Risk of Parkinson Disease and Secondary Parkinsonism in Myocardial Infarction Survivors.
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ABSTRACT:
SUBMITTER: Sundboll J
PROVIDER: S-EPMC9075091 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMediastinal radiation is associated with increased risk of myocardial infarction (MI) among non-Hodgkin lymphoma (NHL) survivors.ObjectiveTo evaluate how preexisting cardiovascular risk factors (CVRFs) modify the association of mediastinal radiation and MI among a national population of NHL survivors with a range of CVRFs.Material and methodsUsing Danish registries, we identified adults diagnosed with lymphoma 2000-2010. We assessed MI from one year after diagnosis through 2016. We ascertained CVRFs (hypertension, dyslipidemia, and diabetes), vascular disease, and intrinsic heart disease prevalent at lymphoma diagnosis. We used multivariable Cox regression to test the interaction between preexisting CVRFs and receipt of mediastinal radiation on subsequent MI.ResultsAmong 3151 NHL survivors (median age 63, median follow-up 6.5 years), 96 were diagnosed with MI. Before lymphoma, 32% of survivors had ≥1 CVRF. 8.5% of survivors received mediastinal radiation. In multivariable analysis, we found that mediastinal radiation (HR = 1.96; 95% CI = 1.09-3.52), and presence of ≥1 CVRF (HR = 2.71; 95% CI = 1.77-4.15) were associated with an increased risk of MI. Although there was no interaction on the relative scale (p = 0.14), we saw a clinically relevant absolute increase in risk for patients with CVRF from 10-year of MI of 10.5% without radiation to 29.5% for those undergoing radiation.ConclusionPatients with CVRFs have an importantly higher risk of subsequent MI if they have mediastinal radiation. Routine evaluation of CVRFs and optimal treatment of preexisting cardiovascular disease should continue after receiving cancer therapy. In patients with CVRFs, mediastinal radiation should only be given if oncologic benefit clearly outweighs cardiovascular harm.
| S-EPMC9888465 | biostudies-literature
Project description:ObjectiveTo determine the incidence of parkinsonism in community-dwelling older adults without Parkinson disease.MethodsFour parkinsonian signs were assessed with a modified motor portion of the Unified Parkinson's Disease Rating Scale in 2,001 older adults without parkinsonism. We used Cox proportional hazards models to determine the associations of age and sex with incident parkinsonism (2 or more signs). We calculated the number of events per 1,000 person-years of observation in 3 age strata. Next, we investigated several potential risk factors for incident parkinsonism. Then, we examined longitudinal progression of parkinsonism using discrete-time multistate Markov models.ResultsAverage age at baseline was 76.8 years (SD 7.62 years). During an average of 5 years of follow-up, 964/2,001 (48.2%) developed parkinsonism. Age (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.08-1.10) but not male sex (HR 1.06, 95% CI 0.91-1.23) was associated with incident parkinsonism. The incidence of parkinsonism per 1,000 person-years of follow-up was 36.0 for adults <75 years of age, 94.8 for those 75-84, and 160.5 for those 85 years or older. Depressive symptoms, neuroticism, urinary incontinence, sleep complaints, and chronic health conditions were associated with incident parkinsonism. Secondary analyses suggest that risk factors are linked with incident parkinsonism via early motor signs of parkinsonism and cognitive function. Transition modeling suggests that while parkinsonism may fluctuate, it is progressive in most older adults and its risk factors increase the odds of its progression.ConclusionsParkinsonism is common in older adults and increases with age. Identifying modifiable risk factors may decrease the magnitude of this growing public health problem.
| S-EPMC5027813 | biostudies-literature
Project description:PurposePrevious reports suggest that radiation therapy for breast cancer (BC) can cause ischemic heart disease, with the radiation-related risk increasing linearly with mean whole heart dose (MWHD). This study aimed to validate these findings in younger BC patients and to investigate additional risk factors for radiation-related myocardial infarction (MI).Methods and materialsA nested case-control study was conducted within a cohort of BC survivors treated during 1970 to 2009. Cases were 183 patients with MI as their first heart disease after BC. One control per case was selected and matched on age and BC diagnosis date. Information on treatment and cardiovascular risk factors was abstracted from medical and radiation charts. Cardiac doses were estimated for each woman by reconstructing her regimen using modern 3-dimensional computed tomography planning on a typical patient computed tomography scan.ResultsMedian age at BC of cases and controls was 50.2 years (interquartile range, 45.7-54.7). Median time to MI was 13.6 years (interquartile range, 9.9-18.1). Median MWHD was 8.9 Gy (range, 0.3-35.2 Gy). MI rate increased linearly with increasing MWHD (excess rate ratio [ERR] per Gy, 6.4%; 95% confidence interval, 1.3%-16.0%). Patients receiving ≥20 Gy MWHD had a 3.4-fold (95% confidence interval, 1.5-7.6) higher MI rate than unirradiated patients. ERRs were higher for younger women, with borderline significance (ERR<45years, 24.2%/Gy; ERR≥50years, 2.5%/Gy; Pinteraction = .054). Whole heart dose-volume parameters did not modify the dose-response relationship significantly.ConclusionsMI rate after radiation for BC increases linearly with MWHD. Reductions in MWHD are expected to contribute to better cardiovascular health of BC survivors.
