Iqbal Bata

A century of trends in adult human height

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. DOI: http://dx.doi.org/10.7554/eLife.13410.001

Relation of genetic polymorphisms of apolipoprotein E, angiotensin converting enzyme, apolipoprotein B-100, and glycoprotein IIIa and early-onset coronary heart disease.

OBJECTIVE Apolipoprotein E (APOE) E4, apolipoprotein B-100 (APOB) Q3611 allele, the angiotensin converting enzyme (ACE) deletion (D) allele and glycoprotein IIIa (GP3A) P33 mutant allele are reported to predispose to early-onset coronary heart disease (CHD). These associations were not all confirmed in more recent studies. To determine the impact of these alleles on CHD, we examined the prevalence of these mutations in patients presenting with early-onset CHD and compared them to those manifesting CHD later in life. The delayed-onset was considered a sign of longevity and would serve as a comparative group to assess prevalence of the biochemical and genetic risk factors. METHODS 300 patients with a history of myocardial infarction or angina pectoris and angiographically documented CHD were studied. Patients were divided into two groups: group 1 (G1 = 150 patients) presenting with these findings under the age of 50 years; while group 2 (G2 = 150 patients) were patients presenting for the first time over the age of 65 years. Prevalence of the alleles of APOE, APOB, ACE and GP3A was assessed by molecular analysis. An association of any of these genotypes with early onset CHD could lead to a higher prevalence in the younger age group. RESULTS AND CONCLUSIONS None of the suspected alleles namely APOB Q3611 [G1: 10.7% vs. G2: 9.0%, p = 0.57], ACE D (G1: 52.0% vs. G2: 49.7%, p = 0.57), or the GP3A P33 (G1: 17.3% vs. G2: 15.7%; p = 0.58) showed any significant difference between the two groups. Subjects with APOE E4 were more frequent in the younger age group (G1: 18.3% vs. G2: 13.7%; p = 0.047), while APOE E2 was more frequent in G2 (G2: 10.0% vs. G1: 2.7%; p = 0.0002). Multivariate analysis showed an odds ratio of APOE E2 allele in G1 of 0.27 with a confidence interval of 0.10-0.73.

Relation of a Common Mutation in Methylenetetrahydrofolate Reductase to Plasma Homocysteine and Early Onset Coronary Artery Disease

OBJECTIVE In the presence of low serum folate, mutant 5,20-methylenetetrahydrofolate reductase (MTHFR + [A223V/C677T]) in the homozygous state (+/+), may predispose to higher plasma homocysteine (tHct) levels and coronary artery disease (CAD). To determine the impact of this relationship on predisposition to early-onset CAD, we examined the prevalence of the mutation and plasma tHct in patients with early-onset CAD and compared them to patients manifesting CAD later in life. METHODS Three hundred patients with history of acute myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients consisted of two groups: group 1 (G1 = 150 patients) presenting with these findings under age 50; while group 2 (G2 = 150) presented for the first time over age 65 years. Prevalence of the MTHFR+ mutation was assessed by molecular analysis, and plasma tHct and folate were measured. An association of the +/+ genotype with early onset CAD could lead to its higher prevalence in the younger age group. RESULTS There was no significant difference in the frequency of the (+/+) genotype between the two groups (G1: 11.3% vs. G2: 11.3%). However, patients with the (+/+) genotype in both groups had higher tHct when plasma folate was below the mean value (G1: p < 0.0001 while G2: p < 0.01). CONCLUSION The mutant MTHFR genotype was not found to be a determining factor in early-onset CAD. Higher tHct values were obtained in the older age group, which is expected because other studies have shown that tHct levels increase with age. A significant relation was shown between MTHFR genotype and low folate status yielding high tHct levels in those with the (+/+) genotype. As this relation was seen in both groups, although to a lesser extent in the older G2, it does not explain the underlying cause of early-onset CAD.

