Retrospective analysis of persistent HyperCKemia with or without muscle weakness in a case series from Greece highlights vast DMD variant heterogeneity.

BACKGROUND: Persistent hyperCKemia results from muscle dysfunction often attributed to genetic alterations of muscle-related genes, such as the dystrophin gene (DMD). Retrospective assessment of findings from DMD analysis, in association with persistent HyperCKemia, was conducted. PATIENTS AND METHODS: Evaluation of medical records from 1354 unrelated cases referred during the period 1996-2021. Assessment of data concerning the detection of DMD gene rearrangements and nucleotide variants. RESULTS: A total of 730 individuals (657 cases, 569 of Greek and 88 of Albanian origins) were identified, allowing an overall estimation of dystrophinopathy incidence at ~1:3800 live male births. The heterogeneous spectrum of 275 distinct DMD alterations comprised exon(s) deletions/duplications, nucleotide variants, and rare events, such as chromosome translocation {t(X;20)}, contiguous gene deletions, and a fused gene involving the DMD and the DOCK8 genes. Ethnic-specific findings include a common founder variant in exon 36 ('Hellenic' variant). CONCLUSIONS: Some 50% of hyperCKemia cases were characterized as dystrophinopathies, highlighting that DMD variants may be considered the most common cause of hyperCKemia in Greece. Delineation of the broad genetic and clinical heterogeneity is fundamental for actionable public health decisions and theragnosis, as well as the establishment of guidelines addressing ethical considerations, especially related to the mild asymptomatic patient subgroup.

Cardiovascular morbidity of severe resistant hypertension among treated uncontrolled hypertensives: a 4-year follow-up study.

Data regarding the prognosis of resistant hypertension (RHTN) with respect to its severity is limited. We investigated the cardiovascular risk of severe RHTN in a prospective observational study. A cohort of 1700 hypertensive patient with treated uncontrolled HTN was followed for a mean period of 3.6 ± 1.8 years. At baseline, standard clinical and laboratory workup was performed, including testing for secondary causes of RHT where applicable. Three groups were identified depending on presence of RHTN (office-based uncontrolled HTN under at least three drugs including a diuretic) and levels of office systolic blood pressure (BP): 1187 patients (70%) without RHTN, 313 (18%) with not-severe RHTN (systolic BP < 160 mmHg) and 200 (12%) with severe RHTN (systolic BP ≥ 160 mmHg). Endpoint of interest was cardiovascular morbidity set as the composite of coronary heart disease and stroke. During follow-up, incidence rates of cardiovascular events per 1000 person-years were 7.1 cases in the non-RHTN group, 12.4 cases in the not-severe RHTN group and 18 cases in the severe RHTN group. Unadjusted analysis showed that compared to uncontrolled patients without RHTN, patients with not-severe RHTN exhibited a similar risk but patients with severe RHTN had a significantly higher risk, by 2.5 times (CI: 1.28-4.73, p = 0.007). Even after multivariate adjustment for established risk factors including BP levels and isolated systolic HTN, severe RHTN remained as an independent predictor of the cardiovascular outcome (OR: 2.30, CI: 1.00-5.29, p = 0.05). In conclusion, among treated yet uncontrolled hypertensive patients, severe RHTN exhibits a significantly higher cardiovascular risk indicating the need for prompt management.

Effect of renal sympathetic denervation on short-term blood pressure variability in resistant hypertension: a meta-analysis.

BACKGROUND/OBJECTIVES: Short-term blood pressure variability (BPV) is affected by multiple factors including the sympathetic nervous system drive. Regarding the latter, the novel interventional technology of renal denervation (RDN), by modulating the sympathetic system activation, could have a beneficial impact on BPV. The aim of the current study is to review and meta-analyze the available evidence on the effect of RDN on short-term BPV. METHODS: We searched Medline/PubMed database until October 2016 for studies with eligible content. We performed random-effect meta-analyses for 12 outcomes of interest: the standard deviation (SD) of SBP (24 h, daytime and night-time) and DBP (24 h, daytime and night-time), the weighted SD of SBP and DBP across 24 h, the coefficient of variation of SBP and DBP across 24 h and the average real variability of SBP and DBP across 24 h. RESULTS: RDN reduced the SD of SBP across 24 h [mean change: -1.212 (95% confidence intervals (CIs): -2.354/-0.071), P = 0.037] and decreased the SD of systolic daytime BP [mean difference: -1.617 (95% CIs: -3.21/-0.026), P = 0.046] and diastolic daytime BP (marginally) [mean difference: -2.605 (95% CIs: -5.21/-0.003), P = 0.05]. The effect of RDN in reducing SD of SBP across 24 h or DBP across daytime was not influenced by absolute or relative reduction in SBP and DBP indices. (P > 0.1 for all). CONCLUSION: Catheter-based RDN in resistant hypertensive patients can favorably affect short-term BPV, independent of the level of BP reduction. Further investigation of the effect of RDN on BPV is needed with large randomized trials.