| S-EPMC6361769 | biostudies-literature
Project description:ObjectiveTo determine the histopathologic bases for the observed incidence of parkinsonism in families with C9ORF72 expansions, which typically cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia.MethodsDNA was extracted from 377 brains with the histopathologic diagnosis of idiopathic Parkinson disease or related disorders and analyzed for C9ORF72 expansions. ?-Synuclein and p62 immunohistochemistry of the substantia nigra (SN) was undertaken in brains of 17 ALS cases with (C9ORF72+) and 51 without (C9ORF72-) the C9ORF72 expansion.ResultsOnly 1 of 338 cases with pathologically confirmed idiopathic Parkinson disease had a C9ORF72 expansion. Similarly, only 1 of 17 C9ORF72+ brains displayed features suggestive of ?-synucleinopathy. In contrast, p62-positive, TDP-43-negative neuronal cytoplasmic inclusions within the SN were considerably more frequent in C9ORF72+ brain tissue than in the C9ORF72- brains (p = 0.005). Furthermore, there was a more marked loss of dopaminergic neurons in the SN of C9ORF72+ ALS brains than C9ORF72- ALS brains (p = 0.029).ConclusionsSN involvement is common in C9ORF72+ ALS but can be clearly distinguished from Parkinson disease-related mechanisms by the presence of p62-positive inclusions and the absence of ?-synuclein-positive Lewy bodies or Lewy neurites.
| S-EPMC3908460 | biostudies-literature
Project description:ImportanceThe association of premenopausal bilateral oophorectomy with parkinsonism and Parkinson disease (PD) remains controversial.ObjectiveTo assess whether women who underwent premenopausal bilateral oophorectomy were at increased risk of parkinsonism and PD and whether the associations varied by age at oophorectomy and by receipt of estrogen replacement therapy.Design, setting, and participantsThis cohort study used data from a combination of 2 independent cohort studies, the Mayo Clinic Cohort Study of Oophorectomy and Aging 1 and 2, which were based on the Rochester Epidemiology Project medical records-linkage system. A population-based sample of 5499 women from Olmsted County, Minnesota, were included; of those, 2750 women underwent bilateral oophorectomy for a benign indication before spontaneous menopause between January 1, 1950, and December 31, 2007 (oophorectomy cohort), and 2749 age-matched women who did not undergo bilateral oophorectomy were randomly sampled from the general population (reference cohort). Data were analyzed from March 1 to April 30, 2022. The date of oophorectomy was considered the index date for both groups.ExposuresMedical record documentation of bilateral oophorectomy abstracted from a medical records-linkage system (Rochester Epidemiology Project).Main outcomes and measuresIncidence and risk of parkinsonism or PD, with diagnoses confirmed by in-person examination or medical record review.ResultsAmong 5499 participants (median [IQR] age, 45.0 [40.0-48.0] years; 5312 [96.6%] White), 2750 women (2679 White [97.4%]) underwent bilateral oophorectomy at a median age of 45.0 years (IQR, 40.0-48.0 years), and 2749 women (2633 White [95.8%]) with a median age of 45.0 years (IQR, 40.0-48.0 years) at the index date were included in the reference cohort. Bilateral oophorectomy was associated with an increased risk of parkinsonism overall (hazard ratio [HR], 1.59; 95% CI, 1.02-2.46) and in women younger than 43 years at oophorectomy (HR, 7.67; 95% CI, 1.77-33.27). There was a pattern of increasing risk with younger age at the time of oophorectomy using 4 age strata (≥50 years: HR, 1.43 [95% CI, 0.50-4.15]; 46-49 years: HR, 1.55 [95% CI, 0.79-3.07]; 40-45 years: HR, 1.36 [95% CI, 0.64-2.89]; <40 years: HR, 8.82 [95% CI, 1.08-72.00]; P = .02 for trend). The number needed to harm was 53 women overall and 27 women younger than 43 years at the time of oophorectomy. Bilateral oophorectomy was also associated with an increased risk of PD in women younger than 43 years at oophorectomy (HR, 5.00; 95% CI, 1.10-22.70), with a number needed to harm of 48 women. Among women who underwent oophorectomy at 45 years and younger, the risk was lower in women who received estrogen after the procedure and through age 50 years compared with women who did not. For parkinsonism, the HRs were 1.72 (95% CI, 0.54-5.53) vs 2.05 (95% CI, 0.80-5.23); for PD, the HRs were 1.53 (95% CI, 0.29-8.23) vs 2.75 (95% CI, 0.84-9.04). However, the differences were not significant.Conclusions and relevanceIn this study, premenopausal women who underwent bilateral oophorectomy before age 43 years had an increased risk of parkinsonism and PD compared with women who did not undergo bilateral oophorectomy. These findings suggest that a reduction in the practice of prophylactic bilateral oophorectomy in premenopausal women at average risk of ovarian cancer may have substantial benefit for reducing the risk of parkinsonism and PD.