Relation between butyrylcholinesterase K variant, paraoxonase 1 (PON1) Q and R and apolipoprotein E ϵ4 genes in early-onset coronary artery disease

OBJECTIVES The common K variant of butyrylcholinesterase (BChE-K), an enzyme which metabolizes acetylcholine and organophosphates, has been associated with Alzheimers disease, especially in the presence of the apolipoprotein E epsilon 4 allele (APOE-epsilon 4). Although APOE-epsilon 4 has been associated with the development of coronary artery disease (CAD), an association between the BChE-K variant and CAD has not been explored. Paraoxonase 1 (PON1), located within HDL, is an enzyme which also metabolizes organophosphates and may be antiatherogenic. The R192 variant of PON1 (PON1-R) has been associated with CAD. DESIGN AND METHODS To determine whether BChE-K is also associated with premature CAD, we examined the frequency of BChE-K among patients with early-onset CAD (n = 150; < 50 yr) vs. late-onset CAD (n = 150; > 65 yr) by molecular analysis. We also examined the frequency of the PON1-R allele in both groups, and explored whether there was synergism between BChE-K and APOE-epsilon 4, BChE-K and PON1-R or PON1-R and APOE-epsilon 4. RESULTS The frequency of the BChE-K allele tended to be greater among early-onset CAD patients compared to late-onset CAD patients (41.3% vs. 31.3%; p = 0.07), but without any significant difference between males and females. There was no difference in the prevalence of the PON1-R allele between those with early- or late-onset CAD (46.0% vs. 52.7%; p = 0.25). Twenty-two patients with early-onset CAD had both the BChE-K plus APOE-epsilon 4 alleles (14.7%) compared to 11 late-onset CAD patients (7.3%) (p = 0.04). There was no such association between BChE-K and PON1-R, nor PON1-R and APOE-epsilon 4. CONCLUSIONS Our study suggests that there is a minor association between BChE-K and early-onset CAD, especially in the presence of the APOE-epsilon 4 allele.

Role of the fractalkine receptor CX3CR1 polymorphisms V249I and T280M as risk factors for early‐onset coronary artery disease in patients with no classic risk factors

Objectives. CX3CR1 is a monocyte chemokine receptor and adhesion molecule. Two CX3CR1 mutations, V249I and T280M, reportedly decrease coronary artery disease (CAD) risk independent of established risk factors. An I249 protective effect is attributed to reducing CX3CR1 binding to fractalkine, its ligand. Material and methods. We examined the frequencies of V249I and T280M among early‐onset CAD patients (G1; n = 149; <50 years), late‐onset CAD patients (G2; n = 150; >65 years) and healthy controls (HC; n = 149, 47–93 years) without known CAD risk factors. We compared plasma total cholesterol (TC)/high density lipoprotein‐C (HDL‐C) and apolipoprotein B (APOB)/apolipoprotein AI (APOAI) ratios among the groups and mutation carriers and non‐carriers, and the prevalence of the mutations in G1 and G2 patients with multiple coronary vessel disease (MVD) and myocardial infarction (MI). Results. G1 patients had non‐significantly lower frequencies of I249 versus (vs.) G2 or controls (G1; 51 %, G2: 61 %, controls: 58 %, p = 0.19), with no difference in T280M (p = 0.8). TC/HDL‐C and APOB/APOAI ratios were significantly higher in G1 patients vs. G2 and controls (p<0.0001) independently of either mutation. More G2 patients had MVD than younger ones (p<0.0001); however, more G1 patients were homozygous for V249 compared to G2 patients, who more often had the I249 allele (p<0.02). There was no such association with T280M (p = 0.38). Although more G1 patients had MI, this was not mutation related. Conclusions. There were significantly higher lipid ratios in G1 compared to G2 and HC (G1>G2>HC), but not in mutation prevalence. I249 mutation was associated with MVD in older patients, while V249 homozygosity was associated with the early‐onset CAD. Neither allele affected MI or lipid levels.

