Nitric oxide (NO
) is critical for functionality of endothelial colony forming cells (ECFCs). Dimerization of endothelial nitric oxide synthase (eNOS) is must to produce NO
and tetrahydrobiopterin ...(BH4) plays a crucial role in stabilizing this state. We investigated BH4 level in ECFCs and its effect on ECFCs functionality in CAD patients. Intracellular biopterin levels and ECFCs functionality in terms of cell viability, adhesion, proliferation, in vitro wound healing and angiogenesis were assessed. Guanosine Triphosphate Cyclohydrolase-1 (GTPCH-1) expression was studied in ECFCs. Serum total reactive oxygen/nitrogen species was measured and effect of nitrosative stress on ECFC's biopterins level and functionality were evaluated by treating with 3-morpholino sydnonimine (SIN-1). BH4 level was significantly lower in ECFCs from CAD patients. Cell proliferation, wound closure reflecting cellular migration as well as in vitro angiogenesis were impaired in ECFCs from CAD patients. Wound healing capacity and angiogenesis were positively correlated with ECFC's BH4. A negative effect of nitrosative stress on biopterins level and cell functionality was observed in SIN-1 treated ECFCs. ECFCs from CAD exhibited impaired functionality and lower BH4 level. Association of BH4 with wound healing capacity and angiogenesis suggest its role in maintaining ECFC's functionality. Oxidative stress may be a determinant of intracellular biopterin levels.
Coronary artery disease (CAD) imposes a significant economic burden in developing countries like India. Timely diagnosis and treatment should be prioritized to mitigate the disease. Current ...diagnostic tools being invasive and less specific raise the need to develop less invasive and more reliable molecular biomarkers. MicroRNAs (miRNAs) are an emerging class of molecules that can serve as a potential source of non-invasive biomarkers for CAD. The objective of this study was to determine the potential of circulatory miRNAs as diagnostic biomarkers in CAD. In this study, we have reported two microRNAs, miR-128-3p and miR-195-5p in the serum of CAD patients in Indian Population. A total of 124 subjects were recruited which included 89 angiographically proven CAD patients and 35 control subjects. Our results show a significant decrease in the levels of miR-128-3p in CAD patients while there were no significant changes in the levels of miR-195-5p. Further bioinformatics analysis revealed the potential role of miR-128-3p in cholesterol homeostasis. Altered homeostasis due to cholesterol accumulation in macrophages is the driving force behind formation of foam cells which in turn accelerates the progression of CAD. Here, we have shown that miR-128-3p increases cholesterol levels in macrophages by decreasing cholesterol efflux in-vitro.
This commentary refers to ‘Multi-organ assessment in mainly non-hospitalized individuals after SARS-CoV-2 infection: The Hamburg City Health Study COVID programme’ by E.L. Petersen et al., ...https://doi.org/10.1093/eurheartj/ehab914 and the discussion piece ‘Attentive follow-up to counter alarmism’ by R. Twerenbold et al.’, https://doi.org/10.1093/eurheartj/ehac165.
Objective
Myocardial iron overload (MIO) in thalassemia major (TM) may cause subclinical left ventricular (LV) dysfunction which manifests with abnormal strain parameters before a decrease in ...ejection fraction (EF). Early detection of MIO using cardiovascular magnetic resonance (CMR)-T2* is vital. Our aim was to assess if CMR feature-tracking (FT) strain correlates with T2*, and whether it can identify early contractile dysfunction in patients with MIO but normal EF.
Methods
One hundred and four consecutive TM patients with LVEF > 55% on echocardiography were prospectively enrolled. Those fulfilling the inclusion criteria underwent CMR, with T2* being the gold standard for detecting MIO. Group 1 included patients without significant MIO (T2* > 20 ms) and group 2 with significant MIO (T2* < 20 ms).
Results
Eighty-six patients (mean age, 17.32 years, 59 males) underwent CMR. There were 68 (79.1%) patients in group 1 and 18 (20.9%) in group 2. Fourteen patients (16.3%) had mild-moderate MIO, and four (4.6%) had severe MIO. Patients in group 2 had significantly lower global radial strain (GRS). Global longitudinal strain (GLS) and global circumferential strain (GCS) did not correlate with T2*. T1 mapping values were significantly lower in patients with T2* < 10 ms than those with T2* of 10–20 ms; however, FT-strain values were not significantly different between these two groups.
Conclusion
CMR-derived GRS, but not GLS and GCS, correlated with CMR T2*. GRS is significantly decreased in TM patients with MIO and normal EF when compared with those without. FT-strain may be a useful adjunct to CMR T2* and maybe an early marker of myocardial dysfunction in TM.