| S-EPMC9606839 | biostudies-literature
Project description:ObjectiveLeucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of Parkinson disease (PD). Several dominantly inherited pathogenic substitutions have been identified in different domains of the Lrrk2 protein. Herein, we characterize the clinical and genetic features associated with Lrrk2 p.R1441C.MethodsWe identified 33 affected and 15 unaffected LRRK2 c.4321C>T (p.R1441C) mutation carriers through an international consortium originating from three continents. The age-specific cumulative incidence of PD was calculated by Kaplan-Meier analysis.ResultsThe clinical presentation of Lrrk2 p.R1441C carriers was similar to sporadic PD and Lrrk2 p.G2019S parkinsonism. The mean age at onset for parkinsonism was 60 years, range 30-79 years; fewer than 20% of the patients had symptoms before the age 50 years, while by 75 years >90% of them had developed symptoms. Haplotype analysis suggests four independent founders for the p.R1441C mutation.ConclusionsThe distribution in age at onset and clinical features in Lrrk2 p.R1441C patients are similar to idiopathic and Lrrk2 p.G2019S parkinsonism. Several independent founders of the p.R1441C substitution suggest this site is prone to recurrent mutagenesis.
| S-EPMC3906630 | biostudies-literature
Project description:Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD).To compare myocardial infarction (MI) and mortality rates between patients with nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort.Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded.Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: ?1 stenosis ?20% but no stenosis ?70%; obstructive CAD: any stenosis ?70% or left main [LM] stenosis ?50%) and distribution (1, 2, or 3 vessel).The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality.Among 37,674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20,899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n?=?8, 95% CI, 0.10%-0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24% (n?=?10, 95% CI, 0.10%-0.40%); 2-vessel nonobstructive CAD, 0.56% (n?=?13, 95% CI, 0.30%-1.00%); 3-vessel nonobstructive CAD, 0.59% (n?=?6, 95% CI, 0.30%-1.30%); 1-vessel obstructive CAD, 1.18% (n?=?101, 95% CI, 1.00%-1.40%); 2-vessel obstructive CAD, 2.18% (n?=?110, 95% CI, 1.80%-2.60%); and 3-vessel or LM obstructive CAD, 2.47% (n?=?137, 95% CI, 2.10%-2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8-5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0-10.5); 3-vessel nonobstructive HR, 4.5 (95% CI, 1.6-12.5); 1-vessel obstructive HR, 9.0 (95% CI, 4.2-19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1-33.7); and 3-vessel or LM obstructive HR, 19.5 (95% CI, 9.9-38.2). One-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there was no significant association between 1- or 2-vessel nonobstructive CAD and mortality, but there were significant associations with mortality for 3-vessel nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3-vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4). Similar associations were noted with the combined outcome.In this cohort of patients undergoing elective coronary angiography, nonobstructive CAD, compared with no apparent CAD, was associated with a significantly greater 1-year risk of MI and all-cause mortality. These findings suggest clinical importance of nonobstructive CAD and warrant further investigation of interventions to improve outcomes among these patients.
