma progesterone was also estimated in twice-a-week samples collected for 6-week period preceding each 24h sampling to assess whether any animal had begun ovarian cyclicity. The body weights of all animals were also recorded weekly during the 6-week period. LH patterns consisted of frequent pulses of varying amplitude. Luteinizing hormone pulses occurred at an average frequency of 0.28/h ( approximately 7 pulses/24 h) and 0.15/h ( approximately 3.5 pulses/24 h) for mithuns of groups II and I, respectively, the rate did not differ markedly among mithuns within each group but was significantly different between the groups. Similarly, the magnitude of LH secretory pulses did not vary among mithuns within the group but was significantly higher in group II than in group I animals. In group II, the LH peaks averaged 1.59 and 1.00 ng/ml in mithun having the highest and lowest LH peaks, respectively and the corresponding values for group I mithuns were 0.66 and 0.51ng/ml. Mithun with higher peak LH levels also had higher mean LH concentrations (P<0.05). The mithuns of group II had significantly higher plasma progesterone concentration (0.89 +/- 0.02 ng/ml) than those recorded in group I mithuns (0.26 +/- 0.01 ng/ml). Plasma progesterone profiles suggested that no animal reached puberty. In conclusion, there was higher LH secretion with higher pulsatility and greater amplitude in group II mithuns than exhibited in mithuns of group I and the prepubertal mithuns of group II were in approaching puberty, which were also indicated by their plasma progesterone profiles, critical body weight and age required to attain puberty, in addition to higher pulsatility of LH secretion.     

Comparison of structures and energies of CH5(2+*) with CH4(+*) and their possible role in superacidic methane activation

Contrary to previous theoretical studies at the UHF/6-31G* level, the methonium radical dication CH5(2+) is not a Cs symmetrical structure with a 2e-3c bond but a C2v symmetrical structure 1 with two 2e-3c bonds (at the UHF/6-31G**, UMP2/6-31G**, and UQCISD(T)/6-311G** levels). The Cs symmetrical structure is not even a minimum at the higher level of calculations. The four hydrogen atoms in 1 are bonded to the carbon atom by two 2e-3c bonds and the fifth hydrogen atom by a 2e-2c bond. The unpaired electron of 1 is located in a formal p-orbital (of the sp2-hybridized carbon atom) perpendicular to the plane of the molecule. Hydrogen scrambling in 1 is however extremely facile, as is in other C1 cations. It is found that the protonation of methane to CH5(+) decreases the energy for subsequent homolytic cleavage resulting in the exothermic (24.1 kcal/mol) formation of CH4(+*). Subsequent reaction with neutral methane while reforming CH5(+) gives the methyl radical enabling reaction with excess methane to ethane and H2. The overall reaction is endothermic by 11.4 kcal/mol, but offers under conditions of oxidative removal of H2 an alternative to the more energetic carbocationic conversion of methane.     

Upper gastrointestinal mucosal lesions in chronic renal failure.

The upper gastrointestinal mucosa was studied endoscopically in 182 patients (140 males, 42 females) with chronic renal failure prior to hemodialysis. Endoscopy revealed normal mucosa in 77 patients (42.3%), inflammatory mucosal lesions in 88 (48.4%), peptic ulcer in 16 (8.8%; duodenal 15, gastric 1) and Barrett's ulcer in one patient. Upper gastrointestinal bleeding was noted at presentation in 16 (8.8%) cases and was associated with erosive gastritis, duodenitis and duodenal ulcer in 11, 3 and 2 patients respectively. Thus patients with chronic renal failure had a high prevalence of inflammatory mucosal changes.     

Similarities in cyclic vomiting syndrome across age groups

OBJECTIVE: Cyclic vomiting syndrome is well recognized in children yet has poorly defined pathogenesis and treatment. Cyclic vomiting syndrome is occasionally diagnosed in older subjects, but little attempt has been made to determine if such cases represent a unique disorder. METHODS: We reviewed clinical data from 39 patients aged 1.8-75 yr with cyclic vomiting syndrome meeting published criteria for diagnosis. Clinical characteristics were compared between subjects with symptom onset in childhood (<12 yr, n = 18) and subjects with onset at an older age (> or =12 yr, n = 21; mean age at onset 34.8+/-3.8 yr). RESULTS: All patients had stereotypical episodes of vomiting separated by varying symptom-free intervals. The prevalence rates of prodromal symptoms, triggering events, alleviants, associated symptoms including abdominal pain and diarrhea, and past or family history of migraine were similar in the children and older subjects with the syndrome (p > 0.3 for each). Delay in diagnosis was greater in the older subset (3.1+/-0.8 yr vs 7.9+/-3.1 yr, p < 0.05). Interepisode intervals and total number of hospitalizations did not differ significantly between younger and older patients, but duration of episodes was significantly longer in the older group (2.0+/-0.5 days vs 3.8+/-0.4 days, p < 0.01). When subjects were further substratified by age of illness onset, duration of episodes progressively increased from infant/toddlers (1.8+/-0.4 days) through childhood (2.3+/-0.5 days) and adolescence (2.9+/-1.0 days) and into adulthood (3.9+/-0.5; p < 0.05 across groups). Episode duration did not lengthen further in subgroups >20 yr of age. CONCLUSIONS: Many characteristics of cyclic vomiting syndrome are similar irrespective of age at disorder onset, suggesting a uniform pathogenesis. Duration of episodes increases with age to age 20 yr. Increased awareness of the condition and a high index of suspicion may help decrease delay in diagnosis after symptom onset.     

Utilization of Anthocyanins-Rich Extract from Banana Bract in the Green Synthesis of AgNPs with Anti-proliferative Potential

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Present study was undertaken to optimize the extraction conditions for the recovery of anthocyanins from an...