Key Points
• A global radial strain of < 29.3 derived from cardiac MRI could predict significant myocardial iron overload in patients with thalassemia, with a sensitivity of 76.5% and specificity of 66.7%.
• Patients with any myocardial iron overload have significantly lower GRS, compared to those without, suggesting the ability of CMR strain to identify subtle myocardial contractile disturbances.
• T1 and T2 mapping values are significantly lower in those with severe myocardial iron than those with mild-moderate iron, suggesting a potential role of T1 and T2 mapping in grading myocardial iron.
Impaired high-density lipoprotein (HDL) functions are associated with development of coronary artery disease. In this study, we explored the quantitative differences in HDL (i.e. HDL proteome and ...fatty acid profile of HDL phospholipids) underlying the functional deficits associated with acute coronary syndrome (ACS). The relationship between HDL function and composition was assessed in 65 consecutive ACS patients and 40 healthy controls. Cholesterol efflux capacity (CEC) of HDL and lecithin cholesterol acyl transferase (LCAT) activity were significantly lower in patients with ACS compared to controls. In HDL proteome analysis, HDL isolated from ACS individuals was enriched in apolipoprotein C2 (inhibitor of LCAT), apolipoprotein C4 and serum amyloid A proteins and was deficient in apolipoprotein A-I and A-II. The fatty acid profile of HDL phospholipids analyzed using gas chromatography showed significantly lower percentages of stearic acid (17.4 ± 2.4 vs 15.8 ± 2.8,
p
= 0.004) and omega-3 fatty acids eicosapentaenoic acid (1.0 (0.6–1.4) vs 0.7 (0.4–1.0),
p
= 0.009) and docosahexaenoic acid (1.5 ± 0.7 vs 1.3 ± 0.5,
p
= 0.03) in ACS patients compared to controls. Lower percentages of these fatty acids in HDL were associated with higher odds of developing ACS. Our results suggest that distinct phospholipid fatty acid profiles found in HDL from ACS patients could be one of the contributing factors to the deranged HDL functions in these patients apart from the protein content and the inflammatory conditions.
Summary Background Most data on mortality and prognostic factors in patients with heart failure come from North America and Europe, with little information from other regions. Here, in the ...International Congestive Heart Failure (INTER-CHF) study, we aimed to measure mortality at 1 year in patients with heart failure in Africa, China, India, the Middle East, southeast Asia and South America; we also explored demographic, clinical, and socioeconomic variables associated with mortality. Methods We enrolled consecutive patients with heart failure (3695 66% clinic outpatients, 2105 34% hospital in patients) from 108 centres in six geographical regions. We recorded baseline demographic and clinical characteristics and followed up patients at 6 months and 1 year from enrolment to record symptoms, medications, and outcomes. Time to death was studied with Cox proportional hazards models adjusted for demographic and clinical variables, medications, socioeconomic variables, and region. We used the explained risk statistic to calculate the relative contribution of each level of adjustment to the risk of death. Findings We enrolled 5823 patients within 1 year (with 98% follow-up). Overall mortality was 16·5%: highest in Africa (34%) and India (23%), intermediate in southeast Asia (15%), and lowest in China (7%), South America (9%), and the Middle East (9%). Regional differences persisted after multivariable adjustment. Independent predictors of mortality included cardiac variables (New York Heart Association Functional Class III or IV, previous admission for heart failure, and valve disease) and non-cardiac variables (body-mass index, chronic kidney disease, and chronic obstructive pulmonary disease). 46% of mortality risk was explained by multivariable modelling with these variables; however, the remainder was unexplained. Interpretation Marked regional differences in mortality in patients with heart failure persisted after multivariable adjustment for cardiac and non-cardiac factors. Therefore, variations in mortality between regions could be the result of health-care infrastructure, quality and access, or environmental and genetic factors. Further studies in large, global cohorts are needed. Funding The study was supported by Novartis.
Often a single blood pressure (BP) measurement is used to diagnose and manage hypertension in busy clinics. However, repeated BP measurements have been shown to be more representative of the true BP ...status of the individual. Improper measurement of office BP can lead to inaccurate classification, overestimation of a patient's true BP, unnecessary treatment, and misinterpretation of the true prevalence of hypertension. There is no consensus among major guidelines on the number of recommended measurements at a single visit or the method of arriving at final clinic BP reading. The participants of the National Family Health Survey (NFHS-4), a nationwide survey conducted in India from 2015 to 2016, were used for the analysis. The prevalence and median difference in systolic blood pressure (SBP) and diastolic blood pressure (DBP) for single as well as combinations of two or more readings were calculated. Cross-tabulation was used to assess classification of individuals based on first BP reading compared with the mean of two or more BP measurements. There was a 63% higher prevalence of hypertension when only the first reading was considered for diagnosis in comparison to the mean of the second and third readings. A decrease of 3.6 mmHg and 2.4 mm Hg in mean SBP and DBP, respectively, was observed when the mean of the second and third readings was compared to the first reading. In those who are identified to have grade 1 or higher categories of hypertension, we recommend three BP measurements, with the mean of the second and third measurements being the clinic BP.