| S-EPMC4893304 | biostudies-literature
Project description:BackgroundPrior studies have demonstrated that patients with high-risk acute myocardial infarction (AMI) are less likely to receive guideline-directed medications during hospitalisation. It is unknown if this paradox persists following discharge. We aimed to assess if persistence with guideline-directed medications post discharge varies by patients' risk following AMI.MethodsData were analysed from two prospective, multicentre US AMI registries. The primary outcome was persistence with all prescribed guideline-directed medications (aspirin, β-blockers, statins, angiotensin-antagonists) at 1, 6 and 12 months post discharge. The association between risk and medication persistence post discharge was assessed using multivariable mixed-effect models.ResultsAmong 6434 patients with AMI discharged home, 2824 were considered low-risk, 2014 intermediate-risk and 1596 high-risk for death based upon their Global Registry of Acute Coronary Event (GRACE) 6-month risk score. High-risk was associated with a lower likelihood of receiving all appropriate therapies at discharge compared with low-risk patients (relative risk (RR) 0.90; 95% CI 0.87 to 0.94). At 12 months, the rate of persistence with all prescribed therapies was 61.5%, 57.9% and 45.9% among low-risk, intermediate-risk and high-risk patients, respectively. After multivariable adjustment, high-risk was associated with lower persistence with all prescribed medications (RR 0.87; 95% CI 0.82 to 0.92) over follow-up. Similar associations were seen for individual medications. Over the 5 years of the study, persistence with prescribed therapies post discharge improved modestly among high-risk patients (RR 1.05; 95% CI 1.03 to 1.08 per year).ConclusionsHigh-risk patients with AMI have a lower likelihood of persistently taking prescribed medications post discharge as compared with low-risk patients. Continued efforts are needed to improve the use of guideline-directed medications in high-risk patients.
| S-EPMC4871817 | biostudies-literature
Project description:BackgroundPatients with myocardial infarction (MI) are at increased risk for recurrent cardiovascular events, yet some patients, such as the elderly and those with prior comorbidities, are particularly at the highest risk. Whether these patients benefit from contemporary management is not fully elucidated.MethodsIncluded were consecutive patients with MI who underwent percutaneous coronary intervention (PCI) in a large tertiary medical center. Patients were stratified according to the thrombolysis in myocardial infarction (TIMI) risk score for secondary prevention (TRS2°P) to high (TRS2°P = 3), very high (TRS2°P = 4), or extremely high-risk (TRS2°P = 5-9). Excluded were low and intermediate-risk patients (TRS2°P < 3). Outcomes included 30-day/1-year major adverse cardiac events (MACE) and 1-year mortality. Temporal trends were examined in the early (2004-2010) and late (2011-2016) time-periods.ResultsAmong 2053 patients, 50% were high-risk, 30% very high-risk and 20% extremely high-risk. Extremely high-risk patients were older (age 74 ± 10 year) and had significant comorbidities (chronic kidney disease 68%, prior CABG 40%, heart failure 78%, peripheral artery disease 29%). Drug-eluting stents and potent antiplatelets were more commonly used over time in all risk-strata. Over time, 30-day MACE rates have decreased, mainly attributed to the very high (11.3% to 5.1%, p = .006) and extremely high-risk groups (15.9% to 8.0%, p = .016), but not the high-risk group, with similar quantitative results for 1-year MACE. The rates of 1-year mortality remained unchanged in either group.ConclusionWithin a particularly high-risk cohort of MI patients who underwent PCI, the implementation of guideline-recommended therapies has improved over time, with the highest-risk groups demonstrating the greatest benefit in outcomes.
| S-EPMC8571543 | biostudies-literature
Project description:BackgroundGuidelines recommend using risk stratification tools in acute myocardial infarction (AMI) to assist decision-making. The Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P) has been recently developed to characterize long-term risk in patients with MI.HypothesisWe aimed to assess the TRS-2P in the French Registry of Acute ST Elevation or non-ST elevation MI registries.MethodsWe used data from three 1-month French registries, conducted 5 years apart, from 2005 to 2015, including 13 130 patients with AMI (52% ST-elevation myocardial infarction [STEMI]). Atherothrombotic risk stratification was performed using the TRS-2P score. Patients were divided in to three categories: G1 (low-risk, TRS-2P = 0/1); G2 (intermediate-risk, TRS-2P = 2); and G3 (high-risk, TRS-2P ≥ 3). Baseline characteristics and outcomes were analyzed according to TRS-2P categories.ResultsA total of 12 715 patients (in whom TRS-2P was available) were included. Prevalence of G1, G2, and G3 was 43%, 24%, and 33% respectively. Clinical characteristics and management significantly differed according to TRS-2P categories. TRS-2P successfully defined residual risk of death at 1 year (C-statistic 0.78): 1-year survival was 98% in G1, 94% in G2, and 78.5% in G3 (P < 0.001). Using Cox multivariate analysis, G3 was independently associated with higher risk of death at 1 year (hazard ratio [HR] 4.61; 95% confidence interval [CI]: 3.61-5.89), as G2 (HR 2.08; 95% CI: 1.62-2.65) compared with G1. The score appeared robust and correlated well with mortality in STEMI and NSTEMI populations, as well as in each cohort separately.ConclusionsThe TRS-2P appears to be a robust risk score, identifying patients at high risk after AMI irrespective of the type of MI and historical period.
| S-EPMC6712320 | biostudies-literature