Decreasing Mortality from Acute Myocardial Infarctions: Effect of Attack Rates and Case Severity

Mortality from myocardial infarction (MI) has declined in many countries and the reasons for the decline have not been fully quantified. We used the database of the Halifax County MONICA Project to test the hypothesis that the decline of in-hospital mortality from MI can be explained by a trend toward less severe disease as opposed to improved treatment. During the study period 1984-1993, 14,130 people aged 25-74 had been admitted to hospital with suspected MI. Of these, 3774 were diagnosed as definite MI by standardized criteria (480 fatal). For each patient, clinical history, serial cardiac enzymes, and ECG treatment regimen during hospital stay were extracted from patient charts. Survival status 28 days after onset of symptoms was determined. A severity index predicting 28-day case fatality was derived from health status at admission time. During the study period the rate of definite MI in the MONICA target population showed a general downward trend from 221 to 179 per 100,000/year (p = 0.0002). The severity index increased during the observation time (p < 0.0001), predicting 25% higher mortality. Case fatality fluctuated, but showed a marginally significant decline. We conclude that part of the decreased in-hospital mortality from MI is due to lower attack rates. The remainder occurred despite increased case severity and is possibly due to improved in-hospital treatment.

Time from first medical contact to reperfusion in ST elevation myocardial infarction: A Which Early ST Elevation Myocardial Infarction Therapy (WEST) substudy

BACKGROUND Recent research and contemporary ST elevation myocardial infarction guidelines emphasize the importance of prompt reperfusion and have redefined the traditional time to treatment metric to include prehospital paramedical staff as the point of first medical contact. However, an important knowledge gap exists relating to data systematically addressing the impact of arrival at the hospital by ambulance and the delays inherent in transfer from a community hospital to tertiary centres for percutaneous coronary intervention (PCI). METHODS The Which Early ST Elevation Myocardial Infarction Therapy (WEST) study initiated treatment at the point of first medical contact, including prehospital contact. Patients were randomly assigned to receive fibrinolysis with usual care or coupled with mechanical cointervention, or primary PCI. To assess the impact of this strategy on time to treatment, the following randomly assigned patient groups were compared: prehospital versus in-hospital; those arriving at the hospital by ambulance versus ambulatory self transport; and those whose initial hospital care was a community versus PCI centre. RESULTS Of the 328 patients enrolled in the study, 221 received fibrinolysis and 107 received primary PCI. Compared with the in-hospital group, patients who underwent prehospital random assignment (44%, n=145) experienced a 48 min reduction in median (interquartile range) time from symptom onset to first study medication (87 min [65 min to 147 min] versus 135 min [95 min to 186 min]; P<0.001) and a 56 min reduction in time to first balloon inflation (148 min [117 min to 214 min] versus 204 min [166 min to 290 min]; P<0.001). Arrival by ambulance without prehospital random assignment (n=90) incurred a substantial delay from first medical contact to reperfusion (fibrinolysis 76 min [63 min to 105 min] and PCI 160 min [141 min to 212 min]) compared with prehospital random assignment (n=145; fibrinolysis 43 min [33 min to 54 min] and PCI 105 min [90 min to 127 min]) or ambulatory patients (n=93; fibrinolysis 47 min [32 min to 68 min] and PCI 108 min [85 min to 150 min]). Community (n=165) versus PCI hospital (n=163) random assignment was associated with a longer delay from first medical contact to reperfusion: fibrinolysis, 56 min versus 47 min (P=0.008) and primary PCI, 139 min versus 105 min (P=0.001). DISCUSSION Prehospital diagnosis, random assignment and treatment substantially reduced treatment delay with both pharmacological and mechanical reperfusion. Those activating the prehospital medical response system without receiving prehospital random assignment experienced the longest delay from first medical contact to reperfusion, indicating a lost opportunity to enhance ST elevation myocardial infarction patient outcomes.

Trends in event rate and case fatality of patients hospitalized with myocardial infarction between 1984 and 2001.