Routine use of cardiac sympathetic imaging in HF has been limited by the lower availability/sensitivity of radiotracers. This study was aimed to assess the feasibility of 18F-FDOPA (commonly ...available PET-radiotracer) in assessment of cardiac autonomic dysfunction.
Twenty-four controls (46.5 ± 11.1 years, 16men) and 24 patients (43.5 ± 11.0 years, 18men) with diagnosed HF (Framingham-Criteria) underwent cardiac-PET/CT. Region(s) Of Interest were drawn over entire left ventricular myocardium (LV), individual walls, and mediastinum (M). Coefficient of Variation (CV) was calculated from individual wall counts.
HF patients had significantly lower myocardial 18F-FDOPA uptake (P < .001, independent t test) than controls 32.4% ± 9.5% global reduction; highest in apex (39.9% ± 7.0%). A cut-off of LV/M ≤ 1.68 could differentiate patients from controls with sensitivity and specificity of 100% and 95.8%, respectively. LV/M correlated positively with EF (Pearson coefficient = 0.460, P .031). During follow-up, 3 patients were lost to follow-up, 4 died (survival-20.5 ± 4 months), 2 worsened, and 15 remained stable/showed mild improvement. Patients who worsened/died during follow-up had higher CV than those with stable/improving symptoms 0.16 ± 0.05 vs 0.11 ± 0.05, P value .069 (independent t test); Cox regression P = .084.
Myocardial 18F-FDOPA uptake in patients with HF is significantly reduced. Higher reduction is seen in those with lower EF. CV, a maker of regional heterogeneity, is a potential prognostic marker.
Recent studies emphasize the importance of HDL function over HDL cholesterol measurement, as an important risk for cardiovascular diseases (CVD). We compared the HDL function of patients with acute ...coronary syndrome (ACS) and healthy controls.
We measured cholesterol efflux capacity of HDL using THP-1 macrophages labelled with fluorescently tagged (BODIPY) cholesterol. PON1 activities toward paraoxon and phenyl acetate were assessed by spectrophotometric methods.
We recruited 150 ACS patients and 110 controls. The HDL function of all patients during acute phase and at six month follow-up was measured. The mean age of the patients and controls was 51.7 and 43.6 years respectively. The mean HDL cholesterol/apolipoprotein A-I levels (ratio) of patients during acute phase, follow-up and of controls were 40.2 mg/dl/ 112.5 mg/dl (ratio = 0.36), 38.3 mg/dl/ 127.2 mg/dl (ratio = 0.30) and 45.4 mg/dl/ 142.1 mg/dl (ratio = 0.32) respectively. The cholesterol efflux capacity (CEC) of HDL was positively correlated with apolipoprotein A-I levels during acute phase (r = 0.19, p = 0.019), follow-up (r = 0.26, p = 0.007) and of controls (r = 0.3, p = 0.0012) but not with HDL-C levels (acute phase: r = 0.07, p = 0.47; follow-up: r = 0.1, p = 0.2; control: r = 0.02, p = 0.82). Higher levels of cholesterol efflux capacity, PON1 activity and apolipoprotein A-I were associated with lower odds of development of ACS. We also observed that low CEC is associated with higher odds of having ACS if PON1 activity of HDL is also low and vice versa.
ACS is associated with reduced HDL functions which improves at follow-up. The predicted probability of ACS depends upon individual HDL functions and the interactions between them.
High-density lipoprotein (HDL) comprises a heterogeneous group of particles differing in size, density, and composition. HDL cholesterol (HDL-C) levels have long been suggested to indicate ...cardiovascular risk, inferred from multiple epidemiological studies. The failure of HDL-C targeted interventions and genetic studies has raised doubts on the atheroprotective role of HDL-C. The current consensus is that HDL-C is neither a biomarker nor a causative agent of cardiovascular disorders. With better understanding of the complex nature of HDL which comprises a large number of proteins and lipids with unique functions, recent focus has shifted from HDL quantity to HDL quality in terms of atheroprotective functions. The current research is focused on developing laboratory assays to assess HDL functions for cardiovascular risk prediction. Also, HDL mimetics designed based on the key determinants of HDL functions are being investigated to modify cardiovascular risk. Improving HDL functions by altering its composition is the key area of future research in HDL biology to reduce cardiovascular risk.
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