Between 1984 and 1993, prevalence and case fatality of hospitalized acute myocardial infarction (AMI) had declined in the population of Halifax County. We aimed to determine whether these trends continued into the 21st century by investigating patient characteristics, treatment methods, and fatality for hospital admissions of residents of Halifax County, aged 25-74, during 1984-1989 (period 1), 1990-1993 (period 2), and 1998-2001 (period 3) and diagnosed as AMI that were extracted from databases for the Halifax County MONICA and ICONS (Improving Cardiovascular Outcomes in Nova Scotia) Studies. Trends in patient characteristics and treatment methods were assessed by chi2 statistics. Their association with 28-day fatality was determined by logistic regression. Event rate declined during 1984-1993 but not into 1998-2001 (p = 0.206). Compared with 1990-1993, fewer AMI patients during 1998-2001 were > or = 55 years (73.3% vs. 69.9%), cigarette smokers (49.8% vs. 42.9%), had a history of myocardial infarction (28.9% vs. 24.9%), and had an admission heart rate >100 (34.8% vs. 17.4%). Additionally, more patients had a history of diabetes (22.5% vs. 28.1%). Case fatality declined progressively over the 3 study time periods (16.6%, 13.1%, and 9.4%, respectively). Changes also occurred in prevalence of Killip class 4 status during admission (20.2%, 10.3%, and 13.3%, respectively), use of thrombolysis (9.0%, 30.9, and 32.6%, respectively), and percutaneous coronary intervention (PCI) (4.3%, 11.2%, and 22.4%, respectively) in the different periods. Significant associations were found between case fatality and patient history of diabetes, history of MI, age, elevated admission heart rate, Killip class 4 impairment, thrombolysis, and PCI. The ICONS registry of hospitalized acute myocardial infarctions was used to compare case fatality during 1998-2001 with that reported by the Halifax County MONICA Project for 1984-1993. Whereas the population rate of myocardial infarctions had declined between 1984-1993 but not subsequently, case fatality declined significantly throughout the study period. The continued decline in case fatality is likely explained by changes in patient profile on presentation and medical therapies, including the increased use of thrombolysis and PCI.

Smoking abstinence 1 year after acute coronary syndrome: follow-up from a randomized controlled trial of varenicline in patients admitted to hospital

BACKGROUND: Patients who continue to smoke after acute coronary syndrome are at increased risk of reinfarction and death. We previously found use of varenicline to increase abstinence 24 weeks after acute coronary syndrome; here we report results through 52 weeks. METHODS: The EVITA trial was a multicentre, double-blind, randomized, placebo-controlled trial of varenicline for smoking cessation in patients admitted to hospital with acute coronary syndrome. Participants were randomly assigned (1:1) to receive varenicline or placebo for 12 weeks, in conjunction with low-intensity counselling. Smoking abstinence was assessed via 7-day recall, with biochemical validation using exhaled carbon monoxide. Participants lost to follow-up or withdrawn were assumed to have returned to smoking. RESULTS: Among the 302 participants, abstinence declined over the course of the trial, with 34.4% abstinent 52 weeks after acute coronary syndrome. Compared with placebo, point estimates suggest use of varenicline increased point-prevalence abstinence (39.9% v. 29.1%, difference 10.7%, 95% confidence interval [CI] 0.01% to 21.44%; number needed to treat 10), continuous abstinence (31.1% v. 21.2%, difference 9.9%, 95% CI −0.01% to 19.8%) and reduction in daily cigarette smoking by 50% or greater (57.8% v. 49.7%, difference 8.1%, 95% CI −3.1% to 19.4%). Varenicline and placebo groups had similar occurrence of serious adverse events (24.5% v. 21.9%, risk difference 2.7%, 95% CI −7.3% to 12.6%) and major adverse cardiovascular events (8.6% v. 9.3%, risk difference −0.7%, 95% CI −7.8% to 6.5%). INTERPRETATION: Varenicline was efficacious for smoking cessation in this high-risk patient population. However, 60% of patients who received treatment with varenicline still returned to smoking. Trial registration: ClinicalTrials.gov, no. NCT00794573

COMPONENT TIMES IN PRIMARY PERCUTANEOUS CORONARY INTERVENTION: WHERE DOES THE TIME GO?

Primary percutaneous coronary intervention (PPCI) provided in a timely fashion is the treatment of choice for patients presenting with STEMI. Total ischemic time during STEMI (time from the onset of symptoms to successful reperfusion) is a predictor of adverse outcomes. Several studies have examined